BAALC expression predicts clinical outcome of de novo acute myeloid leukemia patients with normal cytogenetics: a Cancer and Leukemia Group B Study.
Cytogenetic aberrations are important prognostic factors in acute myeloid leukemia (AML). Of adults with de novo AML, 45% lack cytogenetic abnormalities, and identification of predictive molecular markers might improve therapy. We studied the prognostic impact of BAALC (Brain And Acute Leukemia, Cytoplasmic), a novel gene involved in leukemia, in 86 de novo AML patients with normal cytogenetics who were uniformly treated on Cancer and Leukemia Group B 9621. BAALC expression was determined by comparative real-time reverse transcriptase-polymerase chain reaction in pretreatment blood samples, and patients were dichotomized at BAALC's median expression into low and high expressers. Low expressers had higher white counts (P =.03) and more frequent French-American-British M5 morphology (P =.007). Compared to low expressers, high BAALC expressers showed significantly inferior overall survival (OS; median, 1.7 vs 5.8 years, P =.02), event-free survival (EFS; median, 0.8 vs 4.9 years, P =.03), and disease-free survival (DFS; median, 1.4 vs 7.3 years, P =.03). Multivariable analysis confirmed high BAALC expression as an independent risk factor. For high BAALC expressers the hazard ratio of an event for OS, EFS, and DFS was respectively 2.7, 2.6, and 2.2. We conclude that high BAALC expression predicts an adverse prognosis and may define an important risk factor in AML with normal cytogenetics.
The Ohio State University, Starling-Loving Hall, 320 West 10th Ave, Columbus, OH 43210, USA.
Claudia D
CD
Baldus
Stephan M
SM
Tanner
Amy S
AS
Ruppert
Susan P
SP
Whitman
Kellie J
KJ
Archer
Guido
G
Marcucci
Michael A
MA
Caligiuri
Andrew J
AJ
Carroll
James W
JW
Vardiman
Bayard L
BL
Powell
Steven L
SL
Allen
Joseph O
JO
Moore
Richard A
RA
Larson
Jonathan E
JE
Kolitz
Albert
A
de la Chapelle
Clara D
CD
Bloomfield
D000208:Acute Disease; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006801:Humans; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000453:epidemiology / Q000235:genetics* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000235:genetics*; D011237:Predictive Value of Tests; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D016896:Treatment Outcome
C442828:BAALC protein, human; D005819:Genetic Markers; D009363:Neoplasm Proteins; D003561:Cytarabine; D005047:Etoposide; D003630:Daunorubicin