Immunophenotyping with CD135 and CD117 predicts the FLT3, IL-7R and TLX3 gene mutations in childhood T-cell acute leukemia

Blood Cells Mol Dis. 2016 Mar:57:74-80. doi: 10.1016/j.bcmd.2015.12.003. Epub 2015 Dec 2.

Abstract

With the combination of immunophenotyping and molecular tests, it is still a challenge to identify the characteristics of T cell acute lymphoblastic leukemia (T-ALL) associated with distinct outcomes. This study tests the possible correlation of cellular expression of CD135 and CD117 with somatic gene mutations in T-ALL. One hundred sixty-two samples were tested, including 143 at diagnosis, 15 from T-lymphoblastic lymphoma at relapse, and four relapse samples from sequential follow-up of T-ALL. CD135 and CD117 monoclonal antibodies were included in the T-ALL panel of flow cytometry. The percentage of cells positivity and the median fluorescence intensity were correlated with gene mutational status. STIL-TAL1, TLX3, FLT3 and IL7R mutations were tested using standard techniques. STIL-TAL1 was found in 24.8%, TLX3 in 12%, IL7R in 10% and FLT3-ITD in 5% of cases. FLT3 and IL7R mutations were mutually exclusive, as were FLT3-ITD and STIL-TAL1. Associations of CD135(high) (p<0.01), CD117(intermediate/high) (p=0.02) and FLT3-ITD, CD117(low) with IL7R(mutated) (p<0.01) and CD135(high) with TLX3(pos) were observed. We conclude that the addition of CD135 and CD117 to the diagnosis can predict molecular aberrations in T-ALL settings, mainly segregating patients with FLT3-ITD, who would benefit from treatment with inhibitors of tyrosine.

Keywords: CD117; CD135, IL7R, TLX3; FLT3 mutations; T-cell acute lymphoblastic leukemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antibodies, Monoclonal
  • Antineoplastic Agents / therapeutic use
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / immunology
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / immunology
  • Child
  • Child, Preschool
  • Female
  • Gene Expression
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / immunology
  • Humans
  • Immunophenotyping
  • Infant
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / immunology
  • Male
  • Mutation
  • Oncogene Proteins, Fusion / genetics
  • Oncogene Proteins, Fusion / immunology
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / diagnosis
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / immunology
  • Proto-Oncogene Proteins c-kit / genetics*
  • Proto-Oncogene Proteins c-kit / immunology
  • Receptors, Interleukin-7 / genetics*
  • Receptors, Interleukin-7 / immunology
  • Recurrence
  • T-Cell Acute Lymphocytic Leukemia Protein 1
  • Young Adult
  • fms-Like Tyrosine Kinase 3 / genetics*
  • fms-Like Tyrosine Kinase 3 / immunology

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Basic Helix-Loop-Helix Transcription Factors
  • Biomarkers, Tumor
  • Homeodomain Proteins
  • Intracellular Signaling Peptides and Proteins
  • Oncogene Proteins, Fusion
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins
  • Receptors, Interleukin-7
  • STIL protein, human
  • T-Cell Acute Lymphocytic Leukemia Protein 1
  • TLX3 protein, human
  • TAL1 protein, human
  • FLT3 protein, human
  • Proto-Oncogene Proteins c-kit
  • fms-Like Tyrosine Kinase 3