Prognostic Implication of BAALC Gene Expression in Adult Acute Myeloid Leukemia (original) (raw)
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Blood cancer journal, 2014
High brain and acute leukemia, cytoplasmic (BAALC) expression defines an important risk factor in cytogenetically normal acute myeloid leukemia (CN-AML). The prognostic value of BAALC expression in relation to other molecular prognosticators was analyzed in 326 CN-AML patients (<65 years). At diagnosis, high BAALC expression was associated with prognostically adverse mutations: FLT3 internal tandem duplication (FLT3-ITD) with an FLT3-ITD/FLT3 wild-type (wt) ratio of 0.5 (P=0.001), partial tandem duplications within the MLL gene (MLL-PTD) (P=0.002), RUNX1 mutations (mut) (P<0.001) and WT1mut (P=0.001), while it was negatively associated with NPM1mut (P<0.001). However, high BAALC expression was also associated with prognostically favorable biallelic CEBPA (P=0.001). Survival analysis revealed an independent adverse prognostic impact of high BAALC expression on overall survival (OS) and event-free survival (EFS), and also on OS when eliminating the effect of allogeneic stem ...
American Journal of Hematology, 2013
Overexpression of brain and acute leukemia cytoplasmic (BAALC) gene confers poor prognosis in cytogenetically normal acute myeloid leukemia (AML) patients, while less defined is its role in AML with abnormal karyotype. We evaluated the effect of BAALC overexpression on outcome of 175 adult AML patients with different cytogenetic risks. Karyotype was favorable in 13, intermediate in 117 and unfavorable in 45 patients, respectively. Quantitative BAALC expression was determined by real-time PCR, with cut off value set at 50th percentile. BAALC was overexpressed in 87/175 (50%) patients, without association with cytogenetic status. High BAALC was associated with unmutated NPM (P 5 0.006) and CD34 positivity (P < 0.0001). Complete remission (CR) was attained in 111 patients (63%), and was maintained at 5 years in 52 6 7%. BAALC overexpression had a negative impact on CR achievement (P 5 0.04), while did not influence relapse probability. Median survival was 22 months with a 5-years overall survival (OS) of 35%. Factors with a negative impact on OS were older age (P 5 0.0001), unfavorable cytogenetic (P 5 0.005), ABCG2 overexpression (P 5 0.03) and high BAALC levels (P 5 0.01). We observed a worse outcome in patients with high BAALC expression through all cytogenetic risk categories: 5-years OS was 100% vs. 71% in patients with favorable cytogenetics (P 5 0.05), 55% vs. 40% in cases with intermediate karyotype (P 5 0.04) and 34% vs. 23% in unfavorable cytogenetic subgroup (P 5 0.02). BAALC overexpression identified AML patients with poor prognosis in all cytogenetic groups. Though relatively rare, BAALC positivity in patients with favorable or unfavorable karyotype significantly worsened survival. Am. J. Hematol. 88:848-852,
International Journal of Advanced Research (IJAR), 2019
Baalc expression is an indicator of aggressiveness in aml. Overexpression of this gene is associated to poor of clinical outcome.highbaalc expression was independent associated with lower cr,shorterefs and shorter os. Aim of work:the study aimed to is assess baalc expression levels in acute myeloid leukaemia patients and then evaluate its prognostic significance. Subjects and methods:this study was conducted on 56 adult patients who were admitted to the clinical oncology unit including 35 males and 22 females.for all patients complete blood picture, ldh , bone marrow aspiration , immunophenotyping , cytogenetic analysis and assessment of baalc gene expression by real time pcr were done.results:the prognostic value for baalc gene expression was evaluated.the validity of baalc gene expression as a prognostic marker for aml showed that the sensitivity and specificity were 86.1% and 80% respectively. The relation between baalc gene expression and overall survival in aml patients revealed that patients with baalc ≥ 2.11 had shorter os than did those with lower level baalc.
Annals of Hematology, 2010
We have analyzed brain and acute leukemia, cytoplasmic (BAALC) gene expression and other genetic markers (ERG, EVI1, MN1, PRAME, WT1, FLT3, and NPM1 mutations) in 127 intermediate-risk acute myeloid leukemia (AML) patients: 98 cytogenetically normal and 29 with intermediate-risk cytogenetic alterations. High versus low BAALC expressers showed a higher refractoriness to induction treatment (31% vs 10%; p=.005), lower complete remission rate after salvage therapy (82% vs 97%; p=.010), and lower 3-year overall (23% vs 58%, p<.001) and relapse-free survival (26% vs 52%, p=.006). Similar results were found when cytogenetic subgroups were analyzed separately. Multivariate models confirmed the unfavorable prognosis of this marker. In conclusion, BAALC is a relevant prognostic marker in intermediaterisk AML.
Indian Journal of Hematology and Blood Transfusion, 2014
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.
Indian Journal of Medical and Paediatric Oncology, 2020
Background: Brain and acute leukemia, cytoplasmic (BAALC) gene is identified on chromosome 8q22.3 and implicated in normal hematopoiesis. BAALC gene overexpression is associated with poor outcome. Methods: We aimed to evaluate BAALC expression in de novo Egyptian acute myeloid leukemia (AML) cases and determine its prognostic value. We recruited 70 patients with de novo AML diagnosed and treated at clinical pathology and medical oncology departments, fulfilling inclusion criteria in our prospective study and evaluated BAALC expression level. Patients received induction therapy. The Institutional Review Board approved our study. Results: The mean age was 39.2 years ± 11.87, (18–60) with a male/female ratio of 3/2. The cutoff value of BAALC as a prognostic factor was 2.11 with sensitivity (86.1%), specificity (80%), positive predictive value (88.6%), and negative predictive value (76.2%.) (P < 0.001), 43 (61.4%) patients had high BAALC expression. Seventy-two percent of patients in...
Risk Assessment in Patients with Acute Myeloid Leukemia and a Normal Karyotype
Clinical Cancer Research, 2005
Purpose: The recognition of a number of leukemiaspecific cytogenetic abnormalities and their role as independent prognostic factors have provided considerable insights into leukemia pathogenesis and have paved the way to adopt risk-adapted treatment. However, f 50% of newly diagnosed acute myeloid leukemia (AML) have a normal karyotype. There has therefore been much interest in identifying molecular markers that could help to improve the prognostic stratification of patients with normal-karyotype AML. Experimental Design: Consecutive untreated AML patients (n = 67) from a single institution all with normal karyotype were analyzed for the presence of mutations in the myeloid transcription factor gene CEBPA (for CCAAT/ enhancer binding protein-A), for internal tandem duplications (ITD) of the tyrosine kinase receptor gene FLT3 (for fms-like tyrosine kinase 3), and for expression of the BAALC gene (for brain and acute leukemia, cytoplasmic). Results: 17.9% of normal-karyotype AML had mutations in the CEBPA gene, and 28.4% had FLT3-ITD; 65.7% (44 of 67) had high BAALC expression and 34.3% (23 of 67) had low BAALC expression. Patients with CEBPA mutations had a very favorable course of their disease. Median diseasefree survival (DFS) and overall survival (OS) were 33.5 and 45.5 months, respectively, compared with 10 (e.g., 12 months in patients without CEBPA mutations; P = 0.0017; P = 0.0007). AML patients with FLT3-ITD had significantly shorter median DFS (P = 0.0328) and OS (P = 0.0148) than patients without FLT3-ITD. High BAALC expression predicted for a shorter DFS (P = 0.0152) and OS (P = 0.0210) compared with AML with low BAALC expression; 53.7% of normal-karyotype AML had neither FLT3-ITD nor CEBPA mutations. We found that high BAALC expression in normalkaryotype AML with neither FLT3-ITD nor CEBPA mutations (18 of 67) indicates adverse prognosis for both DFS and OS (P = 0.0001; e.g., P = 0.0001) compared with the group with low BAALC expression and absent FLT3-ITD and CEBPA mutations (18 of 67). Thus, BAALC expression represents a novel prognostic marker particularly for normal-karyotype AML patients with neither FLT3-ITD nor CEBPA mutations. Conclusions: Assessment of CEBPA mutations, FLT3-ITD, and BAALC expression permits to split normalkaryotype AML into clinically distinct subgroups.
2011
In order to identify acute myeloid leukemia (AML) CD34 þspecific gene expression profiles, mononuclear cells from AML patients (n ¼ 46) were sorted into CD34 þ and CD34 À subfractions, and genome-wide expression analysis was performed using Illumina BeadChip Arrays. AML CD34 þ and CD34 À gene expression was compared with a large group of normal CD34 þ bone marrow (BM) cells (n ¼ 31). Unsupervised hierarchical clustering analysis showed that CD34 þ AML samples belonged to a distinct cluster compared with normal BM and that in 61% of the cases the AML CD34 þ transcriptome did not cluster together with the paired CD34 À transcriptome. The top 50 of AML CD34 þ-specific genes was selected by comparing the AML CD34 þ transcriptome with the AML CD34 À and CD34 þ normal BM transcriptomes. Interestingly, for three of these genes, that is, ankyrin repeat domain 28 (ANKRD28), guanine nucleotide binding protein, alpha 15 (GNA15) and UDP-glucose pyrophosphorylase 2 (UGP2), a high transcript level was associated with a significant poorer overall survival (OS) in two independent cohorts (n ¼ 163 and n ¼ 218) of normal karyotype AML. Importantly, the prognostic value of the continuous transcript levels of ANKRD28 (OS hazard ratio (HR): 1.32, P ¼ 0.008), GNA15 (OS HR: 1.22, P ¼ 0.033) and UGP2 (OS HR: 1.86, P ¼ 0.009) was shown to be independent from the well-known risk factors FLT3-ITD, NPM1c þ and CEBPA mutation status.