Journal of Blood Disorders & Transfusion

Abstract

BAALC Gene Expression in Adult B-precursor Acute Lymphoblastic Leukemia: Impact on Prognosis

Mona M. Taalab, Iman M. Fawzy, Enas F. Goda and Eman M. Abdul Salam

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 BCRABL+ 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-ABL- subgroup (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.