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


METHODS
BAALC expression was determined by real-time reverse transcriptase polymerase chain reaction in pretreatment blood samples of 307 adults <or= 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).


CONCLUSIONS
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.
Baldus
Claudia D
CD
Charité, Universitätsmedizin Berlin, Campus Benjamin Franklin, Medizinische Klinik III, Berlin, Germany. claudia.baldus@charite.de
Thiede
Christian
C
Soucek
Silke
S
Bloomfield
Clara D
CD
Thiel
Eckhard
E
Ehninger
Gerhard
G
D000328:Adult; D004252:DNA Mutational Analysis; D019008:Drug Resistance, Neoplasm; D005260:Female; D020440:Gene Duplication; D020869:Gene Expression Profiling; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics*; D010347:Patient Care Planning; D016133:Polymerase Chain Reaction; D011379:Prognosis; D016019:Survival Analysis; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
C442828:BAALC protein, human; D009363:Neoplasm Proteins; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3