The t(3;5)(q25.1;q34) of myelodysplastic syndrome and acute myeloid leukemia produces a novel fusion gene, NPM-MLF1

Noriko Yoneda-Kato, A. Thomas Look, Mark N. Kirstein, Marcus B. Valentine, Susana C. Raimondi, Kenneth J. Cohen, Andrew J. Carroll, Stephan W. Morris

Research output: Contribution to journalArticlepeer-review

Abstract

A t(3;5)(q25.1;q34) chromosomal translocation associated with myelodysplastic syndrome and acute myeloid leukemia (AML) was found to rearrange part of the nucleophosmin (NPM) gene on chromosome 5 with sequences from a novel gene on chromosome 3. Chimeric transcripts expressed by these cells contain 5' NPM coding sequences fused in-frame to those of the new gene, which we named myelodysplasia/myeloid leukemia factor 1 (MLF1). RNA-based polymerase chain reaction analysis revealed identical NPM-MLF1 mRNA fusions in each of the three t(3;5)-positive cases of AML examined. The predicted MLF1 amino acid sequence lacked homology to previously characterized proteins and did not contain known functional motifs. Normal MLF1 transcripts were expressed in a variety of tissues, most abundantly in testis, ovary, skeletal muscle, heart, kidney and colon. Anti-MLF1 antibodies detected the wild-type 31 kDa protein in K562 and HEL erythroleukemia cell lines, but not in HL-60, U937 or KG-1 myeloid leukemia lines. By contrast, t(3;5)-positive leukemia cells expressed a 54 kDa NPM-MLF1 protein, but not normal MLF1. Immunostaining experiments indicated that MLF1 is normally located in the cytoplasm, whereas NPM-MLF1 is targeted to the nucleus, with highest levels in the nucleolus. The nuclear/nucleolar localization of NPM-MLF1 mirrors that of NPM, indicating that NPM trafficking signals direct MLF1 to an inappropriate cellular compartment in myeloid leukemia cells.

Original languageEnglish (US)
Pages (from-to)265-275
Number of pages11
JournalOncogene
Volume12
Issue number2
StatePublished - 1996

Keywords

  • Acute myeloid leukemia
  • Fusion gene
  • Myelodysplasia-myeloid leukemia factor 1 (MLF1)
  • Nucleophosmin (NPM)
  • t(3;5) chromosomal translocation

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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