title: 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.
authors.affiliation: Medizinische Klinik III, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, 12203 Berlin, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Kühnl
authors.forename: Nicola
authors.initials: N
authors.lastname: Gökbuget
authors.forename: Andrea
authors.initials: A
authors.lastname: Stroux
authors.forename: Thomas
authors.initials: T
authors.lastname: Burmeister
authors.forename: Martin
authors.initials: M
authors.lastname: Neumann
authors.forename: Sandra
authors.initials: S
authors.lastname: Heesch
authors.forename: Torsten
authors.initials: T
authors.lastname: Haferlach
authors.forename: Dieter
authors.initials: D
authors.lastname: Hoelzer
authors.forename: Wolf-Karsten
authors.initials: WK
authors.lastname: Hofmann
authors.forename: Eckhard
authors.initials: E
authors.lastname: Thiel
authors.forename: Claudia D
authors.initials: CD
authors.lastname: Baldus
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000378:metabolism; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; C442828:BAALC protein, human; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion