Molecular Studies on Chromosomal Translocations in Leukemias

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Chromosomal abnormalities such as deletions, translocations and inversions have been identified in various tumors. Recurring and highly consistent chromosomal aberrations often lead to the activation of proto-oncogene products or the creation of tumor-specific fusion proteins, and are usually associated with tumor development and expansion. We have succeeded in identifying several leukemogenic fusion proteins, including AML1-MTG8 and FUS-ERG, using molecular cloning of the breakpoints of the t(8;21) and t(16;21)translocations associated with acute myeloid leukemia. Furthermore, studies of therapy-related secondary leukemias with chromosomal aberrations inv(11), t(2;11), t(16;21) and t(8;22) have led to the isolation of the fusion gene products NUP98-DDX10, NUP98-HOXD13, AML1-MTG16 and MOZ-p300, respectively. Many of these fusion gene products are chimeric transcription factors, and so it seems highly likelythat transcriptional control plays a major role in the etiology of leukemia.