Genetic profile of T-cell acute lymphoblastic leukemias with MYC translocations

Blood. 2014 Dec 4;124(24):3577-82. doi: 10.1182/blood-2014-06-578856. Epub 2014 Sep 30.

Abstract

MYC translocations represent a genetic subtype of T-lineage acute lymphoblastic leukemia (T-ALL), which occurs at an incidence of ∼6%, assessed within a cohort of 196 T-ALL patients (64 adults and 132 children). The translocations were of 2 types; those rearranged with the T-cell receptor loci and those with other partners. MYC translocations were significantly associated with the TAL/LMO subtype of T-ALL (P = .018) and trisomies 6 (P < .001) and 7 (P < .001). Within the TAL/LMO subtype, gene expression profiling identified 148 differentially expressed genes between patients with and without MYC translocations; specifically, 77 were upregulated and 71 downregulated in those with MYC translocations. The poor prognostic marker, CD44, was among the upregulated genes. MYC translocations occurred as secondary abnormalities, present in subclones in one-half of the cases. Longitudinal studies indicated an association with induction failure and relapse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Chromosomes, Human, Pair 6 / genetics
  • Chromosomes, Human, Pair 6 / metabolism
  • Chromosomes, Human, Pair 7 / genetics
  • Chromosomes, Human, Pair 7 / metabolism
  • Disease-Free Survival
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Hyaluronan Receptors / biosynthesis
  • Hyaluronan Receptors / genetics
  • Male
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / metabolism*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Proto-Oncogene Proteins c-myc / genetics*
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Survival Rate
  • Translocation, Genetic*
  • Trisomy / genetics

Substances

  • CD44 protein, human
  • Hyaluronan Receptors
  • MYC protein, human
  • Proto-Oncogene Proteins c-myc

Supplementary concepts

  • Chromosome 6, trisomy 6p
  • Chromosome 7, trisomy 7p