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).
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.
Osaka
M
M
Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
Rowley
J D
JD
Zeleznik-Le
N J
NJ
D000208:Acute Disease; D000595:Amino Acid Sequence; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001483:Base Sequence; D002648:Child; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D002886:Chromosomes, Human, Pair 17; D003520:Cyclophosphamide / Q000008:administration & dosage; D004268:DNA-Binding Proteins / Q000235:genetics*; D004330:Drosophila / Q000235:genetics; D005260:Female; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D011495:Histone-Lysine N-Methyltransferase; D006689:Hodgkin Disease / Q000188:drug therapy*; D006801:Humans; D007951:Leukemia, Myeloid / Q000139:chemically induced* / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D051788:Myeloid-Lymphoid Leukemia Protein; D009928:Organ Specificity; D011241:Prednisone / Q000008:administration & dosage; D011344:Procarbazine / Q000008:administration & dosage; D011519:Proto-Oncogenes; D020133:Reverse Transcriptase Polymerase Chain Reaction; D058112:Septins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors; D014178:Translocation, Genetic; D014750:Vincristine / Q000008:administration & dosage; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011344:Procarbazine; D014750:Vincristine; D003520:Cyclophosphamide; D011495:Histone-Lysine N-Methyltransferase; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; C474315:SEPTIN9 protein, human; D058112:Septins; D011241:Prednisone