Identification of an ETV6-ABL2 fusion transcript in combination with an ETV6 point mutation in a T-cell acute lymphoblastic leukaemia cell line

Br J Haematol. 2002 Nov;119(2):454-8. doi: 10.1046/j.1365-2141.2002.03850.x.

Abstract

ETV6, a member of the Ets family of transcription factors, is frequently rearranged to various translocation partners in human leukaemias. We previously described a CD3+/TCRalpha/beta+ mature T-cell acute lymphoblastic leukaemia (T-ALL) cell line, MT-ALL, carrying a t(1;10;12)(q25; p13;p13) with cytokine-inducible lineage switch into the myeloid lineage. Using reverse transcription polymerase chain reaction with primers complementary to ETV6 and ABL2, two ETV6-ABL2 fusion transcripts were identified in MT-ALL which resulted from alternative splicing of an ABL2 exon. The fusion transcripts code for putative ETV6-ABL2 fusion proteins containing the pointed domain of ETV6 and almost the complete ABL2 protein, including the SH2, SH3 domains and the protein tyrosine kinase domain (PTK). Identical ETV6-ABL2 fusion transcripts have been reported in an acute myeloid leukaemia (AML) M3 cell line, carrying both a t(15;17)(q22;q21) and a t(1;12)(q25;p13) with unusual inducible differentiation to eosinophils, and in a patient with AML-M4eo. Interestingly, the non-rearranged allele of ETV6 in the MT-ALL cell line carries an arginine to histidine (R399H) mutation which affects a conserved amino acid in the ets DNA binding domain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Artificial Gene Fusion
  • Base Sequence
  • DNA-Binding Proteins / genetics*
  • ETS Translocation Variant 6 Protein
  • Humans
  • Leukemia-Lymphoma, Adult T-Cell / genetics*
  • Mice
  • Mice, SCID
  • Molecular Sequence Data
  • Oncogene Proteins, Fusion / genetics*
  • Point Mutation*
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-ets
  • Repressor Proteins / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • DNA-Binding Proteins
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins c-ets
  • Repressor Proteins
  • TEL-ABL fusion protein, human
  • Protein-Tyrosine Kinases