THE T(3-5)(Q25.1-Q34) OF MYELODYSPLASTIC-SYNDROME AND ACUTE MYELOID-LEUKEMIA PRODUCES A NOVEL FUSION GENE, NPM-MLF1

Citation
N. Yonedakato et al., THE T(3-5)(Q25.1-Q34) OF MYELODYSPLASTIC-SYNDROME AND ACUTE MYELOID-LEUKEMIA PRODUCES A NOVEL FUSION GENE, NPM-MLF1, Oncogene, 12(2), 1996, pp. 265-275
Citations number
47
Categorie Soggetti
Oncology,Biology,"Cell Biology
Journal title
ISSN journal
09509232
Volume
12
Issue
2
Year of publication
1996
Pages
265 - 275
Database
ISI
SICI code
0950-9232(1996)12:2<265:TTOMAA>2.0.ZU;2-U
Abstract
A t(3;5)(q25.1;q34) chromosomal translocation associated with myelodys plastic syndrome and acute myeloid leukemia (AML) was found to rearran ge 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 identic al 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 functio nal motifs. Normal MLF1 transcripts were expressed in a variety of tis sues, 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 ce lls expressed a 54 kDa NPM-MLF1 protein, but not normal MLF1. Immunost aining experiments indicated that MLF1 is normally located in the cyto plasm, whereas NPM-MLF1 is targeted to the nucleus, with highest level s in the nucleolus. The nuclear/nucleolar localization of NPM-MLF1 mir rors that of NPM, indicating that NPM trafficking signals direct MLF1 to an inappropriate cellular compartment in myeloid leukemia cells.