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The study aims to understand geneome diversification and complexity that developed in Acute myeloid leukemia (AML). Next-generation sequencing (NGS) was used to identify the genetic profiles of 22 genes relevant to hematological malignancy in 204 patients with de novo non-M3 AML. At time of initial diagnosis, at least one mutation was identified in 80.9% of patients (165/204). The most commonly mutated gene was NPM1 (22.1%), followed by ASXL1 (18.1%), TET2 (18.1%), IDH2 (15.7%), CEBPA (14.7%), FLT3-ITD (13.2%) and DNMT3A (11.8%). Mutations landscape analysis indicated several patterns of co-occurring and mutual exclusive gene mutations. Some correlation was observed between gene mutations and clinicohematological features. Multivariate analysis showed that age >60 years, karyotypes, IDH2 and KIT mutations were the independent unfavorable prognostic factors for OS; NPM1-mut/ FLT3-ITD-wt was independently correlated with prolonged OS; whereas the independent poor risk factors for RFS were karyotypes, high WBC and RUNX1 mutation. According to different genotype demonstrated by multivariate analysis, 163 patients with intermediate-risk cytogenetics were classified into three subgroups: patients with NPM1-mut/ FLT3-ITD-wt or biallelic CEBPA mutation as favorable risk, patients with KIT, IDH2, TP53 or NRAS mutations as unfavorable risk, and the remaining was the intermediate risk. We also obtain information of clonal evolution during leukemia progression by observing five patients who underwent repeat NGS at relapse in our cohort. NGS techniques is a useful tool for discovering related gene mutations and clonal evolution in AML genomes, leading to novel targeted therapeutic approaches that could improve patients outcomes. [ABSTRACT FROM AUTHOR]

Molecular abnormalities are frequent in core-binding factor (CBF) AMLs, but their prognostic relevance is controversial. Sixty-two patients were retrospectively analyzed and 47 harbored at least one gene mutation with a next-generation-sequencing assay. The most common molecular mutation was KIT mutation (30.6%), followed by NRAS (24.2%) and ASXL1 (14.5%) mutations, which was associated with a higher number of bone marrow blasts (p =.049) and older age (p =.027). The survival analysis showed KIT mutation adversely affected the overall survival (OS) (p =.046). NRAS mutation was associated with inferior OS (p =.016) and RFS (p =.039). Eight patients carried co-mutations of KIT and NRAS and had worse OS (p =.012) and RFS (p =.034). The multivariate analysis showed age ≥60 years and additional chromosomal abnormalities were significant adverse factors for OS. Thus, co-mutations of KIT and NRAS were significantly associated with a poor prognosis and should be taken into account when assessing for prognostic stratification in patients with CBF-AML. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 22-year-old Chinese male patient who was brought to the hospital because of recurrent fever, and anemia for 3 months. The patient found to have acute promyelocytic leukemia (APL) associated with a novel STAT5B-RARA fusion gene transcript. The authors also discuss the important role played by Src homology 2 (SH2) in signal transduction via tyrosine protein kinase.

The usefulness of flow cytometric variable β-chain repertoire (FC-Vβ) and T-cell receptor gene rearrangement (TCR-GR) analyses for differentiating T-cell large granular lymphocytic leukemia (T-LGLL) from reactive T-large granular lymphocyte (T-LGL) lymphocytosis has been insufficiently studied to date. In this study, we analyzed the diagnostic value of TCR-GR and FC-Vβ analysis in T-LGLL, and compared these results. In our study, FC-Vβ analysis was positive in all cases of T-LGLL, and clonality assessment of FC-Vβ had equal sensitivity and specificity to GeneScanning analysis but was more sensitive than heteroduplex analysis. Suspected T-cell clonality can best be addressed by evaluating two TCR targets (TCRβ and TCRγ), either in parallel or consecutively. Signal transducer and activator of transcription 3 (STAT3) mutation may provide a diagnostic tool for classifying some cases of T-LGL lymphocytosis as true T-LGLL. Our results further demonstrate a significant correlation of STAT3 mutation with pure red cell aplasia, neutropenia, hepatomegaly, β2-microglobulin and anemia. [ABSTRACT FROM AUTHOR]

Poly(γ-benzyl L-glutamate)/poly(ethylene glycol) (PBLG/PEG) polymer blend membranes were prepared by casting the polymer blend solution in chloroform. Surface morphologies of the polymer blend membranes were investigated by atomic force microscopy (AFM) and scanning electron microscopy (SEM). Thermal and mechanical properties of the polymer blend membranes were researched using differential scanning calorimeter (DSC) and tensile tests. It was revealed that the introduction of PEG could exert outstanding effects on the morphology and the properties of the polymer blend membranes. [ABSTRACT FROM AUTHOR]

NPM1 mutation is the most common molecular abnormality in patients with acute myeloid leukemia (AML), especially normal karyotype AML (NK-AML), and is associated with a favorable prognosis in the absence of concomitant FLT3-ITD. Like other molecular abnormalities such as FLT3-ITD, C/EBPα and c-Kit mutation, NPM1 mutation normally presents as a recurrent molecular abnormality. The NPM1 mutation is generally used as a molecular marker in the prognosis evaluation of a patient with AML. Here, we report a different case. He was first diagnosed with NPM1 mutation-positive acute monocytic leukemia. However, he achieved no remission, but the NPM1 mutation dramatically became negative after induction chemotherapy. Finally, he achieved complete remission after salvage chemotherapy and the NPM1 mutation was still negative. To our knowledge, this is a rare case according to the worldwide published literature. [ABSTRACT FROM AUTHOR]

A series of poly(vinyl alcohol) (PVA)/polyurethane (PU) blend membranes were prepared by casting the polymer blend solution in dimethyl sulfoxide (DMSO). Structure and morphologies of PVA/PU blend membranes were investigated by atomic force microscopy (AFM) and scanning electron microscopy (SEM). Thermal, mechanical, and chemical properties of PVA/PU blend membrane were studied by differential scanning calorimetry (DSC), tensile tests, and surface contact angle tests. It was found that the introduction of PU could exert marked effects on the morphology and the properties of PVA membrane. [ABSTRACT FROM PUBLISHER]

The human multidrug resistance (MDR1, ABCB1) gene encodes P-glycoprotein (P-gp), which affects the pharmacokinetics of many drugs. Here, we investigated whether common MDR1 single nucleotide polymorphisms (SNPs) (C1236T, C3435T, and G2677T/A) affect predisposition to chronic lymphocytic leukemia (CLL). Genotyping was performed in 150 patients with CLL and 117 controls using polymerase chain reaction (PCR)-based assays. Haplotypes were inferred using the PHASE algorithm. We found comparable allele and genotype frequencies among patients with CLL and controls. Moreover, patient and control groups did not differ regarding MDR1 haplotype distribution ( p == 0.97). Furthermore, no correlation was shown between the MDR1 1236, 3435, or 2677 genotypes and Binet stage, unmutated immunoglobulin heavy-chain variable region (IGHV) status, CD38 expression, ZAP-70 expression, and p53 deletion. In conclusion, our results do not support a major influence of MDR1 variants on the risk of CLL, and these genomic polymorphisms are not associated with clinical prognostic factors in Chinese patients with CLL. [ABSTRACT FROM AUTHOR]

Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia in the Western countries, however, it is infrequent in the Eastern countries. The direct antiglobulin test (DAT) may be positive at some time during the disease course of CLL. The aim of this study was to explore the prognostic impact of positive DAT at diagnosis in Chinese patients with CLL. In 123 Chinese patients with CLL, 34 (27.6%) patients presented with a positive DAT at diagnosis. However only 12 patients (9.8%) with a positive DAT developed autoimmune hemolytic anemia (AHA). According to the correlation analysis, advanced Binet stage (p < 0.001), high level of serum lactate dehydrogenase (LDH) (p = 0.003) and β2-microglobulin (β2-M) (p = 0.011), unmutated immunoglobulin heavy chain variable gene status (p < 0.001), positive ZAP-70 (p = 0.012), and trisomy 12 cytogenetic aberration (p = 0.004) emerged as factors significantly related to the occurrence of DAT-positive. Patients with positive DAT had significantly shorter survival times than patients with negative DAT (p = 0.009). Five-year OS percentages of DAT-positivity and DAT-negative patients were 72.8% and 97.5%, respectively. It was showed that DAT status might be applied for the assessment of prognosis in patients with CLL. [ABSTRACT FROM AUTHOR]

As JAK2 V617F, MPL W515L is a novel acquired mutation that induces constitutive cytokine-independent activation of the JAK-STAT pathway in myeloproliferative disorders (MPD). The discovery of this mutation provides a novel mechanism for activation of signal transduction in hematopoietic malignancies. To investigate its prevalence in Chinese patients with MPD, we introduced allele-specific PCR (AS-PCR) combined with sequence analysis to simultaneously screen MPL W515L and JAK2 V617F mutations in 190 MPD patients. MPL W515L mutation was found to be harbored in only one of 102 patients, who had essential thrombocythemia (ET, 1.0%) and was not detected in patients with polycythemia vera (PV), idiopathic myelofibrosis (IMF), and chronic myelogenous leukemia (CML). Sixty-eight BCR/ABL-negative MPD patients (46.3%) were found harboring JAK2 V617F mutation (PV, 62.5%; ET, 42.1%; IMF 38.1%). Furthermore, MPL W515L and JAK2 V617F mutations were not detected in patients of acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndromes, and CML. It has been shown that MPL W515L mutations may contribute to the primary molecular pathogenesis of Chinese patients with ET. [ABSTRACT FROM AUTHOR]