Open AccessIdentification of a novel fusion gene in a pre‐B acute lymphoblastic leukemia with t(1;19)(q23;p13)
Author(s) -
Yuki Yasuhiro,
Imoto Issei,
Imaizumi Masue,
Hibi Shigeyoshi,
Kaneko Yasuhiko,
Amagasa Teruo,
Inazawa Johji
Publication year - 2004
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2004.tb03240.x
Subject(s) - fusion gene , biology , intron , fusion transcript , cell fusion , chromosomal translocation , gene , oncogene proteins , hela , cancer research , genetics , cell culture , regulation of gene expression
The most common nonrandom translocation found among childhood pre‐B acute lymphoblastic leukemias (ALL) is t(1;19)(q23;p13), which frequently results in fusion of E2A with PBX1 . However, rare cases of childhood ALL and various other hematological diseases with t(1;19) lack the E2A‐PBX1 fusion. Analyzing a cell line with pre‐B‐cell phenotype, TS‐2, that carries t(1;19)(q23;p13) but lacks the E2A‐PBX1 fusion, we successfully cloned the breakpoints, which fell within introns of MEF2D and DAZAP1 . Both chimeric transcripts, MEF2D‐DAZAP1 and DAZAP1‐MEF2D , whose sequences indicated in‐frame fusions between MEF2D and DAZAP1, were expressed in TS‐2 cells and in bone‐marrow cells of the patient from whom the TS‐2 was established. MEF2D‐DAZAP1 and DAZAP1‐MEF2D proteins were both located in the nucleus, and MEF2D‐DAZAP1 was able to form dimers with MEF2D and HDAC4. In addition, exogenous expression of MEF2D‐DAZAP1 and DAZAP1‐MEF2D promoted the growth of HeLa cells. Given the frequency of t(1;19) without the E2A‐PBX1 fusion in hematological malignancies, we suggest that MEF2D/DAZAP1 rearrangements might be involved in the pathogenesis of those diseases.