Detection of NPM/ MLF1 fusion in t(3;5)-positive acute myeloid leukemia and myelodysplasia

• Published in: Human pathology 2003-08, Vol.34 (8), p.809-813
• Main Authors: Arber, Daniel A, Chang, Karen L, Lyda, Mark H, Bedell, Victoria, Spielberger, Ricardo, Slovak, Marilyn L
• Format: Article
• Language: English
• Subjects: acute myeloid leukemia; Adult; Biological and medical sciences; Bone marrow; Chromosomes, Human, Pair 3; Chromosomes, Human, Pair 5; Cloning; Cloning, Molecular; cytogenetics; Deoxyribonucleic acid; Disease; DNA; Hematologic and hematopoietic diseases; Humans; In Situ Hybridization, Fluorescence; Leukemia; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - metabolism; Leukemia, Myeloid, Acute - pathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Middle Aged; MLF1; myelodysplasia; Myelodysplastic Syndromes - genetics; Myelodysplastic Syndromes - metabolism; Myelodysplastic Syndromes - pathology; NPM; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Proteins - genetics; Proteins - metabolism; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Neoplasm - analysis; Stem cells; Studies; Translocation, Genetic; Young adults
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/S0046-8177(03)00251-X

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.