title: Detection of NPM/MLF1 fusion in t(3;5)-positive acute myeloid leukemia and myelodysplasia.
abstract: Balanced translocations are rare in myelodysplasia (MDS) and acute myeloid leukemia (AML) with multilineage dysplasia; however, the t(3;5)(q25;q35) and insertion variant occur in a subset of patients. To evaluate the possible genes involved in this translocation, we studied 6 cases with a t(3;5) by fluorescence in situ hybridization with probes directed against the nucleophosmin (NPM), EVI1, and Ribophorin genes, as well as a newly developed myeloid leukemia factor 1 (MLF1) BAC clone. The histologic spectrum of the cases was variable, ranging from refractory cytopenia with multilineage dysplasia to AML with multilineage dysplasia in the World Health Organization classification. An NPM/MLF1 fusion was identified in 5 of 6 cases, whereas the EVI1 and Ribophorin genes were not involved in any of the cases. The NPM/MLF1-positive cases were predominantly young adult males (median age, 33 years) who responded well to hematopoietic stem cell transplantation. These findings suggest that an NPM/MLF1 fusion is the primary molecular abnormality in t(3;5) MDS and AML with multilineage dysplasia, and also that cases with NPM/MLF1 may be clinically distinct from other MDS-associated disease.
mesh_terms: D000328:Adult; D018797:Cell Cycle Proteins; D002893:Chromosomes, Human, Pair 3; D002895:Chromosomes, Human, Pair 5; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D000090243:Nucleophosmin; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012334:RNA, Neoplasm / Q000032:analysis; D011993:Recombinant Fusion Proteins / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014178:Translocation, Genetic
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C100852:MLF1 protein, human; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D011506:Proteins; D012334:RNA, Neoplasm; D011993:Recombinant Fusion Proteins; D000090243:Nucleophosmin