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)

Proc Natl Acad Sci U S A. 1999 May 25;96(11):6428-33. doi: 10.1073/pnas.96.11.6428.

Abstract

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.

Publication types

  • Case Reports
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Amino Acid Sequence
  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Base Sequence
  • Child
  • Chromosome Mapping
  • Chromosomes, Human, Pair 11*
  • Chromosomes, Human, Pair 17*
  • Cyclophosphamide / administration & dosage
  • DNA-Binding Proteins / genetics*
  • Drosophila / genetics
  • Female
  • GTP Phosphohydrolases*
  • GTP-Binding Proteins / chemistry
  • GTP-Binding Proteins / genetics*
  • Histone-Lysine N-Methyltransferase
  • Hodgkin Disease / drug therapy*
  • Humans
  • Leukemia, Myeloid / chemically induced*
  • Leukemia, Myeloid / genetics*
  • Male
  • Molecular Sequence Data
  • Myeloid-Lymphoid Leukemia Protein
  • Organ Specificity
  • Prednisone / administration & dosage
  • Procarbazine / administration & dosage
  • Proto-Oncogenes*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Septins
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Transcription Factors*
  • Translocation, Genetic*
  • Vincristine / administration & dosage
  • Zinc Fingers

Substances

  • DNA-Binding Proteins
  • KMT2A protein, human
  • Transcription Factors
  • Myeloid-Lymphoid Leukemia Protein
  • Procarbazine
  • Vincristine
  • Cyclophosphamide
  • Histone-Lysine N-Methyltransferase
  • GTP Phosphohydrolases
  • GTP-Binding Proteins
  • SEPTIN9 protein, human
  • Septins
  • Prednisone

Supplementary concepts

  • COPP protocol

Associated data

  • GENBANK/AF123052