BAALC Gene Expression in Adult B-precursor Acute Lymphoblastic Leukemia: Impact on Prognosis (original) (raw)

2014, Journal of Blood Disorders & Transfusion

Background: Adult B-precursor acute lymphoblastic leukemia (ALL) remains a major therapeutic challenge. Various molecular markers have extensively been investigated to improve its risk profile characterization, disease progression and resistance to treatment. Aim: To analyze the brain and acute leukemia, cytoplasmic (BAALC) gene expression and to assess its prognostic impact in B-precursor ALL. Subjects and Methods: BAALC mRNA expression was analyzed using real time PCR in 200 primary adult B-precursor ALL patients. Patients were grouped into 2 groups according to median BAALC expression. Results: High BAALC expression was associated with older age (P=0.037), higher white blood cell count (P =0.019), LDH concentration (p=0.007), higher incidence of positive CD34 (P =0.011) and positive BCR-ABL (P=0.011). High BAALC expression was associated with primary therapy resistance in the overall cohort (P = 0.001), in BCR-ABL − and BCR-ABL + subgroups (P = 0.039, 0.003 respectively). Multivariate analysis showed that BAALC expression was an independent risk factor for chemotherapy resistance in the overall cohort (=0.003, OR=3.133, 95% CI=1.482-6.623) and in both BCR-ABL-(p=0.049, OR=2.359, 95%CI=1.004-5.538), and BCR-ABL + subgroups (p=0.014, OR=2.672, 95%CI=1.824-3.326). Higher BAALC expression was associated with a shorter overall survival (OS) (p= 0.010) and disease free survival (DFS) (p<0.001) in the overall cohort, and DFS in BCR-ABLsubgroup (p<0.001). Multivariate analysis showed that higher BAALC expression independently predicted OS and DFS in the overall cohort (P = 0.039, 0.002 respectively) and DFS in BCR-ABL-subgroup (p=0.001). Conclusion: High BAALC expression is associated with refractory disease in adult B-precursor ALL, and predicts shorter OS and DFS. Determination of BAALC expression may contribute to risk stratification of adult B-precursor ALL, and may improve the currently disappointing cure rate.