High BAALC expression predicts chemoresistance in adult B-precursor acute lymphoblastic leukemia.

Abstract:

:Overexpression of BAALC is an adverse prognostic factor in adults with cytogenetically normal acute myeloid leukemia and T-cell acute lymphoblastic leukemia (ALL). Here, we analyzed the prognostic significance of BAALC in B-precursor ALL. BAALC MRNA expression was determined in 368 primary adult B-precursor ALL patients enrolled on the 06/99 and 07/03 GMALL trials. Patients were grouped into tertiles according to BAALC expression (T1-T3). Higher BAALC expression (T3 vs T2 vs T1) was associated with higher age (P < .001), a higher white blood cell count (P = .008), CD34 (P = .001), BCR-ABL (P < .001), and MLL-AF4 (P < .001). Higher BAALC expression predicted primary therapy resistance in the overall cohort (P = .002) and in the BCR-ABL(-) and MLL-AF4(-) subgroup (P = .01). In BCR-ABL(-) and MLL-AF4(-) patients, higher BAALC expression was associated with a shorter overall survival (OS; 5-year OS: T3, 38%; T2, 52%; T1, 70%; P = .004) and independently predicted OS in multivariate models (P = .03). Gene-expression profiling revealed an up-regulation of stem cell markers and genes involved in chemoresistance (TSPAN7 and LYN) in the high BAALC group. Thus, high BAALC expression is associated with an immature, chemoresistant leukemic phenotype and identifies patients with inferior OS. Determination of BAALC might contribute to risk assessment of molecularly undefined adult B-precursor ALL.

journal_name

Blood

journal_title

Blood

authors

Kühnl A,Gökbuget N,Stroux A,Burmeister T,Neumann M,Heesch S,Haferlach T,Hoelzer D,Hofmann WK,Thiel E,Baldus CD

doi

10.1182/blood-2009-09-241943

subject

Has Abstract

pub_date

2010-05-06 00:00:00

pages

3737-44

issue

18

eissn

0006-4971

issn

1528-0020

pii

blood-2009-09-241943

journal_volume

115

pub_type

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