High receptor tyrosine kinase (FLT3, KIT) transcript versus anti-apoptotic (BCL2) transcript ratio independently predicts inferior outcome in pediatric acute myeloid leukemia

Abstract

Objective In acute myeloid leukemia (AML), simultaneous expression of proliferative (FLT3, KIT) and anti-apoptotic genes (BCL2) is unknown. The aim of the study was to prospectively evaluate proliferative and anti-apoptotic gene transcripts, their interrelationship and impact on the outcome in pediatric AML patients. Methods We assessed proliferative and anti-apoptotic gene transcripts by Q-polymerase chain reaction (TaqMan probe) in 64 consecutive pediatric AML patients. Survival data was analyzed by Kaplan–Meier curves followed by log rank test to compare statistical significance between groups. Stepwise multivariable Cox regression method was used to evaluate independent prognostic factors. Results In univariate analysis, transcript ratio of FLT3/BCL2 and FLT3 + KIT/BCL2 significantly predicted event free survival (EFS) (< 0.01 and < 0.01 respectively) and overall survival (OS) (< 0.01 and < 0.01 respectively). In stepwise Cox-regression model, high white blood cell count and high FLT3 + KIT/BCL2 ratio predicted EFS (HR: 2.2 and 2.3); high hemoglobin and high FLT3 + KIT/BCL2 ratio predicted OS (HR: 0.45 and 3.85). Prognostic index (PI) was calculated using the hazard coefficient of independent prognostic factors; at 57.3 months, predicted OS of patients with the highest PI of 1.8 was 8% versus 73% for the lowest PI of − 0.3. The mean PI of patients who died was 1.8 ± 0.72 versus 0.54 ± 0.70 for those who are alive, P = 0.004. Conclusions This first study showed that individual expression of proliferative and anti-apoptotic transcripts is not as important in AML patients, rather their interrelationship and relative level probably determines the outcome.