Identification of a novel fusion gene, TTL, fused to ETV6 in acute lymphoblastic leukemia with t(12;13)(p13;q14), and its implication in leukemogenesis

Leukemia
Y QiaoH Hirai

Abstract

ETS variant gene 6 (ETV6)/translocation, ETS, leukemia (TEL)-involving chromosomal translocations are frequently observed in various hematologic neoplasms. We describe here a novel ETV6-involving translocation, t(12;13)(p13;q14), found in the case of acute lymphoblastic leukemia, in which ETV6 fused with a previously unknown gene, named Twelve-thirteen Translocation Leukemia gene (TTL), at 13q14. TTL was weakly but ubiquitously expressed in normal human tissues as detected by reverse transcribed-PCR. Three TTL splicing forms were identified, TTL-T from a human testis cDNA library, with an open-reading frame of 402 bp encoding 133 amino acids (aa), and TTL-B1 and -B2 from a human brain cDNA library. These proteins have no homology to known proteins. In leukemic cells from the patient, both reciprocal fusion transcripts, ETV6/TTL and TTL/ETV6, were expressed. The predominant fusion transcript, TTL/ETV6-1, encodes a predicted 530 aa fusion protein containing 89 aa of the N-terminal TTL fusing to the helix-loop-helix domain and ETS-binding domain of ETV6. Although the function of TTL is yet to be elucidated, our findings will provide another insight into the molecular pathogenesis of leukemia having ETV6-involving translocations.

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Citations

Feb 22, 2005·Cancer Genetics and Cytogenetics·L VieiraM G Boavida
Apr 14, 2005·Seminars in Cancer Biology·Stefan K Bohlander
May 15, 2012·Leukemia Research·Etienne De BraekeleerMarc De Braekeleer
Nov 19, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Ayalew Tefferi
May 8, 2007·International Journal of Hematology·Kazuhiro Morishita
Jul 23, 2019·Critical Reviews in Biotechnology·Ayodeji AmobonyeSanthosh Pillai

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