title: Breakpoints at 1p36.3 in three MDS/AML(M4) patients with t(1;3)(p36;q21) occur in the first intron and in the 5' region of MEL1.
abstract: The recurrent translocation t(1;3)(p36;q21) is associated with myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML) characterized by trilineage dysplasia, especially dysmegakaryopoiesis and a poor prognosis. Recently, the two genes involved in this translocation have been identified: the MEL1 gene at 1p36.3, and the RPN1 gene at 3q21. The breakpoint in RPN1 is centromeric to the breakpoint cluster region of the inv(3) abnormality. Because the MEL1 transcript is detected only in leukemic cells with t(1;3)(p36;q21), ectopic expression of MEL1 driven by RPN1 at 3q21 is thought to contribute to the pathogenesis of t(1;3)(p36;q21) leukemia. However, the precise breakpoint in the patients has not yet been identified. With fluorescence in situ hybridization analysis by use of BAC/PAC probes, we identified the breakpoint at 1p36.3 in three MDS/AML patients with t(1;3)(p36;q21): within the first intron of the MEL1 gene (one patient) or within a 29-kb region located in the 5' region of MEL1 (two other patients). We detected several sizes of MEL1 transcript in two patients including the first patient, although we have not yet clarified whether MEL1 transcripts were different among the patients and whether a truncated MEL1 transcript was expressed in the first patient. This patient showed an unusual clinical profile, repeating progression to overt leukemia and conversion to MDS three times during the 29-month survival period, which might be related to a different molecular mechanism in this patient.
authors.affiliation: Division of Molecular Cytogenetics, Department of Clinical Pathology, Research Institute of International Medical Center of Japan, Tokyo, Japan.
authors.forename: Phan Thi
authors.initials: PT
authors.lastname: Xinh
authors.forename: Nguyen Khanh
authors.initials: NK
authors.lastname: Tri
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Nagao
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakazato
authors.forename: Fumitoshi
authors.initials: F
authors.lastname: Taketazu
authors.forename: Shin
authors.initials: S
authors.lastname: Fujisawa
authors.forename: Fumiharu
authors.initials: F
authors.lastname: Yagasaki
authors.forename: Ying Zhang
authors.initials: YZ
authors.lastname: Chen
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Toyoda
authors.forename: Masahira
authors.initials: M
authors.lastname: Hattori
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Sakaki
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tokunaga
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sato
mesh_terms: D024506:5' Flanking Region / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D002352:Carrier Proteins / Q000235:genetics*; D019457:Chromosome Breakage / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D004268:DNA-Binding Proteins; D005260:Female; D006801:Humans; D007438:Introns / Q000235:genetics*; D015479:Leukemia, Myelomonocytic, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D014157:Transcription Factors
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C416371:PRDM16 protein, human; D014157:Transcription Factors