PRDM16 (1p36) translocations define a distinct entity of myeloid malignancies with poor prognosis but may also occur in lymphoid malignancies

被引：48

作者：

Duhoux, Francois P. ^{[1
]}

Ameye, Genevieve ^{[1
]}

Montano-Almendras, Carmen P. ^{[2
]}

Bahloula, Khadija ^{[1
]}

Mozziconacci, Marie J. ^{[3
]}

Laibe, Sophy ^{[3
]}

Wlodarska, Iwona ^{[4
]}

Michaux, Lucienne ^{[4
]}

Talmant, Pascaline ^{[5
]}

Richebourg, Steven ^{[5
]}

Lippert, Eric ^{[6
]}

Speleman, Frank ^{[7
]}

Herens, Christian ^{[8
]}

Struski, Stephanie ^{[9
]}

Raynaud, Sophie ^{[10
]}

Auger, Nathalie ^{[11
]}

Nadal, Nathalie ^{[12
]}

Rack, Katrina ^{[13
]}

Mugneret, Francine ^{[14
]}

Tigaud, Isabelle ^{[15
]}

Lafage, Marina ^{[16
]}

Taviaux, Sylvie ^{[17
]}

Roche-Lestienne, Catherine ^{[18
]}

Latinne, Dominique ^{[19
]}

Libouton, Jeanne M. ^{[1
]}

Demoulin, Jean-Baptiste ^{[2
]}

Poirel, Helene A. ^{[1
]}

机构：

[1] Catholic Univ Louvain, Ctr Human Genet, Clin Univ St Luc, B-1200 Brussels, Belgium

[2] Catholic Univ Louvain, Duve Inst, B-1200 Brussels, Belgium

[3] Inst J Paoli I Calmettes, Marseilles, France

[4] Katholieke Univ Leuven, Ctr Human Genet, Louvain, Belgium

[5] CHU Nantes, F-44035 Nantes 01, France

[6] CHU, Bordeaux, France

[7] Ghent Univ Hosp, Ctr Med Genet, Ghent, Belgium

[8] CHU, Ctr Human Genet, Liege, Belgium

[9] Hop Purpan, Toulouse, France

[10] CHU, Nice, France

[11] Inst Gustave Roussy, Villejuif, France

[12] CHU Hop Nord, St Etienne, France

[13] Inst Pathol & Genet, Gosselies, Belgium

[14] CHU, Dijon, France

[15] Ctr Hosp Lyon Sud, Lyon, France

[16] CHU Timone, Marseilles, France

[17] Hop Arnaud Villeneuve, Montpellier, France

[18] CHU Lille, F-59037 Lille, France

[19] Catholic Univ Louvain, Dept Immunohaematol, Clin Univ St Luc, B-1200 Brussels, Belgium

来源：

BRITISH JOURNAL OF HAEMATOLOGY | 2012年 / 156卷 / 01期

关键词：

1p36; PRDM16; acute myeloid leukaemia; myelodysplastic syndrome; lymphoid malignancy; RUNX1-PRDM16; FUSION; GENE-EXPRESSION; BONE-MARROW; LEUKEMIA; MEL1; IDENTIFICATION; TRANSCRIPTS; PATIENT; RUNX1; T(1/3)(P36; Q21);

D O I：

10.1111/j.1365-2141.2011.08918.x

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：76 / 88

页数：13

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