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

Summary. 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+/TCRα/β+ 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.