Identification of a novel fusion gene in a pre-B acute lymphoblastic leukemia with t(1;19)(q23;p13) - PubMed (original) (raw)
Identification of a novel fusion gene in a pre-B acute lymphoblastic leukemia with t(1;19)(q23;p13)
Yasuhiro Yuki et al. Cancer Sci. 2004 Jun.
Abstract
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.
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References
- Greaves MF, Wiemels J. Origins of chromosome translocations in childhood leukaemia. Nat Rev Cancer 2003; 3: 639–49. - PubMed
- Nourse J, Mellentin JD, Galili N, Wilkinson J, Stanbridge E, Smith SD, Cleary ML. Chromosomal translocation t(l;19) results in synthesis of a homeobox fusion mRNA that codes for a potential chimeric transcription factor. Cell 1990; 60: 535–45. - PubMed
- Hunger SP, Galili N, Carroll AJ, Crist WM, Link MP, Cleary ML. The t(l;19)(q23;p13) results in consistent fusion of E2A and PBX1 coding sequences in acute lymphoblastic leukemias. Blood 1991; 77: 687–93. - PubMed
- Izraeli S, Janssen JWG, Haas OA, Harbott J, Brok‐Simoni F, Walther JU, Kovar H, Henn T, Ludwig WD, Reiter A, Rechavi G, Bartram CR, Gadner H, Lion T. Detection and clinical relevance of genetic abnormalities in pediatric acute lymphoblastic leukemia: a comparison between cytogenetic and polymerase chain reaction analyses. Leukemia 1993; 7: 671–8. - PubMed
- Troussard X, Rimokh R, Valensi F, Leboeuf D, Fenneteau O, Guitard AM, Manel AM, Schillinger F, Leglise C, Brizard A, Gardais J, Lessard M, Flandrin G, Macintyre E. Heterogeneity of t(1;19)(q23;p13) acute leukemias. BrJ Haematol 1995; 89: 516–26. - PubMed
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