Prognostic significance of molecular-cytogenetic abnormalities in pediatric T-ALL is not explained by immunophenotypic differences

Leukemia. 2008 Jan;22(1):124-31. doi: 10.1038/sj.leu.2404957. Epub 2007 Oct 11.

Abstract

Pediatric T-cell acute lymphoblastic leukemia (T-ALL) is characterized by chromosomal rearrangements possibly enforcing arrest at specific development stages. We studied the relationship between molecular-cytogenetic abnormalities and T-cell development stage to investigate whether arrest at specific stages can explain the prognostic significance of specific abnormalities. We extensively studied 72 pediatric T-ALL cases for genetic abnormalities and expression of transcription factors, NOTCH1 mutations and expression of specific CD markers. HOX11 cases were CD1 positive consistent with a cortical stage, but as 4/5 cases lacked cytoplasmatic-beta expression, developmental arrest may precede beta-selection. HOX11L2 was especially confined to immature and pre-AB developmental stages, but 3/17 HOX11L2 mature cases were restricted to the gammadelta-lineage. TAL1 rearrangements were restricted to the alphabeta-lineage with most cases being TCR-alphabeta positive. NOTCH1 mutations were present in all molecular-cytogenetic subgroups without restriction to a specific developmental stage. CALM-AF10 was associated with early relapse. TAL1 or HOX11L2 rearrangements were associated with trends to good and poor outcomes, respectively. Also cases with high vs low TAL1 expression levels demonstrated a trend toward good outcome. Most cases with lower TAL1 levels were HOX11L2 or CALM-AF10 positive. NOTCH1 mutations did not predict for outcome. Classification into T-cell developmental subgroups was not predictive for outcome.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Cell Lineage
  • Child
  • Female
  • Gene Rearrangement / genetics*
  • Homeodomain Proteins / genetics
  • Humans
  • Immunophenotyping
  • In Situ Hybridization, Fluorescence
  • Leukemia-Lymphoma, Adult T-Cell / diagnosis
  • Leukemia-Lymphoma, Adult T-Cell / genetics*
  • Leukemia-Lymphoma, Adult T-Cell / metabolism
  • Male
  • Mutation / genetics
  • Neoplasm Recurrence, Local / genetics*
  • Oncogene Proteins, Fusion / genetics
  • Prognosis
  • Proto-Oncogene Proteins / genetics
  • RNA, Messenger / genetics
  • RNA, Neoplasm / genetics
  • Receptor, Notch1 / genetics*
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, gamma-delta / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Cell Acute Lymphocytic Leukemia Protein 1

Substances

  • AF10-CALM fusion protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • Homeodomain Proteins
  • NOTCH1 protein, human
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • Receptor, Notch1
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta
  • T-Cell Acute Lymphocytic Leukemia Protein 1
  • TLX3 protein, human
  • TAL1 protein, human