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

Blood Cells Mol Dis. 2015 Jan;54(1):56-64. doi: 10.1016/j.bcmd.2014.07.019. Epub 2014 Sep 15.

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.

Keywords: Acute myeloid leukemia; BCL2; FLT3; KIT; Real time PCR.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Leukemic*
  • Humans
  • Infant
  • Leukemia, Myeloid, Acute / metabolism*
  • Leukemia, Myeloid, Acute / mortality*
  • Male
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis*
  • Proto-Oncogene Proteins c-kit / biosynthesis*
  • Survival Rate
  • fms-Like Tyrosine Kinase 3 / biosynthesis*

Substances

  • BCL2 protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • FLT3 protein, human
  • Proto-Oncogene Proteins c-kit
  • fms-Like Tyrosine Kinase 3