Originally published as JCO Early Release 10.1200/JCO.2005.01.6253 on January 17 2006

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BAALC Expression and FLT3 Internal Tandem Duplication Mutations in Acute Myeloid Leukemia Patients With Normal Cytogenetics: Prognostic Implications

From the Charité, Universitätsmedizin Berlin, Campus Benjamin Franklin, Medizinische Klinik III, Berlin; Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Medizinische Klinik I; Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Deutsche Studieninitiative Leukämie Statistical Group, Dresden, Germany; and The Ohio State University, Comprehensive Cancer Center, Columbus, OH

Address reprint requests to Claudia D. Baldus, MD, Charité, Universitätsmedizin Berlin, Campus Benjamin Franklin, Department of Hematology, Oncology and Transfusion Medicine, Hindenburgdamm 30, 12203 Berlin, Germany; e-mail: claudia.baldus{at}charite.de

PURPOSE: Evaluate the impact of BAALC (brain and acute leukemia, cytoplasmic), a gene whose expression has been associated with adverse outcome in acute myeloid leukemia (AML) with normal cytogenetics, and FLT3 internal tandem duplication (ITD) mutations as independent prognostic factors in a larger study.

PATIENTS AND METHODS: BAALC expression was determined by real-time reverse transcriptase polymerase chain reaction in pretreatment blood samples of 307 adults 60 years of age with AML with normal cytogenetics. Patients were dichotomized at BAALC's median expression into low and high expressers. The FLT3 ITD mutant:wild-type ratio was determined by fragment analysis.

RESULTS: Compared with low-BAALC patients, high-BAALC patients had a higher rate of primary resistant leukemia (16% v 6%; P = .006). High BAALC expression was associated with a higher cumulative incidence of relapse (CIR; P = .018) and an inferior overall survival (OS; 3-year OS, 36% v 54%; P = .001). On multivariable analysis, high BAALC was independently predictive of resistant disease (P = .019), and high BAALC as well as a high FLT3 mutant:wild-type ratio were confirmed as the only factors predicting a high CIR (BAALC, P = .03; FLT3, P = .01) and inferior OS (BAALC, P = .001; FLT3, P = .012).

CONCLUSION: This study strengthens BAALC expression as one of the most important prognostic factors in AML patients with normal cytogenetics. BAALC expression and FLT3 mutation status should assist in tailoring induction and postremission therapies.

Supported by Leukemia Clinical Research Foundation (C.D.Bloomfield) and supported by grants from the Deutsche Krebshilfe and the Bundesministerium f. Bildung u. Forschung (Kompetenznetzwerk "Akute und Chronische Leukämien"; G.E.).

C.D. Baldus and C. Thiede contributed equally to this work.

Terms in blue are defined in the glossary, found at the end of this article and online at www.jco.org.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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