FLT3 Internal Tandem Duplication Mutation, cMPL and CD34 Expressions Predict Low Survival in Acute Myeloid Leukemia Patients

Ann Clin Lab Sci. 2016 Dec;46(6):592-600.

Abstract

Objectives: To detect FMS-like tyrosine kinase-3 internal tandem duplicate (FLT3 ITD) mutation, Myeloproliferative leukemia virus oncogene (cMPL) and Ephrin A 4 receptor (EphA4) expressions in Acute myeloid leukemia (AML) and their correlation to patient's clinicopathological characteristics and survival.

Methods: RNA was extracted from blood samples of 58 AML patients (39 adults and 19 children) and 20 age and sex matched controls. FLT3 ITD mutation, cMPL and EphA4 expression was studied using RT-PCR and correlated to the clinical and survival data of the patients.

Results: FLT3 ITD mutation, cMPL and EphA4 expression was positive in 35.9%, 76.9% and 56.4% of adult AML patients respectively and in 15.8%, 47.4% and 36.8% of pediatric AML patients respectively. 76.9% of adult and 89.5% of pediatric patients expressed CD33. 64.1 % of adults and 42.1% of children expressed CD34. CD34 expression was significantly associated with both FLT3 ITD mutation and cMPL expression. CD34, FLT3 and cMPL negative cases have significantly higher overall survival than positive cases.

Conclusion: CD34 expression is significantly associated with both FLT3 ITD mutation and cMPL expression which could be used as a marker for low survival. Normal FLT3 and negative expression of CD34 and cMPL may predict a longer overall survival. Further studies are needed to investigate the mechanism that may correlate CD34 to both markers.

Keywords: Acute myeloid leukemia; CD34; EphA4; FLT3 ITD; cMPL; survival.

MeSH terms

  • Adult
  • Antigens, CD34 / genetics*
  • Antigens, CD34 / metabolism
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Child
  • Female
  • Gene Duplication*
  • Gene Expression Regulation, Leukemic*
  • Humans
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / pathology
  • Male
  • Mutation / genetics*
  • Receptor, EphA4 / genetics
  • Receptor, EphA4 / metabolism
  • Receptors, Thrombopoietin / genetics
  • Receptors, Thrombopoietin / metabolism*
  • Sialic Acid Binding Ig-like Lectin 3 / genetics
  • Sialic Acid Binding Ig-like Lectin 3 / metabolism
  • Survival Analysis
  • fms-Like Tyrosine Kinase 3 / genetics*

Substances

  • Antigens, CD34
  • Biomarkers, Tumor
  • CD33 protein, human
  • Receptors, Thrombopoietin
  • Sialic Acid Binding Ig-like Lectin 3
  • MPL protein, human
  • Receptor, EphA4
  • fms-Like Tyrosine Kinase 3