A systematic description of MLL fusion gene formation.
Rearrangements of the MLL gene involve multiple partners and are implicated in both therapy related acute leukemia [tAL] and infant acute leukemia. For these diseases, recently compiled clinical data confirms an elevated frequency of such breakpoints within a 4 kb tract between exon 11 and a region of structural instability adjacent to exon 12. Linked primarily to cases of tAL, interference with topoisomerase II activity may either contribute to the initial DNA lesion directly or indirectly by, for example, providing a physical block to transcription progression. Alternatively, sites of fragmentation may be mis-repaired, guided by intergenic spliced transcripts of the participating genes. Co-transcription of MLL and potential fusion partners may provide the localization that enhances the probability of gene interaction. An indirect role for the leukemogenic activity of topoisomerase II inhibitors would imply that the negative consequences of their use may be separated from their therapeutic effects.
Department of Radiation Oncology, University of California at Davis, 4501 X Street, Sacramento, CA 95817, United States.
Rebecca L
RL
Wright
Department of Radiation Oncology, University of California at Davis, 4501 X Street, Sacramento, CA 95817, United States. Electronic address: andrew.vaughan@ucdmc.ucdavis.edu.
Andrew T M
AT
Vaughan
D000328:Adult; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000378:metabolism; D004843:Epistasis, Genetic; D005091:Exons; D015973:Gene Expression Regulation, Leukemic; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007223:Infant; D007438:Introns; D015456:Leukemia, Biphenotypic, Acute / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics* / Q000378:metabolism; D016609:Neoplasms, Second Primary / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D059003:Topoisomerase Inhibitors / Q000009:adverse effects; D014178:Translocation, Genetic; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
C497422:KMT2A protein, human; D015514:Oncogene Proteins, Fusion; D059003:Topoisomerase Inhibitors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase; D004250:DNA Topoisomerases, Type II
AICDA; Acute leukemia; MLL; Recombinome; Topoisomerase II; Transcription factory; Translocation