Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2110491 | Cancer Genetics | 2011 | 6 Pages |
Abstract
Chromosomal rearrangements of the MLL gene are uncommon in myelodysplastic syndromes (MDSs), and few studies of their molecular structures and oncogenic mechanisms exist. Here, we present a case of de novo MDS with a normal karyotype at initial diagnosis and a mild clinical course. Five years after the initial diagnosis, investigators identified a complex rearrangement of the MLL gene without progression to acute leukemia. The 5â² part of the MLL gene is fused out of frame with the LOC100131626 gene, and the 3â² part of the MLL gene out of frame with the TCF12 gene. Rapid amplification of complementary DNA 3â² ends yielded two main fusion transcripts, which is in concordance with the two described isoforms of the LOC100131626 gene. For both isoform-fusion transcripts, the open reading frame terminates shortly after the breakpoint that is predicted to form two de facto truncated MLL proteins and disrupts the open reading frame of the LOC100131626, TCF12, and UBE4A genes. Neither dimerization nor a transcriptional activation domain, each of which is causally linked to MLL protein-mediated transformation, is present. This and other unusual MLL rearrangements probably represent a subclass of MLL gene abnormalities that have intrinsically no ability or only a weak ability to transform hematopoeitic cells and are identified only in the context of other hematopoetic malignancies.
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Authors
Claus Meyer, Eric Kowarz, Sze-Fai Yip, Thomas Shek-Kong Wan, Tai-Kwong Chan, Theo Dingermann, Li-Chong Chan, Rolf Marschalek,