Identification of a novel fusion gene in a pre-B acute lymphoblastic leukemia with t(1;19)(q23;p13).
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.
Yuki
Yasuhiro
Y
Department of Molecular Cytogenetics, Medical Research Institute, Graduate School, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan.
Imoto
Issei
I
Imaizumi
Masue
M
Hibi
Shigeyoshi
S
Kaneko
Yasuhiko
Y
Amagasa
Teruo
T
Inazawa
Johji
J
D002675:Child, Preschool; D002878:Chromosomes, Human, Pair 1; D002888:Chromosomes, Human, Pair 19; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; D018006:Myogenic Regulatory Factors; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic
C412481:DAZAP1 protein, human; D004268:DNA-Binding Proteins; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; C578043:MEF2D protein, human; D018006:Myogenic Regulatory Factors; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors