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Purpose: The current stratification system for acute promyelocytic leukemia (APL) is based on the white blood cell (WBC) and the platelet counts (i.e., Sanz score) over the past two decades. However, the borderlines among different risk groups are sometimes ambiguous, and for some patients, early death and relapse remained challenges. Besides, with the evolving of the treatment strategy from all-trans-retinoic acid (ATRA) and chemotherapy to ATRA–arsenic trioxide-based synergistic targeted therapy, the precise risk stratification with molecular markers is needed. Experimental Design: This study performed a systematic analysis of APL genomics and transcriptomics to identify genetic abnormalities in 348 patients mainly from the APL2012 trial (NCT01987297) to illustrate the potential molecular background of Sanz score and further optimize it. The least absolute shrinkage and selection operator algorithm was used to analyze the gene expression in 323 cases to establish a scoring system (i.e., APL9 score). Results: Through combining NRAS mutations, APL9 score, and WBC, 321 cases can be stratified into two groups with significantly different outcomes. The estimated 5-year overall (P = 0.00031), event-free (P < 0.0001), and disease-free (P = 0.001) survival rates in the revised standard-risk group (95.6%, 93.8%, and 98.1%, respectively) were significantly better than those in the revised high-risk group (82.9%, 77.4%, and 88.4%, respectively), which could be validated using The Cancer Genome Atlas dataset. Conclusions: We have proposed a two-category system for improving prognosis in patients with APL. Molecular markers identified in this study may also provide genomic insights into the disease mechanism for improved therapy.

Math and science motivational beliefs are essential in understanding students' science, technology, engineering, and math (STEM) achievement and choices in high school and college. Drawing on the Eccles' expectancy-value theory and Arnett's emerging adulthood framework, this study examined the relations among high school students' motivational beliefs in ninth grade and their STEM course taking and grade point average (GPA) throughout high school as well as their STEM major choice in college. In addition, we examined subgroup differences across (a) gender and (b) college generation status by testing mean-level differences as well as whether these relations between math and science motivational beliefs and STEM outcomes varied by gender and college generation status. Using nationally representative data from the High School Longitudinal Study (N = 14,040; Mage = 14; 51% female students), this study found that adolescents' math and science motivational beliefs at the beginning of high school were positively associated with STEM achievement and course taking throughout high school and college major choices 7 years later. The results showed that female and first-generation college students had lower math and science self-concept of ability and were less likely to pursue a STEM major in college. However, in most cases, the relations among indicators did not vary by gender and college generation status. This study provided insights for policymakers and practitioners that gender and college generation gaps in STEM are evident at least by the beginning of high school and carry forward to their STEM college choices. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Background Cushing’s syndrome has been described as a complex endocrine disorder characterized with high cortisol concentration. Correct and early diagnosis of Cushing’s syndrome is challenging. According to the latest guideline, bilateral inferior petrosal sinus sampling (BIPSS) is considered to be the gold standard for the differential diagnosis. However, in some unusual cases, this method may be false positive. Here, we presented a rare case of orbital neuroendocrine tumor secreting adrenocorticotrophic hormone with false positive inferior petrosal sinus sampling. Case presentation A 48-year-old woman was admitted to West China Hospital of Sichuan University, presenting with fatigue, whole body edema for 1 year, alopecia and skin pigmentation for 5 months. Hormonal profiles including plasma cortisol and adrenocorticotrophic hormone (ACTH) measurements and low-dose dexamethasone inhibition test suggested that the patient had Cushing’s syndrome. However, during tumor location phase, the results of high-dose dexamethasone inhibition test (HDDST) contradicted desmopressin (DDAVP) stimulation test. Thus, BIPSS was employed, and its results indicated a pituitary origin. Interestingly, MRI of sellar region showed an innocent pituitary but caught a serendipitous lesion in the lateral rectus muscle of left eye, which was later proved to be an orbital neuroendocrine tumor secreting ACTH by pathological and immunohistochemical results. ACTH level of the patients was Conclusion We reported a rare case of endogenous Cushing’s syndrome due to ectopic ACTH secreting from an orbital neuroendocrine tumor. This unique case of orbital EAS suggests that orbital venous blood backflow, owning to abnormal anatomic structures, may possibly lead to false positive BIPSS results.

Corticospinal neurons (CSNs) undertake direct cortical outputs to the spinal cord and innervate the upper limb through the brachial plexus. Our previous study has shown that the contralateral middle trunk transfer to the paralyzed upper extremity due to cerebral injury can reconstruct the functional cerebral cortex and improve the function of the paralyzed upper extremity. To interpret the cortical reconstruction and the motor improvement after the middle trunk transfer, we explored the distribution of CSNs connecting to the middle, upper, and lower trunk of the brachial plexus by retrograde trans-neuronal tracing using pseudorabies virus (PRV-EGFP or PRV-mRFP). We show that, rather than an individual specific area, these CSNs labelled by each trunk of the brachial plexus were widespread and mainly assembled within the primary motor cortex (M1), secondary motor cortex (M2), primary somatosensory cortex (S1), and slightly within the secondary somatosensory cortex (S2). The three trunk-labelled CSNs were intermingled in these cortices, and mostly connected to more than two trunks, especially the middle trunk-labelled CSNs with higher proportion of co-labelled neurons. Our findings revealed the distribution features of CSNs connecting to the adjacent spinal nerves that innervate the upper limb, which can improve our understanding of the corticospinal circuits associated with motor improvement and the functional cortical reconstruction after the middle trunk transfer.

Carpal tunnel syndrome (CTS) is a most common peripheral nerve entrapment neuropathy characterized by sensorimotor deficits in median nerve innervated digits. Block-design task-related functional magnetic resonance imaging (fMRI) studies have been used to investigate CTS-related neuroplasticity in the primary somatosensory cortices. However, considering the persistence of digital paresthesia syndrome caused by median nerve entrapment, spontaneous neuronal activity might provide a better understanding of CTS-related neuroplasticity, which remains unexplored. The present study aimed to investigate both local and extensive spontaneous neuronal activities with resting-state fMRI. A total of 28 bilateral CTS patients and 24 normal controls were recruited, and metrics, including amplitude of low-frequency fluctuation (ALFF) and voxel-wise functional connectivity (FC), were used to explore synaptic activity at different spatial scales. Correlations with clinical measures were further investigated by linear regression. Decreased amplitudes of low-frequency fluctuation were observed in the bilateral primary sensory cortex (SI) and secondary sensory cortex (SII) in CTS patients (AlphaSim corrected P < .05). This was found to be negatively related to the sensory thresholds of corresponding median nerve innervated fingers. In the voxel-wise FC analysis, with predefined seed regions of interest in the bilateral SI and primary motor cortex, we observed decreased interhemispheric and increased intrahemispheric FC. Additionally, both interhemispheric and intrahemispheric FC were found to be significantly correlated with the mean ALFF.

IntroductionEarly adolescence is a developmental period in which peer victimization, bullying, relational aggression, and social exclusion are particularly prominent. As these behaviors have long-term implications for children, in this study, we investigated early variations of prosocial behaviors as one of the critical precedents that shape youth's subsequent peer relational outcomes. Specifically, we identified different profiles of prosocial behaviors in middle childhood (Grade 4) and related these profiles to peer relationships in early adolescence (Grade 6).MethodUsing longitudinal data from the NICHD Study of Early Child Care and Youth Development (N=914; 52% girls), a three-step latent profile analysis was conducted on Grade 4 prosocial behaviors, which were then related to Grade 6 teacher- and student-rated peer relationships (e.g., relational aggression).ResultsFour patterns of prosocial behaviors emerged: low prosocial (18%), high prosocial (67%), primarily friendly (8%), and primarily kind (7%). These four patterns of prosocial behaviors were differentially related to later problematic peer relationships: Low prosocial youth demonstrated the most problematic peer relationships (Mdiff=0.36-0.93, all p&nbsp

Spastic arm paralysis after central neurological injury has a long-term effect on the patient's quality of life. Effective neurosurgical treatment for this dysfunction has been described in our previous studies. It is of great significance to determine a set of unified and concise clinical standards for motor function grading in the neurosurgical treatment and management.We first conducted a retrospective study that included 51 hemiplegic patients from the Neurosurgery and Microsurgery outpatient database of Huashan Hospital. The neurosurgeons cooperated with rehabilitation experts to design and administer the new rating system (Hua-Shan Grading of Upper Extremity, H-S grading) after analyzing the scale scores and video records of these patients. We then randomly enrolled 64 patients with unilateral spastic arm paralysis after stroke or brain trauma. The Fugl-Meyer Assessment, the Ashworth scale and the new grading system were applied and analyzed to evaluate the participants' motor function.Based on rehabilitation medicine scales and long-term follow-up, a feasible and concise grading system was applied that was based on the patients' characteristics and the examination experiences of neurosurgeons and rehabilitation experts in clinical practice. This method could effectively grade upper extremity motor function, usually in 3-5 minutes. A significant correlation was found between H-S grading and the Fugl-Meyer score by the Spearman test (r = .937, P.01). The mean difference between any two levels of the new grading system was significant (P.05). And good test-retest reliability, the Cronbach's alpha coefficient and the validity indices were presented. In addition, it was more sensitive to motor function compared with the Ashworth scale.As a supplement to the classic scales, H-S grading was developed in the area of spastic hemiplegia treatment. It is standardized and simplified for patients in the chronic stage after central neurological injury.

OBJECTIVEContralateral C7 (CC7) nerve root has been used as a donor nerve for targeted neurotization in the treatment of total brachial plexus palsy (TBPP). The authors aimed to study the contribution of C7 to the innervation of specific upper-limb muscles and to explore the utility of C7 nerve root as a recipient nerve in the management of TBPP.METHODSThis was a 2-part investigation. 1) Anatomical study: the C7 nerve root was dissected and its individual branches were traced to the muscles in 5 embalmed adult cadavers bilaterally. 2) Clinical series: 6 patients with TBPP underwent CC7 nerve transfer to the middle trunk of the injured side. Outcomes were evaluated with the modified Medical Research Council scale and electromyography studies.RESULTSIn the anatomical study there were consistent and predominantly C7-derived nerve fibers in the lateral pectoral, thoracodorsal, and radial nerves. There was a minor contribution from C7 to the long thoracic nerve. The average distance from the C7 nerve root to the lateral pectoral nerve entry point of the pectoralis major was the shortest, at 10.3 ± 1.4 cm. In the clinical series the patients had been followed for a mean time of 30.8 ± 5.3 months postoperatively. At the latest follow-up, 5 of 6 patients regained M3 or higher power for shoulder adduction and elbow extension. Two patients regained M3 wrist extension. All regained some wrist and finger extension, but muscle strength was poor. Compound muscle action potentials were recorded from the pectoralis major at a mean follow-up of 6.7 ± 0.8 months; from the latissimus dorsi at 9.3 ± 1.4 months; from the triceps at 11.5 ± 1.4 months; from the wrist extensors at 17.2 ± 1.5 months; from the flexor carpi radialis at 17.0 ± 1.1 months; and from the digital extensors at 22.8 ± 2.0 months. The average sensory recovery of the index finger was S2. Transient paresthesia in the hand on the donor side, which resolved within 6 months postoperatively, was reported by all patients.CONCLUSIONSThe C7 nerve root contributes consistently to the lateral pectoral nerve, the thoracodorsal nerve, and long head of the triceps branch of the radial nerve. CC7 to C7 nerve transfer is a reconstructive option in the overall management plan for TBPP. It was safe and effective in restoring shoulder adduction and elbow extension in this patient series. However, recoveries of wrist and finger extensions are poor.

BACKGROUND Central neurological injury (CNI) is a major contributor to physical disability that affects both adults and children all over the world. The main sequelae of chronic stage CNI are spasticity, paresis of specific muscles, and poor selective motor control. Here, we apply the concept of contralateral peripheral neurotization in spasticity releasing and motor function restoration of the affected upper extremity. OBJECTIVE A clinical investigation was performed to verify the clinical efficacy of contralateral C7 neurotization for rescuing the affected upper extremity after CNI. METHODS In the present study, 6 adult hemiplegia patients received the nerve transfer surgery of contralateral C7 to C7 of the affected side. Another 6 patients with matched pathological and demographic status were assigned to the control group that received rehabilitation only. During the 2-year follow-up, muscle strength of bilateral upper extremities was assessed. The Modified Ashworth Scale and Fugl-Meyer Assessment Scale were used for evaluating spasticity and functional use of the affected upper extremity, respectively. RESULTS Both flexor spasticity release and motor functional improvements were observed in the affected upper extremity in all 6 patients who had surgery. The muscle strength of the extensor muscles and the motor control of the affected upper extremity improved significantly. There was no permanent loss of sensorimotor function of the unaffected upper extremity. CONCLUSION This contralateral C7 neurotization approach may open a door to promote functional recovery of upper extremity paralysis after CNI.

Objective There is little information available regarding Chinese patients with Hodgkin lymphoma (HL). We analyzed the clinical features, outcome, and prognostic factors of Chinese patients with HL, aiming to establish a new risk model for better risk-adapted therapeutic strategy. Patients and Methods Patients with newly diagnosed HL at 4 medical centers from January 2000 to August 2014 were recruited. Results A total of 150 patients were reviewed. The median age was 30 years (range, 15-91 years). At completion of initial therapy, 73.65% of patients achieved complete remission. The 5-year event-free survival (EFS) of the entire cohort was 61.1%, the overall survival was 84.7%, and the disease-free survival was 78.8%. B symptoms, extranodal involvement, and International Prognostic Score ≥ 3 remained as independent prognostic factors of EFS. Patients who failed to reach complete remission on interim positron emission tomography/computed tomography or computed tomography had a significantly worse outcome than those who did. A new risk model incorporating traditional risk factors and interim response stratified patients into 3 classes, with a 5-year EFS of 100%, 83.1%, and 33.1%, respectively ( P Conclusions General clinical features were comparable with those of Western patients, whereas therapeutic outcomes were slightly inferior. The novel risk assessment model showed potential as a more powerful prognostic tool by identifying 3 subsets of patients with significantly distinct outcomes, which warrants further validations.

The present study was performed in China to compare the efficacy and safety of an advanced wound dressing made of crystalline cellulose (Veloderm) to a conventional treatment of three Vaseline gauzes in the management of skin donor sites of burns or reconstructive plastic surgery. In this prospective, multicenter, open-labeled, randomized clinical trial performed in three Chinese burn centers in China, 96 patients who required autologous split skin graft were randomized into either the test (Veloderm) group or the control (Vaseline gauze) group. Average healing times in the test group and in the control group were 8.40±2.90 and 8.92±2.58 days, respectively, with median values of 7.00 and 8.00 days, respectively: the difference between two groups was statistically significant (P=.045). Scores for exudates, pain intensity, and peripheral erythema showed no difference between the groups; however, composite scores of three variables on day 10 postoperatively was significantly lower in the test group (0.00±0.00 vs. 0.13±0.49; P = .043). The need for a dressing change was also significantly lower in the test group (12.5 vs. 31.25%; P = .036). Veloderm is a safe and effective dressing that may offer some advantages over the traditional application of Vaseline gauze in the management of donor sites in burn or reconstructive plastic surgery patients.

BACKGROUND A functional vestibular system is a prerequisite for motion sickness (MS) to occur. The otolithic organs (saccule and utricle) are currently considered to be important in the pathogenesis of MS. Recent investigations have demonstrated that the ocular vestibular evoked myogenic potentials (oVEMP) test is an objective evaluation of utricular function. To date, there is no functional guide that can serve as a diagnostic tool for individual susceptibility to MS. Therefore, we investigated the link between oVEMP and MS susceptibility. METHOD The oVEMP test was performed on 31 MS susceptible and 23 nonsusceptible individuals. MS susceptibility was determined by self-declaration and by using the MS susceptibility questionnaire (MSSQ) and the Hamilton Anxiety Scale (HAS). RESULTS Bilateral oVEMP responses were obtained in all subjects. HAS and MSSQ scores between the susceptible and nonsusceptible group were 18.27 +/- 5.23 vs. 2.34 +/- 1.21 and 28.12 +/- 6.53 vs. 2.34 +/- 1.45, respectively. Statistically significant differences in MSSQ and HAS scores were found between the MS susceptible and nonsusceptible groups. No differences were found between MS susceptible and nonsusceptible subjects in N10 and P15 wave latencies, N10-P15 interval, or peak-to-peak N10-P15 amplitude. However, there was a trend toward greater asymmetry ratio in the MS susceptible group than in the MS nonsusceptible group (18.55 +/- 10.24% vs. 13.25 +/- 9.47%), although statistical significance was not reached. DISCUSSION It appears that no relation exists between oVEMP results and MS susceptibility. Nevertheless, the differences in the asymmetry ratios of oVEMP interpeak amplitude between the two groups revealed a trend toward marginal statistical significance.

Objective: To investigate the gene mutation and the clinical features of CSF3R, SETBP1 and SRSF2 in chronic neutrophilic leukemia (CNL) and chronic myelomonocytic leukemia (CMML) patients. Method: Sequence analysis of CSF3R, SETBP1 and SRSF2 were performed in 10 CNL and 56 CMML patients whose clinical features were also studied. Result: Among 10 CNL patients, 8(8/10, 80%) patients had CSF3R mutations and 7(7/8, 87.5%) of them were with CSF3R T618I. In 56 cases of patients with CMML, SRSF2 mutations were found in 14(14/56,25%), CSF3R in 4(4/56,7.1%) and SETBP1 in 3(3/56, 5.3%) patients. In CMML, compared to wild-type(wt) SRSF2 patients, SRSF2 mutated patients appeared to be more possible with SETBP1 mutations [1/14(7.1%) vs. 2/42(4.8%), P>0.05], less possible with CSF3R mutation [0/14(0%) vs. 4/42(9.5%), P Conclusion: The majority of patients with WHO-defined CNL have oncogenic mutations in CSF3R and the T618I mutation type is a highly sensitive and specific molecular marker of the disease. While mutations of SRSF2 are common in CMML and may be of prognostic significance. As a non-specific molecular marker, SETBP1 was found in CNL, CMML and other blood cancers, which have poor prognosis. Disclosures No relevant conflicts of interest to declare.

INTRODUCTION Excellent vestibular function (including utricular function) is important for pilots to maintain correct spatial orientation during flight. Vestibular-evoked myogenic potential (VEMP) recorded from extraocular muscles, the so-called ocular VEMP (oVEMP), can be used to evaluate utricular function. However, oVEMP has not been applied to pilots because of lack of reliable normative data. Hence, this study is designed to establish preliminary normative data for oVEMP induced by air-conducted sound in pilots and student pilots. METHODS There were 62 healthy student pilots (30 male and 32 age-matched female) and 31 healthy male fighter pilots who were recruited as study participants. During binaural air-conducted sound stimulation oVEMP was recorded bilaterally. The latencies of nI and pI, nI-pI interval, peak-to-peak nI-pI amplitude, and asymmetry ratio (AR) of oVEMP in all participants were collected. Meanwhile, the effects of gender and age on oVEMP were also investigated. RESULTS The latencies of nI and pI, nI-pI interval, nI-pI interpeak amplitude, and AR of oVEMP in all participants were 10.35 +/- 0.66 ms, 15.18 +/- 1.07 ms, 4.75 +/- 0.99 ms, 6.75 +/- 4.13 microV, and 13.22 +/- 9.13%, respectively. No significant difference existed between male student pilots and male pilots in terms of oVEMP parameters. The only significant difference was the nI-pI amplitude between age-matched male and female student pilots: 6.96 +/- 3.85 microV for male student pilots and 5.47 +/- 3.10 microV for female student pilots. CONCLUSIONS oVEMP should be interpreted with the AR rather than raw amplitude itself. Each institution should determine its own normal values.

Modern intensive chemotherapy regimens have improved the prognosis for adult patients with acute lymphocytic leukemia (ALL). With these regimens, the complete response (CR) rates are approximately 75% and long-term disease-free survival (DFS) rates are about 20-35%. For patients with high-risk ALL, DFS rates are only 20% or less. Hyper-CVAD regimen is effective in ALL and aggressive non-Hodgkin lymphomas (NHL) with increased CR rates and DFS rates. Between June 2002 and October 2006, 53 consecutive adult patients with newly diagnosed adult ALL were treated with Hyper-CVAD regimen for six to eight cycles. The alternating courses were given every 3-4 weeks or earlier if count recovery occurred. CR rates of 73.6% were achieved in 39 patients, the estimated 2-year survival rate was 82.9% and the estimated 2-year event-free survival (EFS) rate was 87.3%. Side effects were as expected, mostly attributed to myelosuppression. Analysis of prognostic factors suggested that some previously well-established poor prognostic factors such as the degree of leukocytosis and central nervous system (CNS) or testicular involvement were less important with this dose-intensive regimen. However, patients with mediastinal disease had lower CR rates (P

Recent studies have shown that Janus tyrosine kinase 2 (JAK2) V617F mutation is found in nearly all patients with polycythemia vera (PV) and underlie the basis of PV molecular pathogenesis. Moreover, JAK2 V617F patients with essential thrombocythemia (ET) have been found to have some clinical features similar to PV. To determine whether the same is true in a different Chinese patient population, we employed Allele-specific polymerase chain reaction in combination with sequence analysis to investigate the point mutation in a series of Chinese patients with hematological malignancies. A total of 99 Chinese myeloproliferative disorder patients and 120 additional patients with acute myeloid leukemia, acute lymphoblastic leukemia and myelodysplastic syndromes were studied. The V617F mutation was detected in genomic DNA of peripheral blood samples of 16 of 23 PV patients (69.6%), 21 of 45 ET patients (46.7%) and 3 of 8 patients with idiopathic myelofibrosis (37.5%). There were striking differences in clinical features such as hemoglobin, hematocrit and neutrophils percentages between V617F positive and negative patients with ET. Hence, our data support the idea that JAK2 V617F mutation divides ET patients into two subtypes, with the V617F positive group showing phenotypic similar to that of PV.

// Jianyong Li 1,2,* , Yaoyu Chen 1,2,* , Yu Zhu 1,2 , Jianfeng Zhou 3 , Yanli Xu 4 , Yan Li 5 , Kang Yu 6 , Ling Pan 7 , Jianmin Wang 8 , Jiahua Ding 9 , Jian Gu 10 , Shanhua Zhou 11 , Jinning Shi 12 , Ming Hong 1,2 , Ji Xu 1,2 , Liangqin Pan 1,2 , Limin Duan 1,2 , Run Zhang 1,2 , Sujiang Zhang 1,2 , Huayuan Zhu 1,2 , Hua Lu 1,2 , Peng Liu 1,2 , Hongxia Qiu 1,2 , Hanxin Wu 1,2 and Sixuan Qian 1,2 1 First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China 2 Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China 3 Tongji Hospital affiliated to Tongji medical college of Huazhong University of Science and Technology, Wuhan, China 4 Nanjing Hospital Affiliated to Nanjing Medical University, Nanjing, China 5 First Affiliated Hospital of China Medical University, Shenyang, China 6 First Affiliated Hospital of Wenzhou Medical College, Wenzhou, China 7 West China Hospital of Sichuan University, Chengdu, China 8 Changhai Hospital, Secondary Military Medical University, Shanghai, China 9 Zhongda Hospital, Southeast University, Nanjing, China 10 Clinic Medical College of Yangzhou University, Yangzhou, China 11 Zhongshan Hospital, Fudan University, Shanghai, China 12 Jiangning Hospital, Nanjing, China * The authors contributed equally to this work Correspondence: Sixuan Qian, email: // Keywords : D-CAG, elderly patients, AML Received : December 01, 2014 Accepted : January 13, 2015 Published : January 31, 2015 Abstract Purpose: This prospective phase II, open label, study was designed to assess the efficacy and safety of D-CAG induction treatment for elderly patients with newly diagnosed AML. Experimental Design: All patients in this study were treated with decitabine of 15 mg/m 2 for 5 days and G-CSF for priming, in combination with cytarabine of 10-mg/m 2 q12h for 7 days and aclarubicin of 10 mg/day for 4 days (D-CAG). Results: Among 85 evaluable patients, overall response rate (ORR) and complete remission (CR) were 82.4% and 64.7%, respectively, after 1 cycle of therapy. The ORR in patients aged

To investigate SRSF2 mutations in patients with chronic myelomonocytic leukemia (CMML) and the clinical characteristics of patients with SRSF2 mutants.In this study, the frequency of SRSF2 mutation in a cohort of 20 patients with CMML was detected by polymerase chain reaction (PCR) followed by direct sequencing to couple with their clinical features.Of 20 patients, 4 patients were found harboring SRSF2 mutations, including 2 P95L, 1 P95H and 1 P95R point mutations. There were no significantly statistical differences in terms of their clinical characteristics between mutant and wild type group.SRSF2 mutation was not frequently occurred in CMML patients and might associated with poor prognosis. It might be a practically diagnostic maker and therapeutic target in CMML.

The optimal post-remission therapy (PRT) for acute myeloid leukemia (AML) remains uncertain. We reported 32 AML patients in first complete remission (CR1) undergoing autologous hematopoietic stem cell transplantation (ASCT) with a characteristic conditioning regimen, termed I-Bu, based on high-dose idarubicin plus busulfan, which considerably strengthened antileukemic activity. Most patients were in better or intermediate-risk group except that cytogenetic or molecular risk information was missing for 18.7 % of the patients. Unpurged peripheral blood stem cells were used in all the cases. The adverse effects were mild and reversible. Only one case of transplant-related mortality was observed. All the patients in this study acquired hematopoietic reconstitution after ASCT. After a median follow-up of 30 (6–119) months, 24 patients (75.0 %) were alive in which 20 (62.5 %) patients were in continuous CR. There were 11 (34.4 %) patients who relapsed after HSCT. Cumulative relapse probability was about 40 % after 24 months. Median OS and DFS have not been reached. Patients in the better and intermediate-risk group had different clinical outcomes, but the differences were not statistically significant. ASCT with I-Bu regimen is possibly promising PRT for better and intermediate-risk AML patients in CR1.

This study was aimed to evaluate the efficacy and safety of dasatinib in BCR/ABL positive leukemia patients with primary or secondary resistance to imatinib. 27 patients with primary or secondary imatinib-resistant chronic myelogenous leukemia (CML) or Philadelphia chromosome positive acute lymphocytic leukemia (Ph(+) ALL) received 100 - 140 mg/d dasatinib orally. Their overall survival and tolerance were evaluated. The results showed that the median duration of dasatinib therapy was 8 (1-66) months in the 27 imatinib-resistant BCR/ABL positive leukemia cases, with a median follow-up of 54 (3-75) months. After the dasatinib treatment, 88.8% of all the 27 cases achieved complete hematologic response (CHR), 29.6% of them achieved major cytogenetic response (mCyR), 37% of all achieved complete cytogenetic response (CCyR) and 18.5% cases achieved major molecular response (MMR). Patients who received dasatinib in progress of disease (CML-AP, CML-BC and bone marrow relapse Ph(+) ALL) had a lower CCyR rate than those in stable disease (CML-CP and bone marrow remission Ph(+) ALL) (P = 0.0377), and 3 - 4 grade adverse events occurred more frequently in progress of disease than that in stable disease. Overall survival of the patients who achieved CCyR after dasatinib therapy was statistically longer than those who did not achieve CCyR (63 m vs 9 m, P = 0.0126). The most common grade 3 - 4 adverse events during dasatinib therapy including hematology events such as thrombocytopenia (51.8%), neutropenia (48.1%), anemia (33.3%), and non-hematologic events such as pleural effusion (18.5%), pulmonary infection (18.5%), pericardial effusion (11.1%). The 3-4 grade adverse events occurred within 12 months from dasatinib therapy, and were mainly observed in patients with progress of disease. It is concluded that dasatinib is an effective drug in imatinib-resistant BCR/ABL positive leukemia patients, the better curative effect and better tolerance has been observed in patients who received dasatinib in stable disease.

Therapy-related myelodysplastic syndromes and acute myelogenous leukemia comprise a poor-risk subset of myelodysplastic syndromes and acute myelogenous leukemia. Large-scale mutation profiling efforts in de novo myelodysplastic syndromes have identified mutations that correlate with clinical features, but such mutations have not been investigated in therapy-related myelodysplastic syndromes and acute myelogenous leukemia. Genomic DNA from 38 patient samples were subjected to high throughput polymerase chain reaction and sequenced for TP53, TET2, DNMT3A, ASXL1, IDH1, IDH2, EZH2, EED, SUZ12, RBBP4, SRSF2, U2AF35, and SF3B1. We identified somatic mutations in 16 of 38 (42%) patients. TP53 mutations were the most common lesion, detected in 8 of 38 (21%) patients, followed by TET2 in 4 of 38 (10.5%). Cases with a TP53 mutation or loss of the TP53 locus had a worse overall survival compared to those with wild-type TP53 (8.8 vs. 37.4 months; P=0.0035).

This study was aimed to detect the peripheral blood serum neopterin (Npt) level in the patients with hemophagocytic lymphohistiocytosis (HLH) and to explore its significance in HLH. The enzyme-linked immunosorbent assay (ELISA) was applied to detect the serum Npt level and sCD25 level in 20 HLH patients before and after treatment and 15 healthy controls. The results indicated that the serum Npt and sCD25 levels in HLH patients were significantly higher than those in healthy controls (P0.0001). The serum Npt and sCD25 levels in the HLH group decreased significantly after treatment, respectively (P0.0001). The correlation analysis of Npt with sCD25 before and after treatment showed that they had significant correlation (r = 0.81, P0.05 before treatment; r = 0.65, P0.05 after treatment). Meanwhile, the level of serum Npt and ferritin had a significant correlation in newly diagnosed HLH patients (r = 0.55, P0.05). It is concluded that the serum Npt may play an important role in the HLH pathogenesis, the enhancement of Npt levels has an important significance for diagnosis and evaluation for HLH.

This study was purposed to investigate the incidence of mixed lineage leukemia (MLL) gene rearrangement and partner gene types as well as the clinical features and prognosis of acute leukemia (AL) with this rearrangement through detection in adult AL using combination of 3 techniques, and to evaluate the clinical value of this combination detection. The MLL gene rearrangement in 183 cases of adult AL was detected by combination of conventional cytogenetics, split signal FISH and multiplex nested PCR. The results showed that the incidence of MLL rearrangements in adult patients with AL was low (8.2%), and MLL-AF4 fusion gene was most common and predominant in acute lymphoblastic leukemia (ALL), while the MLL-AF6 and MLL-AF9 were most frequent in acute myeloid leukemia (AML). Extramedullary involvements were found in 40% of MLL-rearranged AL patients, and 33.3% of patients with MLL-rearranged AL reached to complete remission within 30 days during induction chemotherapy. In addition, in this cohort of MLL-rearranged adult AL patients, the 3-month relapse rate and 6-month overall survival rate were 50.0% and 50.0% respectively. It is concluded that the rate of missed diagnosis of CC technique for patients with MLL-rearranged AL reached to 60% in this study, while the combination of CC, FISH and multiplex nested PCR has been confirmed to have important significance for evaluating prognosis and conducting clinical therapy of patients with MLL-rearranged AL.

MicroRNAs (miRNAs) are of great importance in pathogenesis, diagnosis and prognosis of acute leukemia (AL). We studied five AL-related miRNAs to confirm the significance of these miRNAs in AL. Samples tested included acute myeloid leukemia (AML), 107 cases; acute lymphoblastic leukemia (ALL), 40 cases. Five AL-related miRNAs: miR-128, let-7b, miR-223, miR-181a and miR-155 expression were detected by qRT-PCR. Analysis showed that miRNA-128 expression was significantly higher in ALL (P

The purpose of this study was to identify point mutation of the isocitrate dehydrogenase gene (IDH1 and IDH2) in patients with acute myeloid leukemia(AML) and its clinical significance. 90 de novo AML patients were selected for this study, the genomic DNA was served as template, the exon4 of IDH1 and IDH2 were amplified respectively. The IDH mutation was detected by using directly sequencing method for PCR product. The results indicated that among 90 de novo AML patients, 4 patients (4.4%) showed the IDH1 gene mutation positive, and 7(7.8%) patients showed IDH2 gene mutation positive. None was found harboring both mutations, the overall rate of mutation positive of them was 12.2%. In the AML patients with IDH gene mutation positive, the rate of normal karyotype was 72.7%, which was significantly higher than that in abnormality karyotype. The CR rate in mutation positive patients was 72.7%, which seemed as if higher than that in mutation negative patients, but without statistical significance. The mutation disappeared when the patients gained CR, and reappeared in same loci after relapse occurred. It is concluded that the IDH gene point mutation appears in normal karyotype patients, especially in patients combined with NPM1 gene mutation. The IDH gene mutation may be an important target for therapy and evaluating clinical prognosis of patients with normal karyotype.

Purpose The optimal treatment for cubital tunnel syndrome is widely debated. The purpose of this study is to describe the technique of an endoscopic-assisted ulnar nerve decompression using carbon dioxide insufflation in association with subcutaneous anterior transposition and to assess the success or failure of the method of treatment. Methods In all, 8 male and 4 female patients with an average age of 42 years (range, 25-56) who presented signs, symptoms, and abnormal neurophysiological studies of cubital tunnel syndrome were recruited in the retrospective study. Between August 2008 and June 2009, they were operated on using a 0-degree lens endoscope. Preoperatively, they were classified according to the Dellon scale, and the Bishop rating system was used to evaluate the postoperative outcomes. Results Preoperatively, 5 patients were rated as mild, another 5 as moderate, and the remaining 2 as severe. The average length of the incision was 15 ± 3 mm, the mean length of the ulnar nerve decompression was 18 ± 2 cm, and the whole duration of surgery (skin to skin) lasted 30 ± 5 minutes. The endoscopic-assisted cubital tunnel release under carbon dioxide insufflation and subcutaneous anterior transposition surgeries in all patients were performed with no difficulty. All the patients had improvement in symptoms of cubital tunnel syndrome and 10 of 12 patients scored excellent according to the modified Bishop Rating System at a minimum of 1 year after surgery. Conclusions Endoscopy-assisted cubital tunnel release under carbon dioxide insufflation demonstrated similar results compared with conventional open surgeries, besides, it may avoid problems such as long incision, painful scarring, and have additional advantages of providing an extended endoscopic view, which is safe and mini-invasive with favorable results in a 12-month follow-up.

This study was purposed to investigate the mutational status of DNA methyltransferase (DNMT3a) gene and the clinical features of AML patients with DNMT3a mutations. Using PCR combined with directly sequencing, the somatic mutations of DNMT3a involving residue of amino acid 882 were detected in 77 AML patients. Furthermore, the clinical features of these patients were also studied. The results showed that the DNMT3a mutation were detected in 7 out of 59 patients with de novo AML (11.9%), which included 4 patients with DNMT3a R882C, 2 patients with DNMT3a R882H and 1 patient with DNMT3a Y874C. Morphology examination indicated that 2 patients were M(2), 1 patient was M(4) and 4 patients were M(5). Cytogenetic analysis revealed that karyotype in 5 out of 7 patients with DNMT3a mutation were normal. In total of 27 patients with normal karyotype 5 patients (22.7%) were found harboring DNMT3a mutation, while no DNMT3a mutation was found in 21 patients with abnormal karyotype. The mutation rate in patients with positive CEBPA was obviously higher than that in patients with negative CEBPA (p = 0.002). Immunophenotype analysis showed that 4 patients (4/7, 57.1%) with DNMT3a mutation expressed lymphoid antigens including CD4 or/and CD7. There were no statistical significance in age, gender, blast cells of bone marrow, white blood cell and platelet counts, hemoglobin level, ratio of CR, mutations of FLT3-ITD, NPM1 and c-kit between patients with DNMT3a mutation and patients with wild DNMT3a (p0.05). It is concluded that the DNMT3a mutations are more prevalent in AML patients with normal karyotype accompanying with positive NPM1 and/or CEBPA mutation, the role of DNMT3a mutation in AML prognosis needs to be further studied.

This study was aimed to investigate the therapeutic efficacy of HLH-2004 chemotherapy in patients with secondary hemophagocytic lymphohistiocytosis (sHLH). 10 cases of sHLH treated with HLH-2004 regimen at our department were analyzed retrospectively. The results showed that 7 patients had clinical response to HLH-2004 regimen, while other 3 patients had no clinical response. 5 cases did not complete initial therapy of 8 weeks. Out of 5 cases, 4 died in the process of chemotherapy, 1 patient abandoned for serious side effects but finally acquired remission following 4 cycles of CHOP regimen. 5 cases underwent the whole courses of initial therapy. Out of 5 cases, 3 patients acquired remission, and other 2 were not well controlled. Out of the 3 patients who had achieved remission, one died of relapse, and other 2 patients kept remission. Out of the 2 patients who were not well controlled, one patient died, but another patient acquired remission after being discharged. It is concluded that patients with infection-associated hemophagocytic syndrome (IAHS) have high rates of remission after receiving HLH-2004 regimen combining with effective antibiotics. However, patients with HLH secondary to EBV (EBV-HLH) or lymphoma (LAHS) have low rates of remission or are easy to get relapse after remission.

To observe the characteristics of vestibular-ocular reflex (VOR) of guinea pigs during eccentric sinusoidal rotation in different frequencies and radius, and compare them with that during axis rotation, obtain the parameters which reflect otolith functions, and provide experimental evidence for the establishment of otolith function test.Guinea pigs were placed in axis of rotation and in an heading out eccentric position apart from rotation axis of 330 mm, 660 mm and 990 mm respectively, their VOR were recorded and compared under stimulus of sinusoidal rotations in the frequencies of 0.1, 0.2, 0.3, 0.4, 0.5 and 0.6 Hz with the peak velocity of 60 degrees/s in each position.Both frequency and eccentric radius had significant effects on the VOR gain, it increased with the increase of frequencies and radius. The largest increase of the gain occurred at the frequencies of 0.3 and 0.4Hz, and no significant changes were observed above these frequencies.Enhancement ratio (ER) of VOR gain can reflect the extent of its increase with radius, and can be used as an index of otolith function, the stimulus profile of eccentric rotation at frequency of 0.4Hz and radius of 990mm is recommended as the stimulus profile for the otolith function test.

In order to evaluate the incidence of CCAAT/enhancer binding protein alpha (cebpa) gene mutation in patients with acute myeloid leukemia (AML), 22 AML patients with normal karyotype (NK-AML) were enrolled in this study, including de novo AML and relapsed AML. The cebpa gene was amplified by 2 stages using genomic DNA as template, the cebpa gene mutation amplified product was detected by direct sequencing or clone sequencing. The results showed that the cebpa mutations including deletion and insertion were found in 4 out of 22 AML patients (18.2%) and all of these 4 patients were M(2). Two patients had N-terminal nonsense mutation and the other two had C-terminal in-frame mutation. It is concluded that PCR combined with direct sequencing and clone sequencing can be used to detect cebpa mutations. cebpa mutations are mainly identified in M(2) subtype of NK-AML patients, its significance for prognosis needs to further investigate.

The human multidrug resistance gene (MDR1, ABCB1) codes for P-glycoprotein (P-gp) that affects the pharmacokinetics of many drugs. MDR1 single nucleotide polymorphisms (SNPs) are associated with drug clearance. Imatinib is a substrate of P-gp-mediated efflux. We investigated the MDR1 T1236C, G 2677T/A, and C3435T polymorphism in 52 patients with chronic myeloid leukemia treated with imatinib. The distribution of MDR1 1236, 2677, or 3435 genotypes was significantly different between the resistance patients and sensitivity patients. The resistance incidence correlated with the number of T alleles at locus 1236 and 3435. Resistance was higher for patients homozygous for the 1236T allele when compared to patients with CT/CC genotype groups (75% vs. 31.3%, P = 0.004). For the G2677T/A polymorphism, a better complete cytogenetic remission was observed for patients with genotype AG/AT/AA, when compared to other genotype groups (TT/GT/GG, P = 0.02). Patients with 3435 TT/CT genotypes showed a higher resistance when compared with patients with CC genotype (59.4% vs. 25%, P = 0.023). In conclusion, determination of 1236T, C3435T, and G2677T MDR1 polymorphisms might be useful in response prediction to therapy with imatinib in patients with CML.

The purpose of our study was to establish the profile of cortical reorganization in whole BPAI on rats and evaluate changes of cortical reorganization after repair of the median nerve with the contralateral C7 root transfer. Forty adult SD rats underwent whole roots avulsion of left brachial plexus, among them 20 received contralateral C7 root transfer to the injured median nerve. Intracortical microstimulation was performed in primary motor cortex (M1) at intervals of 3, 5, 7, and 10 months, postoperatively. The maps of motor cortical responses were constructed. Five normal rats were used as the control. Results showed that stimulating right M1 elicited motion of left vibrissae, submaxilla, neck, back, and left hindlimb after left BPAI, among them neck representation area replaced the forelimb area throughout the reorganization process. The left forelimb representation area was found in the left motor cortex 5 months after the contralateral C7 root transfer and existed in both motor cortexes at 7th postoperative month. The left forelimb representation area was detected only in right motor cortex at 10th month, postoperatively. In conclusions, after the contralateral C7 root transfer for repair of the median nerve in BPAI, the cortical reorganization occurred in a time-dependent reorganization. The findings from this study demonstrate that brain involves in the functional recovery after BPAI and repair with nerve transfer and suggest that efforts to improve the results from nerve repair should address the peripheral nerve as well as the brain.

This study was aimed to investigate the frequency of FMS-like tyrosine kinase 3 (FLT3) mutations including internal tandem duplication (ITD) mutation of juxtamembrane region and point mutation of the second tyrosine kinase domain (TKD) in acute myeloid leukemia (AML) patients and its clinical significance. The ITD mutation in FLT3 exon 14, 15 of bone marrow mononuclear cells was detected by genomic DNA-PCR, the TKD point mutation in FLT3 exon 20 was detected by genomic DNA-PCR combined with restriction endonuclease digest. The results indicated that among 131 newly diagnosed AML patients, 21 patients (16.0%) showed FLT3-ITD positive, 3 patients (2.3%) showed FLT3-TKD positive. None was found harboring both mutations. The WBC and bone marrow blast counts in FLT3-ITD positive patients seemed both higher than those in patients with wild-type FLT3 (FLT3-wt), but there was significant difference only in WBC count (p0.05). The complete remission (CR) rate in FLT3-ITD positive patients was 47.6%, which was significantly lower than that in FLT3-wt patients (88.1%, p0.05). There was no statistical difference in CR rate between FLT3-ITD positive and negative patients in 20 cases of M3; the CR rate in FLT3-ITD positive patients with non M(3) was 37.5 (6/16) which was obviously lower than that in FLT3-wt patients with non M3 (90.6%, 48/53) (p0.05). 3 FLT3-ITD positive patients with CR relapsed after CR for 14 (2-20) months with relapse rate 50% (3/6) which was higher than that in FLT3-wt patients (29.2%, 14/48). It is concluded that FLT3 mutation is common in AML patients, while FLT3-ITD mutation is more frequent than FLT3-TKD mutation. The AML patients with FLT3-ITD mutation have a poor prognosis, while FLT3-TKD point mutation does not significantly influences prognosis of the patients. Therefore early detection of FLT3 mutation may be important for targeting therapy and evaluating clinical prognosis of AML patients.

This study was aimed to explore the effect and adverse reaction of cyclosporine A (CsA) in treatment of pancytopenia without reticulocyte decrease but with elevated LDH. 10 patients were selected according to our standards and were treated by CsA. The curative effect and adverse reaction of patients were evaluated by following up for 6 - 116 months. The effect of CsA in the maintenance treatment of AA patient with an obvious rise of LDH was illustrated by means of typical case. The results indicated that 10 patients had different diagnosis, but had similar clinical and laboratory characteristics. Among them, 9 patients showed a relatively good curative reaction to CsA. Treatment of 1 patient was stopped because of pneumonia tuberculosis. It is concluded that the elevated LDH without reticuleocyte decrease may be a biomarker to predict the curative reaction to CsA for patients with pancytopenia. Selectively treating pancytopenia with CsA can obtain a higher curative reaction and maintenance treatment with CsA is an important factor for reducing recurrence of this disease.

This study was aimed to investigate the status of c-KIT, Fms-like tyrosine kinase 3 (FLT3) and Janus kinase 2 (JAK2) mutations in acute myeloid leukemia (AML) patients with t (8; 21) and to analyze their relation to clinical feature and prognosis. PCR, AS-PCR, restriction and sequencing methods were used respectively to detect the FLT3, JAK 2 and c-KIT mutations in 8 cases of de novo AML with t (8; 21) and 6 cases of relapsed AML with t (8; 21). The results showed that the c-KIT mutation was found in 2 cases out of 14 AML patients with t (8; 21) (14.3%), among them 1 case had c-KIT D816V mutation, the other had c-KIT D816Y mutation. The FLT3-ITD mutation was detect in 1 out of 14 patients (7.1%), but JAK2 mutation could not be detected in all 14 cases. In conclusion, tyrosine kinase mutation relates to AML with t (8; 21), patients with tyrosine kinase mutation may have higher relapse, extramedullary infiltration and poor prognosis. The screening c-KIT, FLT3 mutations may play an important role in evaluating prognosis and guiding treatment of t (8; 21) AML.

To investigate the efficacy and toxicity of standard-dose IA regimen (idarubicin and cytarabine) as induction therapy followed by FLAG regimen in patients with acute myeloid leukemia (AML), and its influence on peripheral stem cell mobilization.A total of 23 previously untreated de novo AML patients were enrolled. Thirteen patients were male, and 10 female, with ages ranging from 14 to 54 (median: 41) years. Cytogenetic analysis was performed for all patients. The IA regimen contained idarubicin (12 mg x m(-2) x d(-1), days 1 to 3) and cytarabine (100 mg x m(-2) x d(-1), days 1 to 7), and the FLAG regimen contained'fludarabine (50 mg/d, days 1 to 5), cytarabine (2 g x m(-2) x d(-1), days 1 to 5) and granulocyte colony-stimulating factor (G-CSF, 300 microg/d, days 0 to 5).After one course of induction therapy, the CR rate was 91.3%. The CR rate for patients with favourable and intermediate prognostic karyotypes was 100% and 91.3%, respectively. Nineteen patients in CR were consolidated with FLAG regimen, of which 6/9 (66.7%) patients were able to mobilize a sufficient number of CD34+ cells and successfully performed autologous stem cell transplantation. Four patients relapsed. The median survival duration was 19.5 months and median disease-free survival was 14 months. Myelosuppression and infections due to neutropenia were the most frequent adverse effects, severe nonhematologic toxicity and the early death were not observed in all patients.IA followed by FLAG regimen is effective and well tolerable in AML patients especially in those with favourable and intermediate prognostic karyotypes, and 1 to 2 courses of this therapy shows no influence on peripheral stem cell mobilization and subsequent autologous stem cell transplantation.

To evaluate the efficacy and toxicity of low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor (G-CSF) protocol for patients with relapsed acute myeloid leukemia (AML). A total of fifty relapsed patients have been enrolled, including 13 early relapsed and 37 late relapsed. 24 patients were male and 26 were female, with age ranging from 15 to 69 (median 47) years. Out of them, 7 patients relapsed after allogeneic peripheral blood stem cell transplantation (allo-PBSCT), 3 patients relapsed after autologous peripheral blood stem cell transplantation (auto-PBSCT), 25 patients relapsed after received regimens including high dose cytarabine and 15 patients relapsed after CR or stopping chemical therapy themself in course of consolidatory therapy. 30 relapsed patients received CAG regimen, and 20 patients (control group) received an anthracycline in combination with cytarabine. The results indicated that after one course, the complete remission (CR) rate was 46.7% (14/30), the CR rate after allo-PBSCT was 50% (3/6), the early death rate was 3.3% in CAG group; and CR rate was 30% (6/20) and the early death rate was 15% in control group. Myelosuppression was mild to moderate, and no severe nonhematologic toxicity was observed in two groups. The overall median times in CAG group and control group were 22 and 19 months respectively. In conclusion, CAG regimen as the induction therapy is effective and well tolerable with low side effects for relapsed patients who had received high dose cytarabine, auto-PBSCT or allo-PBSCT.

To investigate the frequency of derivative chromosome 9 [der (9)] deletions in patients with chronic myelogenous leukemia (CML), karyotype analysis in 138 patients with CML was performed with R-banding technique, and dual fusion fluorescence in situ hybridization (FISH) was used to detect der (9) deletion. The results showed that among 138 cases, 126 cases were Ph positive (91.3%) from which 122 cases were typical Ph translocation, 12 cases were Ph negative (8.7%). FISH detection revealed 23 with der (9) deletions out of 138 cases (16.7%), 20 out of 122 cases with typical Ph translocation showed typical Ph translocation (16.4%) and 3 out of 4 cases with variant Ph translocation had variant Ph translocation (75%). 20 cases were in chronic phase (CP) (17.2%), 3 cases were in blast crisis (BC) (17.6%), there was no significant difference in the frequency of the der (9) deletions between the cases in CP and in BC (p0.05). It is concluded that incidence of der (9) partial deletions in CML patients is 16.7%, FISH can effectively detect the der (9) deletions, and there is no correlation of der (9) deletion frequency between cases in different phases of CML.

The aim of this study was to evaluate the nucleophosmin (NPM1) gene exon 12 mutation in patients with acute myelogenous leukemia (AML) and its clinical characteristics. Genomic DNAs from 33 AML patients were amplified by PCR and sequencing for NPM1 mutations. The results showed that the NPM1 exon 12 mutations were found is 8 patients from 33 AML patients (24.2%) including 1 of M(1), 3 of M(2), 1 of M(4) and 3 of M(5). The NPM1 gene mutations were found in 7 out of 19 patients with normal karyotype and their incidence was significantly higher than that in patients with karyotype abnormalities (1/14, 7.1%, p0.005). The proportion of bone marrow blast cells and the count of peripheral white blood cells in patients with NPMI exon 12 mutation were higher than that in patients with wild type NPMI gene. It is concluded that the occurrence of NPM1 exon 12 mutations is observed more in AML patients with normal karyotype. NPM1 mutant cases are associated with more high amount of boon marrow blast cells and peripheral white blood cell count.

To evaluate the clinical significance of the application of fluorescence in situ hybridization (FISH) in detecting chronic myeloid leukemia (CML).Chromosome preparation was made by using 24-hour culture. FISH technique using dual color dual fusion (DC-DF) BCR/ABL probe was performed in all 158 cases and R-banding was also employed for karyotyping in some patients.Among the 158 cases, 98 cases were Ph positive, of which 69 cases (70.4%) were typical FISH pattern (1R1G2F), the other 29 cases (29.6%) showed 12 different types of atypical FISH pattern. The most frequent atypical patterns found were 1R1G1F in 7 cases (7.1%), 2R1G1F in 5 cases (5.1%), 1R1G2F and 1R1G3F in 4 cases (4.1%), 2R2G1F in 3 cases (3.1%). Karyotype analysis on 18 CML cases with atypical FISH patterns demonstrated that the atypical FISH patterns were due to variant translocation in 3 cases; the additional third signal was because of a supernumerary Ph chromosome. The karyotyping results did not conform to FISH results in four cases suggesting the conceivable mistakes in karyotyping. The 1R1G1F signal pattern seen in 3 cases with classical t(9;22) resulted from the deletion of derivative chromosome 9. The 1R1G2F signal pattern detected in 40% to 64% of interphase cells of 3 cases without Ph chromosome by conventional cytogenetic analysis suggested a submicroscopic translocation. Three cases treated with Glivec or bone marrow transplantation showed normal karyotypes with a small amount of BCR/ABL positive cells by FISH detection.FISH technique is of great value for the diagnosis of CML and confirmation of variant translocation, occult Ph translocation, derivative chromosome 9 deletion, therapeutic effect of interferon and Glivec as well as detection of minimal residual disease after bone marrow transplantation.

This study was aimed to investigate the characteristics of chromosome karyotype abnormality in patients with acute myeloid leukemia. 379 cases of de novo acute myeloid leukemia were enrolled in this study. Chromosome preparations were made on bone marrow cells by using direct method or short-term culture. Chromosome karyotypes were analyzed by R-banding technique. The results indicated that 216 out of 379 patients had clonal chromosome aberrations with the percentage of 56.99%, including 19 kinds of balanced translocations and 70 kinds of chromosome gain or loss. The most common structure and numerical abnormalities were t(15;17) and -Y with the percentage of 25.86% and 5.80%, respectively. -Y was accompanied by t(8;21) in 90.9% of the -Y abnormality cases, which accounted for 40.81% of t(8;21) positive cases. The abnormality of M(3) was significantly higher than the other FAB subtypes (p0.05). No significance was found between the male and female groups for the chromosome aberrations (p0.05). In conclusion, some specific chromosome aberrations are correlated with specific FAB subtype, which may contribute to the clinical diagnosis and subtyping of the disease.

This study was aimed to investigate the immunophenotypic characteristics of acute promyelocytic leukemia (APL). CD45/Side Scatter (SSC) gating strategy and multiparametric flow cytometry were used to determine immunophenotype of 143 patients with APL. The immunophenotypic features were compared between newly diagnosed APL patients and relapsed APL patients. 42 patients with HLA-DR(-) (non-APL AML, DR(-)AML) were randomly selected as controls. 31 out of 42 AML patients were CD34 negative, and their immunophenotypes were compared with those in newly diagnosed APL patients. The results showed that (1) CD34 and HLA-DR were both negative in 91.9% of newly diagnosed APL, while the positive rate of CD34 and HLA-DR elevated in relapsed cases (3.0% vs 37.5%, 3.9% vs 37.5%). The positive rate of CD34 in HLA-DR(-) AML group was higher than that in newly diagnosed APL group (23.4% vs 3.0%). The positive level of CD34 in newly diagnosed APL group was lower than that in HLA-DR(-) AML group; (2) the positive rate of CD33 in newly diagnosed APL group was higher than that in other groups (97.0% vs 75.0%, 83.3%, 83.9%), as well as the the positive level of CD33 (p0.05). (3) no lymphoid antigen other than CD2 was expressed in newly diagnosed APL group. The positive rate of CD7 was 9.5% in DR(-) AML group and 6.5% in CD34(-)/DR(-) AML group, both were higher than those of newly diagnosed APL group (p0.05). It is concluded that the immunophenotyping can provide proof to the rapid diagnosis of APL. For those patients with DR(-) AML, it may be helpful to identify APL depending on following features: low or negative CD34 expression, homogeneous and bright expression of CD33, no lymphoid antigens other than CD2, higher SSC.

In order to evaluate the cytogenetic features and clinical significance of chronic myeloid leukemia (CML), chromosome preparation of bone marrow cells was made by using 24-hour culture, and R-banding technique was employed for karyotyping in 362 patients with CML. The patients were divided into two groups of chronic phase (CP) and blast crisis (BC). The results showed that the incidence of additional chromosome, variant translocation and Philadelphia (Ph) negative, bcr/abl positive CML with abnormal chromosomes in CP group were 70 cases (26.1%), 19 cases (7.1%), 4 cases (1.5%), and were 50 cases (53.2%), 8 cases (8.5%), 4 cases (4.3%) in BC group. Among the 362 cases, 324 cases (89.5%) were Ph positive. Classic translocation was found in 297 cases (91.7%) and variant translocation in 27 cases (8.3%), including 13 cases of simple variant, 13 cases of complex variant and 1 case of marked Ph. Special karyotypes were found in 120 out of 362 cases. Analysis of these karyotypes demonstrated that the most common numerical abnormalities were +Ph (21.7%), +8 (10.0%), +21 (10.0%), +19 (7.5%) and structure abnormalities were i(17q) (13.3%). In conclusion, compared to chronic phase, the incidence of additional chromosome, variant translocation and so on are much higher at in blast crisis. It is feasible to evaluate the progress of the disease by karyotype analysis.

Chronic myeloid leukemia (CML) is characterized by the formation of the BCR/ABL fusion gene, as a consequence of the Philadelphia (Ph) translocation between chromosomes 9 and 22. This study was to investigate the incidence and prognostic significance of derivative chromosome 9 (der(9)) deletions in CML patients who received hydroxyurea treatment in the chronic phase.Fluorescence in situ hybridization (FISH) analysis was used to assess the der(9) deletion status of 48 CML patients in blast crisis (CMLBC).Among the 48 CML patients, 8 (16.7%) showed der(9) deletions, and the deletions were also existent at diagnosis. The median duration of the chronic phase for patients with der(9) deletions was 18 (range 4-38) months compared to 48 (range 0-204) months for patients without deletions (p0.001). Der(9) deletions were not associated with increased karyotypic instability. There was no difference in the probability of the der(9) deletions between the cases having progressed to myeloid or lymphoid blast crisis.The results indicated that the FISH technique could effectively detect der(9) deletions. CML patients with der(9) deletions show more rapid progression and poorer prognosis, and the deletion status is a powerful prognostic factor.

The aim of this study was to explore the clinical effect and complications of allogeneic peripheral blood stem cell transplantation (allo-PBSCT) in hematologic malignancies through retrospective analysis of 75 patients (42 male, 33 female; aged from 13 to 72 years old) received allo-PBSCT from HLA matched (n=61) or haploidentical donors (n=14). 75 patients included 35 patients with chronic myeloid leukemia (CML), 30 patients with acute myeloid leukemia, 5 patients with severe aplastic anemia, 3 patients with acute lymphocytic leukemia, one patients with multiple myeloma and one patients with paroxysmal nocturnal hemoglobinuria. Conditioning regimens were (1) Cy/TBI or Bu/Cy; (2) Cy/TBI+Ara-C; (3) fludarabine+TBI/or (CTX+ATG). Minimal residual disease has been monitored regularly by PCR and FISH. Patients received cyclosporine A and methotrexate or ATG and anti-CD25 monoclonal antibody and mycophenolate mofetil for graft-versus-host disease (GVHD) prophylaxis. Relapsing patients after transplantation received DLI and/or chemotherapy. Patient with CML were treated with imatinib. The results showed that 74 patients had hematopoietic reconstitution, and eventually converted to full donor chimerism by FISH or PCR-STR. The median time for the initial hematopoietic reconstitution was 15 (5-25) days. 46 out of 75 patients were alive and median duration was 23 (2-61) months. Among 29 dead patients, 9 died of disease relapse, 7 died of III-IV grade of acute GVHD and 7 died of severe infection (2 patients developed interstitial pneumonia). 9 out of 14 patients received haploidentical transplantation were alive, and the time of event-free survival was 30 (6-53) months, the mean survival time of 5 died patients was 7 (2-17) months. 16 patients were infected by cytomegalovirus, 2 of them died of interstitial pneumonia. None of them suffered from veno-occlusive disease in the liver. It is concluded that allo-PBSCT is effective to treat refractory hematologic diseases, and DLI/or chemotherapy should be used in the patients relapsing after transplantation.

In order to investigate the frequency of MPLW515L and JAK2V617F point mutations of the patients with myeloproliferative disease (MPD) in Nanjing area, MPLW515L and JAK2V617F point mutations were simultaneously detected by alleles specific polymerase chain reaction (AS-PCR) and sequencing in 190 MPD patients. The results showed that MPLW515L point mutation was detected in 1 out of 102 essential thrombocythemia (ET) patients (1.0%) and was not detected in 32 polycythemia vera (PV) patients, 13 idiopathic myelofibrosis (IMF) patients, 43 chronic myelogenous leukemia (CML) patients. JAK2V617F point mutation was detected in 20 out of 32 PV patients (62.5%), 43 out of 102 ET patients (42.2%), 5 out of 13 IMF patients (38.5%), and was not detected in 43 CML patients. It is concluded that MPLW515L point mutation exists in ET patient, but is not found in PV, IMF and CML. JAK2V617F point mutation exists in PV, ET and IMF, but not in CML.

Chronic myeloid leukemia (CML) progression is characterized by occurrence of new cytogenetic and molecular abnormalities. In the previous study, we have shown the important role of GATA-2 L359 V mutation in CML progression. To further ascertain the truth of transcription factor GATA-2 in hematological malignancies, we expanded our study to GATA-2 full length by directly sequencing and applied MassARRAY assay into GATA-2 L359 V mutation analysis. Finally, no GATA-2 L359 V mutation was found in 270 acute myeloid leukemia, 30 myelodysplastic syndrome, 50 acute lymphoblastic leukemia, 12 chronic lymphocytic leukemia, 40 CML chronic phase and 286 BCR/ABL negative myeloproliferative disorders except CML blast crisis. A new variation of GATA-2 resulted in P250A change was identified, which was not found to have statistical difference between patients with hematological malignancies and healthy control. Hence, we concluded GATA-2 L359 V is exclusively associated with CML progression but not other hematological malignancies and P250A is a new single nucleotide polymorphism.

To evaluate the frequency of jak2v617f mutation and analyze its correlation with clinical features of primary thrombocythemia (PT) patients, the mutation was detected by allele specific polymerase chain reaction (AS-PCR), the clinical and laboratory data in 66 PT patients with and without jak2v617f mutation were compared and clinical features of these PT patients were retrospectively analyzed. The results showed that among 66 patients, 27 patients (41%) had the mutation. The patients carrying the mutation displayed higher bone marrow erythropoiesis (26.9%+/-9.4% vs 16.3%+/-8.7%, p0.05), higher ratio of granulopoiesis/erythropoiesis (2.9+/-1.8 vs 5.2+/-2.9, p0.05) and higher incidence of microvascular disturbances (29.6% vs 5.1%, p0.05). However, the age, gender, leukocyte and platelet counts, hemoglobin level, bone granulopoiesis, splenomegaly, history of thrombosis and hemorrhage had no difference between patients with and without the mutation. It is concluded that the frequency of jak2v617f mutation in primary thrombocythemia patients is 41%. The presence of the jak2v617f mutation is associated with a higher bone marrow erythropoiesis in primary thrombocythemia patients at diagnosis.

To evaluate the prognostic value of lactate dehydrogenase (LDH) and beta2-microglobulin (beta2-MG) in chronic lymphocytic leukemia (CLL), a total of 141 cases of CLL had been investigated retrospectively. The Kaplan-Meier method was used to estimate the overall and failure-free survival distributions. Cox regression was used in univariate and multivariate analysis of potential predictors for overall survival. In multivariate analysis, the expression levels of LDH and beta2-MG were divided into 3 groups: (1) elevation of both LDH and beta2-MG levels; (2) elevation of LDH or beta2-MG levels alone; (3) normal levels of both LDH and beta2-MG. The results showed that serum LDH and beta2-MG levels of patients in Binet C were significantly higher than those in Binet A (p=0.034 and p=0.035). The level of serum beta2-MG was not correlated with lymphocyte count (p=0.756). Binet C and high LDH level were associated with significantly shorter overall survival. beta2-MG was not proved to have any association with overall survival. The overall survival time in group of elevation of both LDH and beta2-MG levels was shorter than that in group of normal levels of both LDH and beta2-MG. It is concluded that serum LDH level and Binet stage are important prognostic factors for CLL.

To explore the value of multiplex fluorescence in situ hybridization (M-FISH) in combination with whole chromosome painting (WCP) in the detection of complex chromosomal aberrations (CCAs) in myelodysplastic syndromes (MDS).M-FISH was used in seven MDS patients with R-banding CCAs to refine the complex chromosomal rearrangements, and to identify cryptic translocations and characterization of marker chromosomes. Dual-color WCP procedures were further performed in 7 cases to confirm some rearrangements detected by M-FISH.M-FISH confirmed all results of R-banding. The composition and origin of 6 kinds of marker chromosomes, 9 kinds of chromosomes with additional material undetermined and 5 kinds of derivative chromosomes undefined by conventional cytogenetics (CC) were defined after M-FISH analysis; four kinds of cryptic translocations overlooked by CC were found on derivative chromosomes and previously normal appearing chromosomes. In addition, M-FISH revealed some nonrandom aberrations: aberrations involving chromosome 17 and -5/5q- were the two most frequent aberrations. Some misclassified and missed chromosomal aberrations by M-FISH were corrected by WCP.M-FISH is a powerful molecular cytogenetic tool in clarification of CCAs. Complementary WCP helps us to identify misclassified and missed chromosomal aberrations by M-FISH. CC in combination with molecular cytogenetic techniques, such as M-FISH and WCP, can unravel complex chromosomal aberrations more precisely.