title: Molecular characterization of a t(1;3)(p36;q21) in a patient with MDS. MEL1 is widely expressed in normal tissues, including bone marrow, and it is not overexpressed in the t(1;3) cells.
abstract: Patients with myeloid malignancies and either the 3q21q26 syndrome or t(1;3)(p36;q21) have been reported to share similar clinicopathological features and a common molecular mechanism for leukemogenesis. Overexpression of MDS1/EVI1 (3q26) or MEL1/PRDM16 (1p36), both members of the PR-domain family, has been directly implicated in the malignant transformation of this subset of neoplasias. The breakpoints in both entities are outside the genes, and the 3q21 region, where RPN1 is located, seems to act as an enhancer. MEL1 has been reported to be expressed in leukemia cells with t(1;3) and in the normal uterus and fetal kidney, but neither in bone marrow (BM) nor in other tissues, suggesting that this gene is specific to t(1;3)-positive MDS/AML. We report the molecular characterization of a t(1;3)(p36;q21) in a patient with MDS (RAEB-2). In contrast to previous studies, we demonstrate that MEL1, the PR-containing form, and MEL1S, the PR-lacking form, are widely expressed in normal tissues, including BM. The clinicopathological features and the breakpoint on 1p36 are different from cases previously described, and MEL1 is not overexpressed, suggesting a heterogeneity in myeloid neoplasias with t(1;3).
authors.affiliation: Department of Genetics, University of Navarra, C/Irunlarrea s/n, Pamplona 31008, Spain.
authors.forename: Idoya
authors.initials: I
authors.lastname: Lahortiga
authors.forename: Xabier
authors.initials: X
authors.lastname: Agirre
authors.forename: Elena
authors.initials: E
authors.lastname: Belloni
authors.forename: Iria
authors.initials: I
authors.lastname: Vázquez
authors.forename: María J
authors.initials: MJ
authors.lastname: Larrayoz
authors.forename: Patrizia
authors.initials: P
authors.lastname: Gasparini
authors.forename: Francesco
authors.initials: F
authors.lastname: Lo Coco
authors.forename: Pier Giuseppe
authors.initials: PG
authors.lastname: Pelicci
authors.forename: María J
authors.initials: MJ
authors.lastname: Calasanz
authors.forename: María D
authors.initials: MD
authors.lastname: Odero
mesh_terms: D000368:Aged; D001853:Bone Marrow / Q000378:metabolism; D002878:Chromosomes, Human, Pair 1; D002893:Chromosomes, Human, Pair 3; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D015514:Oncogene Proteins, Fusion; D011993:Recombinant Fusion Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: D004268:DNA-Binding Proteins; C098704:MDS1-EVI1 fusion protein, human; D015514:Oncogene Proteins, Fusion; C416371:PRDM16 protein, human; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors