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Background Acute myeloid leukemia (AML) is a challenging heterogenous hematologic malignancy characterized by suboptimal outcomes. Genetic characterization of AML enhanced the understanding of individualized patient’s risk and led to the development of new therapeutic strategies. Gene expression analysis facilitates detection of new diagnostic, prognostic, and predictive biomarkers. This necessitates the expansion of diagnostic testing with higher throughput technologies, such as targeted next-generation sequencing (NGS).Objectives To study the expression profiles of MECOM and BAALC genes in a cohort of newly diagnosed Egyptian AML patients via Oncomine Myeloid Research assay (OMA) by NGS technology in addition to studying their potential prognostic role and impact on overall survival (OS).Methods The OMA was used to evaluate the expression levels of MECOM and BAALC genes and five control genes (FBXW2, PUM1, TRIM27, PSMB2, and EIF2B1), in twenty-four newly diagnosed AML patients by NGS technology, using RNA extracted from bone marrow aspirate (BMA) specimens.Results Gene expression analysis of MECOM and BAALC genes revealed that MECOM overexpression was significantly associated with the presence of lymphadenopathy and the high MECOM median expression level was significantly associated with lower hemoglobin concentrations at presentation. BAALC overexpression showed significant associations with the presence of CD34, the presence of wild type NPM1 mutation, and the absence of FLT3-ITD mutations. However, BAALC underexpression was significantly associated with normal cytogenetics, while its overexpression was associated with adverse and favorable cytogenetics, with a statistically significant difference between them (p = 0.049)*. Statistically significant positive correlation was found between BAALC expression levels and postinduction BM blast percentages. Among these two genes, only high BAALC expression had significantly shorter OS in AML patients based on the log rank test (p = 0.037)*.Conclusion BAALC expression might be a specific molecular marker used for the assessment of prognosis and OS in AML patients and might be used in the future as targeted therapy in AML, aiming to improve patient outcomes and OS.

Purpose: Acute myeloid leukemia (AML) is the most prevalent acute leukemia in adults. It possesses different cytogenetic and molecular features. The expression of Wilms tumor-1 (WT1), brain and acute leukemia, cytoplasmic (BAALC) and ETS-related gene (ERG) might be considered as prognostic factors in AML patients. The aim of this study was to determine the mRNA expressions of WT-1, BAALC and ERG genes in bone marrow of mononuclear cells and their effects on complete remission in the Iranian AML patients, pre- and post- chemotherapy. Methods: Forty AML patients with normal karyotype were evaluated. The mRNA gene expressions were measured with quantitative real-time PCR in bone marrow of mononuclear cells of AML patients at the baseline and after chemotherapy. The subtypes of AML and flow cytometry panel were also assessed. Complete remission (CR) after the treatment was addressed for all patients. Results: The mRNA expressions of WT-1, BAALC and ERG were significantly decreased after the treatment (p= 0.001, 0.017, 0.036). WT-1 mRNA expression was inversely correlated with CR after chemotherapy (P =0.024). There was also significant correlation between baseline expression of BAALC and CR (P=0.046). No significant correlation was observed between ERG and CR pre- and post- chemotherapy (P =0.464 and 0.781). There was also significant correlation between BAALC mRNA expression and CD34+ (P

This meta-analysis examined the prognostic role of brain and acute leukemia, cytoplasmic (BAALC), Ecotropic virus integration site-1 (EVI1) and Wilms' tumor 1 (WT1) genes at different time-points during conventional chemotherapy. A systematic search of publications indexed in the electronic databases from January 1988 to October 2020 was performed. Over 7525 cases of AML from 25 studies were involved. At diagnosis, overexpression of either BAALC or EVI1 had a negative impact on complete remission achievement (Summary Odds ratios [SORs] for BAALC = 0.32; SORs for EVI1 = 0.49) and survival outcome. The summary hazard ratios of overall survival (OS) and disease-free survival (DFS) were 1.97 and 2.04 for BAALC and 1.33 and 1.86 for EVI1, respectively. The prognostic value of pretreatment WT1 levels was heterogeneous while subgroup analyses unveiled that overexpressed WT1 may correlate with a favorable outcome (summary hazard ratio [SHR] for OS = 0.42). Both WT1 and BAALC played a role in prognosis assessment at post-induction and the diagnostic performance of WT1 transcript reduction was superior to the absolute WT1 level. Post-consolidation WT1 overexpression consistently indicated an increased risk of relapse, while the combined HR for RFS was statistically insignificant (SHR = 4.22). These findings confirm the application of BAALC and EVI1 at diagnosis, WT1 after induction chemotherapy in AML patients throughout conventional chemotherapy. [ABSTRACT FROM AUTHOR]

Introduction: Acute myeloid leukemia with normal cytogenetics (CN-AML) represents a heterogeneous group having diverse genetic mutations. Understanding the significance of each of these mutations is necessary. In this study, we evaluated the prognostic role of MN1 expression in adult CN-AML patients., Method: One hundred and sixty-three de-novo adult AML patients were evaluated for MN1 expression by real-time PCR. MN1 expression was correlated with the clinical characteristics of the patients and their outcomes., Results: Higher MN1 expression was associated with NPM1 wild-type (p<0.0001), CD34 positivity (p=0.006), and lower clinical remission rate (p=0.027). FLT3-ITD and CEBPA mutations had no association with MN1 expression. On survival analysis, a high MN1 expression was associated with poor event-free survival (Hazard Ratio 2.47, 95% Confidence Interval: 1.42-4.3; p<0.0001) and overall survival (Hazard Ratio 4.18, 95% Confidence Interval: 2.17-8.08; p<0.0001). On multivariate analysis, the MN1 copy number emerged as an independent predictor of EFS (p<0.0001) and OS (p<0.0001)., Conclusion: MN1 expression is an independent predictor of outcome in CN-AML.

Brain and Acute Leukemia, Cytoplasmic (BAALC) is a protein that controls leukemia cell proliferation, differentiation, and survival and is overexpressed in several cancer types. The gene is located in the chromosomal region 8q22.3, an area commonly amplified in breast cancer and associated with poor prognosis. However, the expression and potential role of BAALC in breast cancer has not widely been examined. This study investigates BAALC expression in human breast cancers with the aim of determining if it plays a role in the pathogenesis of the disease. BAALC protein expression was examined by immunohistochemistry in breast cancer, and matched lymph node and normal breast tissue samples. The effect of gene expression on overall survival (OS), disease-free and distant metastasis free survival (DMFS) was assessed in silico using the Kaplan-Meier Plotter (n=3,935), the TCGA invasive breast carcinoma (n=960) and GOBO (n=821) data sets. Functional effects of BAALC expression on breast cancer proliferation, migration and invasion were determined in vitro. We demonstrate herein that BAALC expression is progressively increased in primary and breast cancer metastases when compared to normal breast tissue. Increased BAALC mRNA is associated with a reduction in DMFS and disease-free survival, but not OS, in breast cancer patients, even when corrected for tumor grade. We show that overexpression of BAALC in MCF-7 breast cancer cells increases the proliferation, anchorage-independent growth, invasion, and migration capacity of these cells. Conversely, siRNA knockdown of BAALC expression in Hs578T breast cancer cells decreases proliferation, invasion and migration. We identify that this BAALC associated migration and invasion is mediated by focal adhesion kinase (FAK)-dependent signaling and is accompanied by an increase in matrix metalloproteinase (MMP)-9 but not MMP-2 activity in vitro. Our data demonstrate a novel function for BAALC in the control of breast cancer metastasis, offering a potential target for the generation of anti-cancer drugs to prevent breast cancer metastasis.

Brain and Acute Leukemia, Cytoplasmic (BAALC) is a protein that controls leukemia cell proliferation, differentiation, and survival and is overexpressed in several cancer types. The gene is located in the chromosomal region 8q22.3, an area commonly amplified in breast cancer and associated with poor prognosis. However, the expression and potential role of BAALC in breast cancer has not widely been examined. This study investigates BAALC expression in human breast cancers with the aim of determining if it plays a role in the pathogenesis of the disease. BAALC protein expression was examined by immunohistochemistry in breast cancer, and matched lymph node and normal breast tissue samples. The effect of gene expression on overall survival (OS), disease-free and distant metastasis free survival (DMFS) was assessed in silico using the Kaplan-Meier Plotter (n=3,935), the TCGA invasive breast carcinoma (n=960) and GOBO (n=821) data sets. Functional effects of BAALC expression on breast cancer proliferation, migration and invasion were determined in vitro. We demonstrate herein that BAALC expression is progressively increased in primary and breast cancer metastases when compared to normal breast tissue. Increased BAALC mRNA is associated with a reduction in DMFS and disease-free survival, but not OS, in breast cancer patients, even when corrected for tumor grade. We show that overexpression of BAALC in MCF-7 breast cancer cells increases the proliferation, anchorage-independent growth, invasion, and migration capacity of these cells. Conversely, siRNA knockdown of BAALC expression in Hs578T breast cancer cells decreases proliferation, invasion and migration. We identify that this BAALC associated migration and invasion is mediated by focal adhesion kinase (FAK)-dependent signaling and is accompanied by an increase in matrix metalloproteinase (MMP)-9 but not MMP-2 activity in vitro. Our data demonstrate a novel function for BAALC in the control of breast cancer metastasis, offering a potential target for the generation of anti-cancer drugs to prevent breast cancer metastasis. [ABSTRACT FROM AUTHOR]

Purpose: Acute myeloid leukemia (AML) is the most prevalent acute leukemia in adults. It possesses different cytogenetic and molecular features. The expression of Wilms tumor-1 (WT1), brain and acute leukemia, cytoplasmic (BAALC) and ETS-related gene (ERG) might be considered as prognostic factors in AML patients. The aim of this study was to determine the mRNA expressions of WT-1, BAALC and ERG genes in bone marrow of mononuclear cells and their effects on complete remission in the Iranian AML patients, pre- and post- chemotherapy. Methods: Forty AML patients with normal karyotype were evaluated. The mRNA gene expressions were measured with quantitative real-time PCR in bone marrow of mononuclear cells of AML patients at the baseline and after chemotherapy. The subtypes of AML and flow cytometry panel were also assessed. Complete remission (CR) after the treatment was addressed for all patients. Results: The mRNA expressions of WT-1, BAALC and ERG were significantly decreased after the treatment (p= 0.001, 0.017, 0.036). WT-1 mRNA expression was inversely correlated with CR after chemotherapy (P =0.024). There was also significant correlation between baseline expression of BAALC and CR (P=0.046). No significant correlation was observed between ERG and CR pre- and post- chemotherapy (P =0.464 and 0.781). There was also significant correlation between BAALC mRNA expression and CD34+ (P <0.001). Conclusion: The present study showed that WT-1 decreased significantly after standard chemotherapy which could have favorable effects on CR. Also, the high expression of BAALC could have a poor prognostic role in AML patients. The identification of these gene expressions can be an efficient approach in targeted therapy among AML patients. [ABSTRACT FROM AUTHOR]

The high expression of brain and acute leukemia, cytoplasmic (BAALC) and ETS‐related gene (ERG) has been reported to influence the outcome in acute myeloid leukemia (AML), but due to limited prospective studies, their role as prognostic factors is unclear. At diagnosis, the prognostic value of BAALC and ERG expression with respect to other cytogenetic and molecular markers was analyzed in 149 AML patients. Patients were divided into quartiles which resulted in the formation of four groups (G1–G4) based on expression values of BAALC and ERG and clinical response defined across groups. Groups with similar survival probabilities were merged together and categorized subsequently as high versus low expressers. Patients with high BAALC and ERG expression had significantly lower overall survival (OS; BAALC: p = 0.001 at 5 years 29.4% vs. 69.8%; ERG: p < 0.0001 at 5 years 4% vs. 50.4%) and disease‐free survival (BAALC: p = 0.001 at 5 years 19.5% vs. 69.8%; ERG: p < 0.0001 at 5 years 4.2% vs. 47%). Patients were further stratified combining BAALC and ERG expression in an integrative prognostic risk score (IPRS). After a median follow‐up of 54 months (95% CI 45–63 months) among survivors, IPRS for high versus low expressers was a significant predictor for OS (BAALC + ERG: 4% vs. 71.6%, p < 0.0001) and DFS (BAALC + ERG: 4.5% vs. 74.1%, p < 0.0001). In a multivariate model, IPRS of BAALC + ERG expression retained prognostic significance for OS (hazard ratio [HR] 2.96, 95%CI 1.91–4.59, p < 0.001) and DFS (HR 3.61, 95%CI 2.26–5.76, p < 0.001). [ABSTRACT FROM AUTHOR]

For most acute myeloid leukemia (AML) patients, an allogeneic hematopoietic stem cell transplantation (HSCT) offers the highest chance of sustained remissions and long-term survival. At diagnosis, high expression of the AML-associated genes BAALC (brain and acute leukemia, cytoplasmic) and MN1 (meningioma-1) were repeatedly linked to inferior outcomes in patients consolidated with chemotherapy while data for patients receiving HSCT remain limited. Using clinically applicable digital droplet PCR assays, we analyzed the diagnostic BAALC/ABL1 and MN1/ABL1 copy numbers in 302 AML patients. High BAALC/ABL1 and MN1/ABL1 copy numbers associated with common adverse prognostic factors at diagnosis. However, while high diagnostic copy numbers of both genes associated with shorter event free survival (EFS) and overall survival (OS) in patients receiving chemotherapy, there was no prognostic impact in patients undergoing HSCT. Our data suggests that the adverse prognostic impact of high BAALC and MN1 expression are mitigated by allogeneic HSCT. But preHSCT BAALC/ABL1 and MN1/ABL1 assessed in remission prior to HSCT remained prognosticators for EFS and OS independent of the diagnostic expression status. Whether allogeneic HSCT may improve survival for AML patients with high diagnostic BAALC or MN1 expression should be investigated prospectively and may improve informed decisions towards individualized consolidation options in AML. [ABSTRACT FROM AUTHOR]

The aim of this work is to investigate the different expression patterns of B cell-specifics moloney murine Leukemia virus integration site-1 (BMI-1) and brain and acute leukemia, cytoplasmic (BAALC) genes, their prognostic and clinical significance in newly diagnosed cytogenetically heterogenous adult acute myeloid leukemia patients. BMI-1 and BAALC expression was detected in the bone marrow of patients using quantitative real-time reverse transcription polymerase chain reaction with cut off value set at 50th percentile for both genes. BMI-1 and BAALC overexpression was detected in 50% of cases which suggest their potential as molecular markers. A statistical significant correlation was found between BMI-1 expression with hepatomegaly (P value = 0.007), hemoglobin level-grouped (P value = 0.047) and cytogenetic risk groups (P value = 0.036). There was a statistically significant correlation between BAALC and age (P value = 0.015), lymphadenopathy (P value = 0.043), CD34 expression (P value = 0.003) and near statistical significance with FAB sub-groups (P value = 0.054). No statistical significance was noted for other hematological findings and response to treatment except for BAALC gene and treatment response (P value = 0.014). No statistical significance in overall survival and disease free survival for both genes was found. Their prospective screening in combination with other molecular markers can help refine myeloid leukemia staging and prognosis toward optimizing therapeutic interventions. [ABSTRACT FROM AUTHOR]

Objective: To investigate the expressions and clinical significances of ERG, MDR1 and BAALC genes in the bone marrow mononuclear cells of patients with acute myeloid leukemia(AML). Methods: 90 cases of adult AML were selected as the subjects. All the patients were treated with anthracycline induced chemotherapy combined with ara cytarabine. The expression of ERG,MDR1, BAALC gene in bone marrow mononuclear cells was detected by real-time quantitative fluorescence quantitative PCR technique,and the relationship between the expression of ERG, MDR1, BAALC gene and clinical characteristics, risk stratification, treatment efficacy and survival rate of AML patients were analyzed. Results: The expression of ERG, MDR1 and BAALC genes in AML patients were strongly expressed. There was no significant relationship between the expression of three factor and the clinical index such as white blood cells, platelets, etc(P>0.05). There were significant differences between the expressions of ERG, MDR1 and BAALC(P<0.05)corresponding to the stratification of different risk degrees(P<0.05), the expression of ERG, MDR1 and BAALC in the middle and high group were higher than those of the low group. In relation to the effect of treatment and the survival rate, the CR(93.1%%, 89.6%) and OS(56.5%, 66.7%) of ERG and MDR1 low expression group were higher than those of the higher expression group with CR(61.4%,81.3%) and OS(56.5%, 66.7%)(P<0.05). There was no difference in the CR and the survival rate of OS with different expression of BAALC(P >0.05). Conclusion: The expressions of REG, MDR1 and BAALC gene in the bone marrow mononuclear cells of AML patients are negatively correlated with the risk degrees, curative effect and survival rate. REG and MDR1 are sensitive to AML, and BAALC is less sensitive. The combined detection of the expression of REG, MDR1, BAALC gene may improve the accuracy of risk stratification, curative effect and prognosis of AML patients. [ABSTRACT FROM AUTHOR]

Brain and acute leukemia, cytoplasmic (BAALC) and ETS-related gene (ERG) expression levels are independent prognostic factors for acute myeloid leukemia (AML); however, their prognostic impacts on AML patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) require further investigation. We studied 71 de novo AML patients treated with allo-HSCT and defined low and high expressers according to the median expression levels of BAALC and ERG at diagnosis respectively. High BAALC expression was associated with wild-type NPM1 (P = 0.000) and RUNX1 mutations (P = 0.027). High ERG expression was associated with FLT3-ITD absence (P = 0.003) and wild-type NPM1 (P = 0.001). BAALC and ERG expression levels were significantly correlated with each other (P = 0.001). Survival analyses including Kaplan-Meier curves and univariate and multivariate analysis consistently reported that there were no significant differences for both event-free survival (EFS) and overall survival (OS) (all P > 0.1), between high versus low BAALC and ERG expressers. Our study suggested that despite of their well-known adverse role in prognosis of AML, neither BAALC nor ERG expression levels at diagnosis had effect on survival of AML patients who underwent allo-HSCT. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) is recognized as one of the most common types of leukemia among adults. This condition is characterized by the uncontrolled proliferation of myeloid progenitors, affecting the normal function of different systems in the human body. Various factors such as genetic abnormalities, exposure to chemicals, and viruses can induce AML. Expression of NPM1, CEBPA, MN1, and BAALC genes is among important genetic factors affecting AML prognosis and diagnosis. The aim of this study was to assess amount of BAALC gene expression in AML patients and its relation to survival rate. This case-control study was performed at Mashhad University of Medical Sciences, Mashhad, Iran. 56 AML patients and 56 healthy individuals were participated in this research. The level of BAALC gene expression was assessed by real-time polymerase chain reaction (RT-PCR) method; GPI gene was used as the control. For statistical analysis, SPSS version 21 was applied. P-value less than 0.05 was considered statistically significant. In total, 55.3% and 44.7% of the participants were male and female, respectively. BAALC gene up- and down-regulation was reported in 28.6% and 71.4% of AML cases, respectively. BAALC gene expression and hematological parameters were significantly different between the two groups (p< 0.05). Based on the findings, the survival rate was estimated at 31 and 39 months in patients with BAALC up- and down-regulation, respectively. BAALC gene over expression could be considered as a predictive factor for poor prognosis and reduced survival in AML patients. [ABSTRACT FROM AUTHOR]

Background:Brain and Acute Leukemia Cytoplasmic (BAALC) is a gene which its expression is confined to progenitor cells; therefore, no expression has been illustrated in mature cells of bone marrow or white blood cells (WBC). In addition, high BAALC expression is associated with poor prognosis in Acute Myeloid Leukemia (AML) individuals and is considered as an important risk factor in Cytogenetic Normal Acute Myeloid Leukemia. Materials and Methods: This retrospective study was designed to evaluate prognostic importance of BAALC gene expression in pediatric AML patients. Recently, recognized 114 AML Iranian children with age range of 1-15 years were entered in this study during 2012-2015. Real-Time PCR was applied for BAALC gene. Results: High BAALC gene expression was detected in 47 patients (41.2%) and low expression in 67 patients (58.8%). High BAALC gene expression group (n=47) contained23 males and 24 females. All patients were followed up for 2 years to measure disease prognosis. BAALC expression was a main unfavorable prognostic factor in AML patient's especially normal karyotype. AML cases with high BAALC expression had considerable further cumulative risk after 25 months; it was 39 months in low expressed cases. All of cytogenetic normal acute myeloid leukemias (CN-AML) and high BAALC expressed patients died. High BAALC expression in AML cases was associated with considerable shorter overall survival (OS). Conclusion: According to our findings, BAALC expression is a significance poor prognostic factor in AML patients with normal karyotype. This study suggests new therapeutic strategies to ameliorate the treat rate of AML patients. Further research with longer follow up and larger sample size is required to definite statistical perusals. [ABSTRACT FROM AUTHOR]

High BAALC gene expression has been associated with poor prognosis in cytogenetically normal acute myeloid leukaemia (CN-AML) and has been suggested as a suitable marker for assessing minimal residual disease ( MRD). The purpose of this study was to substantiate these findings by the analysis of a large data set of 632 diagnostic and follow-up samples in 142 intensively treated CN- AML patients. Paired diagnostic/relapse samples of 35 patients revealed stable high BAALC expression in 89%, irrespective of a high proportion of clonal evolution found in 49% of these cases. High BAALC expression, both directly after induction chemotherapy and within 3-6 months after induction chemotherapy, correlated significantly with shorter event-free survival and overall survival. Moreover, 8 of 10 patients displaying high BAALC expression levels after completion of induction therapy as well as 5 of 5 patients exhibiting high BAALC expression levels within 3-6 months after induction chemotherapy experienced relapse with a median of 197 and 101 days, respectively, from sampling to relapse. Thus, BAALC expression-based MRD detection during therapy may be considered a strategy to identify patients at high risk of relapse. [ABSTRACT FROM AUTHOR]

Acute leukemia is the most common cancer in children and involves several factors that contribute to the development of multidrug resistance and treatment failure. According to our recent studies, the BAALC gene is identified to have high mRNA expression levels in childhood acute lymphoblastic leukemia (ALL) and those with multidrug resistance. Several polymorphisms are associated with the expression of this gene. To date, there has been no study on the rs62527607 [GT] single nucleotide polymorphism (SNP) of BAALC gene and its link with childhood acute lymphoblastic and myeloid leukemia (AML). The purpose of this study is to evaluate the prevalence of this polymorphism in pediatric acute leukemia, as well as its relationship with prognosis. DNA samples were extracted from bone marrow slides of 129 children with ALL and 16 children with AML. The rs62527607 [GT] SNP was evaluated using mismatch polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)-based analysis. The association between the SNP alleles and patient disease-free survival was then assessed. The prevalence of the T-allele of rs62527607 [GT] SNP in childhood T-ALL and pre-B-ALL was 28.3% and 11.2%, respectively. In the pre-B-ALL patients, 3 year disease free survival was associated with the GG genotype. Results showed a robust association between the rs62527607 SNP and the risk of relapse in ALL, but not AML, patients. T-ALL patients with the GT genotype had an 8.75 fold higher risk of relapse. The current study demonstrates a significant association between the genotype GT and the polymorphic allele G424T, and introduces this SNP as a negative prognostic factor in children with ALL. [ABSTRACT FROM AUTHOR]

Background: Acute myeloid leukemia (AML) is a malignant disorder involving blood cells, characterized by obstructed or distorted differentiation of hematopoietic stem cells. In cytogenetically normal AML (CN AML), molecular abnormalities in NPM, FLT3, CEBPA, and BAALC genes are observed. Initially, high BAALC (Brain and Acute Leukemia Cytoplasmic gene) expression was introduced in a study on AML cases with trisomy 8. The present systematic review aimed to determine the prognostic value of BAALC expression in CN-AML patients within the age range of 1 month to 15 years. Materials and Methods: In this systematic review, scientific databases including PubMed, Scopus, Embase, ISI, and Cochrane Library were searched. All the evaluated retrospective studies focused on the prognostic value of BAALC expression. Results: Overall, BAALC expression was reported in 30-60% of AML patients (mean=45%). High expression of BAALC gene was reported in M0, M1, and M2 subtypes of pediatric AML. In only one study, in addition to these subtypes, M4 was also reported (12.5% of cases). Conclusion: This systematic review resulted in a significant association between high BAALC expression and poor response to chemotherapy in pediatric AML. However, OS (Overall Survival) and EFS (Event - Free Survival) findings were contradictory, relapse and death increase in the presence of high BAALC expression. Therefore, BAALC expression could be considered as a clinical prognostic marker for the treatment of AML patients. Further efficient prognostic indicators should be identified in order to gather information about therapeutic strategies for AML and risk analysis in these patients. [ABSTRACT FROM AUTHOR]

Several genes with relevant pathogenetic and prognostic value have been identified in patients with myelodysplastic syndromes. Overexpression of WT1 at diagnosis has been associated with increased progression to acute myeloid leukemia and reduced leukemia free survival. Conversely, few data are available on the prognostic value of BAALC gene overexpression in AML and MDS patients. We evaluated the prognostic value of the combined expression of WT1 and BAALC genes at diagnosis in 86 MDS patients who had been stratified according to IPSS and R-IPSS scoring systems. Our results suggest that in the whole group of patients, low levels of both WT1 and BAALC were associated with a favorable outcome (3-year LFS 74.5%, median not reached), whereas patients presenting high expression levels of both genes had the worst prognosis (3-year LFS 0%, median 12 months, p < 0.001). More specifically, molecular profiling was especially useful for intermediate 1 and intermediate-2/high risk groups. This study suggests that evaluating WT1 and BAALC gene expression at diagnosis may improve standard risk stratification and possibly refine the therapeutic approach for MDS patients. [ABSTRACT FROM AUTHOR]

Cytogenetic aberrations are important prognostic factors in acute myeloid leukemia (AML). About 45 % of de novo adult AML and 20 % of pediatric AML lack cytogenetic abnormalities, so identification of predictive molecular markers might improve therapy. Mutation status of FLT3, NPM1 genes and gene expression levels of ERG, BAALC have been postulated as possible prognostic markers in pediatric AML with normal karyotype. Pretreatment blood samples from 47 cytogenetically normal AML patients were analysed for BAALC and ERG expression using real time RT-PCR. The patients were dichotomized at BAALC and ERG mean expression into low and high expression based on the median expression as cutoff. BAALC showed high expression in (24/47; 51.1 %) of patients and ERG high expression was detected in (22/47; 46.6 %). With follow-up for 1 year, patients with high BAALC and high ERG had inferior EFS ( P = 0.001, P = 0.017 respectively), overall survival ( P = 0.001, 0.08 respectively), and low rates of induction remission ( P = 0.001, P = 0.0017 respectively) as compared to those with low expression. Also there was significant positive association between high expression of BAALC; ERG and FLT-ITD mutations ( P = 0.016; P = 0.007 respectively). Multivariable analysis confirmed that high BAALC expression is an independent risk factor for EFS [HR for EFS 1.9(1.04-3.46) P = 0.037]; and OS [HR OS 1.55(1.7-3.36) P = 0.03]. In conclusion: Over expression of BAALC could predict adverse clinical outcome and may define important risk factor in cytogenetically normal pediatric AML. [ABSTRACT FROM AUTHOR]

To investigate the expression of brain and acute leukemia, cytoplasmic ( BAALC) and analyze its clinical significance in Chinese de novo acute myeloid leukemia (AML). Real-time quantitative PCR (RQ-PCR) was carried out to detect BAALC transcript level in 121 de novo AML patients and 41 normal controls. BAALC transcript level in AML patients was significantly up-regulated compared with normal controls ( P < 0.001). Patients with high BAALC expression had significantly older age than those with low BAALC expression ( P = 0.021). The percentage of blasts in bone marrow of the BAALC high-expressed patients was significantly higher than that in the low-expressed patients ( P < 0.001). The incidence of BAALC overexpression was significantly higher in M0/M1 (8/9, 89 %) and M2 subtypes (33/48, 68 %) than in M3 subtype (6/27, 22 %) ( P < 0.001). The frequency of IDH1/2 wild type in CN-AML patients with high BAALC expression was significantly higher than those with low BAALC expression ( P = 0.031). BAALC high-expressed patients had a significantly lower complete remission than low-expressed patients in both entire AML cohort and CN-AML ( P = 0.013 and 0.029, respectively). Furthermore, both whole AML cohort and CN-AML patients with high BAALC expression showed a shorter overall survival than those with low BAALC expression ( P = 0.002 and 0.008, respectively). Multivariate analysis confirmed high BAALC expression as an independent adverse prognostic factor in both AML and CN-AML patients. Our study indicates that overexpression of BAALC serves as an independent prognostic biomarker in both whole AML cohort and CN-AML patients. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia with normal cytogenetics (CN-AML) is the largest group of AML patients which is associated with a variegated patient outcome. Multiple molecular markers have been used to risk-stratify these patients. Estimation of expression of BAALC gene (Brain and Acute Leukemia, Cytoplasmic) mRNA level is one of the predictive markers which has been identified in multiple studies. In this study, we examined the clinical and prognostic value of BAALC gene expression in 149 adult CN-AML patients. We also utilized multi-omics databases to ascertain the association of BAALC gene expression with comprehensive molecular and clinicopathologic features in AML. BAALC overexpression was associated with CD34 positivity on leukemic blasts (p = 0.0026) and the absence of NPM1 gene mutation (p < 0.0001), presence of RUNX1 gene mutation (p < 0.001) and poor patient outcomes, particularly in NPM1 –wild type/FLT3-ITD negative adult CN-AML patients. Additionally, BAALC expression was associated with the alteration of methylation of its promoter. Further, pathway analysis revealed that BAALC expression is correlated with MYC targets and Ras signalling. We conclude that high BAALC expression associates with poor patient outcome in NPM1 –wild type/FLT3-ITD negative adult CN-AML patients. • CN-AML is the largest group of AML patients which is associated with a variegated patient outcome. • We examined the clinical and prognostic value of BAALC gene expression in 149 adult CN-AML patients. • Multi-omics data was used to determine the association of BAALC expression with clinical and molecular attributes in AML. • High BAALC expression was associated with poor patient outcome in NPM1 –wild type /FLT3-ITD negative adult CN-AML patients. • Associated distinct gene expression profiles can help in the identification of novel therapeutic agents in AML. [ABSTRACT FROM AUTHOR]

Treatment optimization in acute myeloid leukemia requires the accurate assignment of patients at diagnosis to specific risk groups to guide subsequent risk-adapted treatment stratification. In this study, we have evaluated the impact of expression of the gene BAALC in conjunction with MDR1 in AML with intermediate cytogenetic risk group to more precisely define risk assessment. Low MDR1/high BAALC, high MDR1/low BAALC, and high MDR1/high BAALC expressers demonstrated a similar clinical outcome with CR rate being 68.75-75% and relapse rate being 40-50% and therefore could be considered as a "combined group". In contrast, low expression of both BAALC and MDR1 identifies an intermediate cytogenetic risk group a distinctly favorable outcome, with higher CR rate being 93.3%, lower relapse rate being 7.1%, and longer OS being 50.3% than that of the "combined group". Moreover, low MDR1/low BAALC expressers in the intermediate cytogenetic risk group also demonstrated a comparable clinical outcome with patients in the favorable-risk group. Thus low MDR1/low BAALC expression identifies a subgroup of intermediate cytogenetic risk AML patients with a remarkably good long-term outcome achieved by chemotherapy alone. [ABSTRACT FROM AUTHOR]

Data for 125 patients with cytogenetically normal acute myeloid leukemia (CN-AML) regarding BAALC and combinatorial molecular markers at diagnosis were evaluated. Fewer patients with higher BAALC expression at diagnosis achieved a complete remission (CR) (49.2 vs. 75.8%, p = 0.002) after the first cycle of chemotherapy, and there were more primary refractory cases (37.3 vs. 18.2%, p = 0.017). In a combinatorial analysis, FLT3-ITD-positive patients with higher BAALC showed more refractoriness and the worst overall survival (OS) ( p < 0.001) and disease-free survival (DFS) ( p < 0.001) in CN-AML. When NPM1-mutated CN-AML was combined with either FLT3-ITD mutation or higher BAALC expression, both OS ( p = 0.043) and DFS ( p = 0.008) were worse; when combined with both, it showed the worst OS ( p < 0.001) and DFS ( p = 0.004). Higher BAALC expression and FLT3-ITD mutation, both individually and in combination, were associated with worse survival outcomes in CN-AML, and this was also applicable in NPM1-mutated CN-AML, known as a favorable-risk group. [ABSTRACT FROM AUTHOR]

Objective: We performed comprehensive proteomic analyses of articular cartilage by using the isobaric tags for relative and absolute quantitation (iTRAQ) method, and searched for candidate biomarkers for osteoarthritis (OA). Methods: Articular cartilage was collected from patients with OA or femoral neck fracture for the control group. Molecular variations were detected by the ITRAQ method, and quantitative analyses were performed by western blot. Results: Using the iTRAQ method, we identified 76 proteins with different expression levels in OA patients and the control group. Among these proteins, we selected LECT2 (leukocyte cell-derived chemotaxin-2), BAALC (brain and acute leukemia, cytoplasmic), and PRDX6 (peroxiredoxin-6), which had not been reported as biomarkers for OA. Conclusions: Use of these proteins in combination with conventional OA biomarkers may better reflect the grade and prognosis of OA. [ABSTRACT FROM AUTHOR]

Simultaneous quantitative measurement of mRNA of the WT1, BAALC, EVI1, PRAME and HMGA2 genes in whole blood samples reflects the specific pathological proliferative activity in acute leukemia and their ratio is promising as a diagnostic marker. The transcriptome profile of acute leukemia cells is usually assessed using NGS or microarray techniques after a preliminary procedure for isolation of mononuclear cells. However, the results of using the multiplex PCR reaction for the simultaneous determination of all above mRNAs in whole blood samples have not been published so far. Determination of mRNA of WT1, BAALC, EVI1, PRAME and HMGA2 genes in venous blood level samples by multiplex RT-PCR. The study included 127 blood samples from patients who diagnosis of acute leukemia was subsequently confirmed. In the comparison group, 87 samples of patients without oncohematological diagnosis were selected, including 31 samples (K1) with a normal blood formula and 56 samples (K2) with a violation of the cellular composition - anemia, leukocytosis and thrombocytopenia. RNA isolation and reverse transcription were performed using the Ribozol-D and Reverta-L kits (TsNIIE, Russia). Determination of the mRNA expression level of the WT1, BAALC, EVI1, PRAME and HMGA2 genes by multiplex real-time PCR using a homemade multiplex PCR kit. The mRNA level was characterized by high interindividual variation and did not correlate with the rate of circulating leukocytes or blood blasts. Expression of WT1 mRNA was observed in whole blood only in one patient from the control group and in 112 (88%) patients with leukemia and was combined with a decrease in the level of HMGA2 mRNA expression and BAALC mRNA values. In contrast to the control groups, patients with leukemia had higher levels of BAALC mRNA in AML and ALL, increased PRAME mRNA in AML and APL, but lower levels of HMGA2 in APL., Competing Interests: The authors declare no conflict of interest.

No consecutive analysis of BAALC and WT1 expressions associated with core-binding factor AML ( CBF- AML) from diagnosis to hematopoietic stem cell transplantation ( HSCT) has yet been reported. We investigated BAALC and WT1 expressions using a method of real-time quantitative polymerase chain reaction ( RQ- PCR) at diagnosis, after induction chemotherapy, at pre- HSCT, and at post- HSCT period in 45 consecutive patients [t(8,21) ( n = 28), inv(16) (n = 17)], who received HSCT as a post-remission treatment. BAALC and WT1 RQ- PCR decrement ratio ( DR) was also calculated at post-induction chemotherapy, at pre- HSCT, and at post- HSCT compared with the diagnostic level. Higher BAALC expression at diagnosis showed significantly inferior OS ( P = 0.031), EFS ( P = 0.011), and higher CIR ( P = 0.002) rates. At post- HSCT, both higher BAALC and WT1 expressions showed significantly inferior OS ( P = 0.005, 0.016), EFS ( P = 0.002, 0.006), and higher CIR ( P = 0.001, 0.003) rates. A subgroup of t(8;21) showing higher BAALC and WT1 expressions at post- HSCT were also associated with inferior OS ( P = 0.018, 0.015) and higher CIR rates ( P = 0.019, 0.011). While BAALC DR showed no significant results on outcomes, WT1 DR more than 2-log at post- HSCT showed significantly lower CIR rate ( P = 0.028). This study showed that higher post- HSCT BAALC and WT1 expressions in patients with CBF- AML may be good markers of minimal residual disease for the prediction of survival and relapse after HSCT. [ABSTRACT FROM AUTHOR]

Abstract: We evaluated the prognostic value of BAALC expression in 86 patients with acute promyelocytic leukemia (APL). At 10 years, the overall survival (OS) was 66% in all patients and 75% in patients who achieved a complete remission (CR). Patients in the BAALClow group showed an OS of 87% as compared to 60% in the BAALChigh group (p =0.019). This difference was more pronounced in treatment responders (92% vs. 70%; p =0.035). In multivariate analyses low BAALC expression retained its prognostic relevance. In conclusion, BAALC expression analysis might be useful in further risk stratification in APL patients. [Copyright &y& Elsevier]

Abstract: BAALC expression is an indicator of aggressiveness in acute myelogenous leukemia (AML). Overexpression of this gene is associated to poor of clinical outcome. It is known that post-translational histone modifications control gene transcription. Thus, here we have investigated BAALC expression and post-translational histone modifications in leukemia cell lines. We show that Kasumi-6 and Kyo cells have high and low BAALC mRNA levels, respectively. Moreover, we demonstrate that these cell lines present distinct profiles in terms of histone post-translational modifications (H3K9K14 acetylation, H3K4 trimethylation and H3K23 trimethylation) at the level of BAALC promoter. These findings, in light of recent data on how histone post-translational modifications control gene expression, indicate that BAALC gene is “paused” and that in leukemia cells its transcription can be activated or repressed by mechanisms acting on epigenetic marks. [Copyright &y& Elsevier]

Brain and acute leukemia, cytoplasmic (BAALC) is a novel molecular marker indicating an inferior outcome in acute myeloid leukemia (AML) with normal cytogenetics. The biological function of BAALC is largely unknown. In this study, BAALC gene expression in an acute myeloid leukemia cell line KG1a was knocked down by a small hairpin RNA (shRNA). The expression of BAALC mRNA and protein in the knockdown cells was significantly inhibited. The proliferation and apoptosis status in the knockdown cells were investigated. The growth curves and FACS analysis demonstrated that BAALC gene knockdown resulted in decreased proliferation and enhanced apoptosis in KG1a cells. These results indicated that BAALC may act as an adverse prognostic factor through prompting proliferation and inhibiting apoptosis in leukemia cells. [ABSTRACT FROM AUTHOR]