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MSF (MLL Septin-Like Fusion), a Fusion Partner Gene of MLL, in a Therapy-Related Acute Myeloid Leukemia with a t(11;17)(q23;q25)
Mitsuhiko Osaka, Janet D. Rowley and Nancy J. Zeleznik-Le
Proceedings of the National Academy of Sciences of the United States of America
Vol. 96, No. 11 (May 25, 1999), pp. 6428-6433
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/47887
Page Count: 6
You can always find the topics here!Topics: Leukemia, Complementary DNA, Genes, Proteins, DNA, Exons, Polymerase chain reaction, Reverse transcriptase polymerase chain reaction, Myeloid leukemia, Chromosome translocation
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MLL (ALL1, Htrx, HRX), which is located on chromosome band 11q23, frequently is rearranged in patients with therapy-related acute myeloid leukemia who previously were treated with DNA topoisomerase II inhibitors. In this study, we have identified a fusion partner of MLL in a 10-year-old female who developed therapy-related acute myeloid leukemia 17 months after treatment for Hodgkin's disease. Leukemia cells of this patient had a t(11;17)(q23;q25), which involved MLL as demonstrated by Southern blot analysis. The partner gene was cloned from cDNA of the leukemia cells by use of a combination of adapter reverse transcriptase-PCR, rapid amplification of 5′ cDNA ends, and BLAST database analysis to identify expressed sequence tags. The full-length cDNA of 2.8 kb was found to be an additional member of the septin family, therefore it was named MSF (MLL septin-like fusion). Members of the septin family conserve the GTP binding domain, localize in the cytoplasm, and interact with cytoskeletal filaments. A major 4-kb transcript of MSF was expressed ubiquitously; a 1.7-kb transcript was found in most tissues. An additional 3-kb transcript was found only in hematopoietic tissues. By amplification with MLL exon 5 forward primer and reverse primers in MSF, the appropriately sized products were obtained. MSF is highly homologous to hCDCrel-1, which is a partner gene of MLL in leukemias with a t(11;22)(q23;q11.2). Further analysis of MSF may help to delineate the function of MLL partner genes in leukemia, particularly in therapy-related leukemia.
Proceedings of the National Academy of Sciences of the United States of America © 1999 National Academy of Sciences