BAALC expression and FLT3 internal tandem duplication mutations in acute myeloid leukemia patients with normal cytogenetics:: Prognostic implications

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 BAALCs 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 AM L patients with normal cytogenetics. BAALC expression and FLT3 mutation status should assist in tailoring induction and postremission therapies.