title: PRDM16 (1p36) translocations define a distinct entity of myeloid malignancies with poor prognosis but may also occur in lymphoid malignancies.
abstract: The PRDM16 (1p36) gene is rearranged in acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) with t(1;3)(p36;q21), sharing characteristics with AML and MDS with MECOM (3q26.2) translocations. We used fluorescence in situ hybridization to study 39 haematological malignancies with translocations involving PRDM16 to assess the precise breakpoint on 1p36 and the identity of the partner locus. Reverse-transcription polymerase chain reaction (PCR) was performed in selected cases in order to confirm the partner locus. PRDM16 expression studies were performed on bone marrow samples of patients, normal controls and CD34(+) cells using TaqMan real-time quantitative PCR. PRDM16 was rearranged with the RPN1 (3q21) locus in 30 cases and with other loci in nine cases. The diagnosis was AML or MDS in most cases, except for two cases of lymphoid proliferation. We identified novel translocation partners of PRDM16, including the transcription factors ETV6 and IKZF1. Translocations involving PRDM16 lead to its overexpression irrespective of the consequence of the rearrangement (fusion gene or promoter swap). Survival data suggest that patients with AML/MDS and PRDM16 translocations have a poor prognosis despite a simple karyotype and a median age of 65 years. There seems to be an over-representation of late-onset therapy-related myeloid malignancies.
authors: Centre for Human Genetics, Cliniques universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium.
authors: Francois P
authors: FP
authors: Duhoux
authors: Geneviève
authors: G
authors: Ameye
authors: Carmen P
authors: CP
authors: Montano-Almendras
authors: Khadija
authors: K
authors: Bahloula
authors: Marie J
authors: MJ
authors: Mozziconacci
authors: Sophy
authors: S
authors: Laibe
authors: Iwona
authors: I
authors: Wlodarska
authors: Lucienne
authors: L
authors: Michaux
authors: Pascaline
authors: P
authors: Talmant
authors: Steven
authors: S
authors: Richebourg
authors: Eric
authors: E
authors: Lippert
authors: Frank
authors: F
authors: Speleman
authors: Christian
authors: C
authors: Herens
authors: Stéphanie
authors: S
authors: Struski
authors: Sophie
authors: S
authors: Raynaud
authors: Nathalie
authors: N
authors: Auger
authors: Nathalie
authors: N
authors: Nadal
authors: Katrina
authors: K
authors: Rack
authors: Francine
authors: F
authors: Mugneret
authors: Isabelle
authors: I
authors: Tigaud
authors: Marina
authors: M
authors: Lafage
authors: Sylvie
authors: S
authors: Taviaux
authors: Catherine
authors: C
authors: Roche-Lestienne
authors: Dominique
authors: D
authors: Latinne
authors: Jeanne M
authors: JM
authors: Libouton
authors: Jean-Baptiste
authors: JB
authors: Demoulin
authors: Hélène A
authors: HA
authors: Poirel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002871:Chromosome Banding; D056905:Chromosome Breakpoints; D002878:Chromosomes, Human, Pair 1; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D023061:Gene Order; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D008223:Lymphoma / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics; D011379:Prognosis; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; D015514:Oncogene Proteins, Fusion; C416371:PRDM16 protein, human; D014157:Transcription Factors