Myelodysplasia and leukemia of Fanconi anemia are associated with a specific pattern of genomic abnormalities that includes cryptic RUNX1/AML1 lesions

被引：139

作者：

Quentin, Samuel ^{[1
,2
,3
]}

Cuccuini, Wendy ^{[1
,2
,3
]}

Ceccaldi, Raphael ^{[1
,2
,3
]}

Nibourel, Olivier ^{[4
,5
,6
]}

Pondarre, Corinne ^{[7
,8
]}

Pages, Marie-Pierre ^{[9
]}

Vasquez, Nadia ^{[1
,2
,3
,10
]}

d'Enghien, Catherine Dubois ^{[11
]}

Larghero, Jerome ^{[12
]}

de Latour, Regis Peffault ^{[10
]}

Rocha, Vanderson ^{[10
]}

Dalle, Jean-Hugues ^{[10
,13
,14
]}

Schneider, Pascale ^{[15
]}

Michallet, Mauricette ^{[9
]}

Michel, Gerard ^{[16
]}

Baruchel, Andre ^{[10
,13
,14
]}

Sigaux, Francois ^{[1
,2
,3
]}

Gluckman, Eliane ^{[10
]}

Leblanc, Thierry ^{[10
,13
,14
]}

Stoppa-Lyonnet, Dominique ^{[11
]}

Preudhomme, Claude ^{[4
,5
,6
]}

Socie, Gerard ^{[10
]}

Soulier, Jean ^{[1
,2
,3
,10
]}

机构：

[1] Univ Paris 07, St Louis Hosp, AP HP, Hematol Lab,Team Genome & Canc, F-75010 Paris, France

[2] St Louis Hosp, INSERM, U944, Paris, France

[3] Univ Paris Diderot, Inst Univ Hematol, Paris, France

[4] Ctr Hosp Reg Univ Lille, Hematol Lab, Lille, France

[5] INSERM, U837, Team 3, F-59045 Lille, France

[6] Univ Lille Nord France, Lille, France

[7] Inst Hematol & Oncol Pediat, Lyon, France

[8] Univ Lyon 1, F-69365 Lyon, France

[9] Lyon Sud Hosp, Dept Hematol, Lyon, France

[10] French Natl Reference Ctr Constitut Bone Marrow F, Paris, France

[11] Inst Curie, Oncogenet Lab, Paris, France

[12] St Louis Hosp, Cell Therapy Unit, Paris, France

[13] Robert Debre Hosp, AP HP, Pediat Hematol Dept, Paris, France

[14] St Louis Hosp, AP HP, Pediat Hematol Dept, Paris, France

[15] Charles Nicolle Hosp, Dept Pediat Oncol, Rouen, France

[16] La Timone Hosp, Dept Pediat Hematol, Marseille, France

来源：

BLOOD | 2011年 / 117卷 / 15期

关键词：

ACUTE MYELOID-LEUKEMIA; METHYLTRANSFERASE GENE EZH2; CYTOGENETIC ABNORMALITIES; PROGNOSTIC-SIGNIFICANCE; EX-VIVO; MUTATIONS; CELLS; RISK; OVEREXPRESSION; TRANSLOCATION;

D O I：

10.1182/blood-2010-09-308726

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Fanconi anemia (FA) is a genetic condition associated with bone marrow (BM) failure, myelodysplasia (MDS), and acute myeloid leukemia (AML). We studied 57 FA patients with hypoplastic or aplastic anemia (n = 20), MDS (n = 18), AML (n = 11), or no BM abnormality (n = 8). BM samples were analyzed by karyotype, high-density DNA arrays with respect to paired fibroblasts, and by selected oncogene sequencing. A specific pattern of chromosomal abnormalities was found in MDS/AML, which included 1q+ (44.8%), 3q+ (41.4%), -7/7q (17.2%), and 11q- (13.8%). Moreover, cryptic RUNX1/AML1 lesions (translocations, deletions, or mutations) were observed for the first time in FA (20.7%). Rare mutations of NRAS, FLT3-ITD, MLL-PTD, ERG amplification, and ZFP36L2-PRDM16 translocation, but no TP53, TET2, CBL, NPM1, and CEBP alpha mutations were found. Frequent homozygosity regions were related not to somatic copy-neutral loss of heterozygosity but to consanguinity, suggesting that homologous recombination is not a common progression mechanism in FA. Importantly, the RUNX1 and other chromosomal/genomic lesions were found at the MDS/AML stages, except for 1q+, which was found at all stages. These data have implications for staging and therapeutic managing in FA patients, and also to analyze the mechanisms of clonal evolution and oncogenesis in a background of genomic instability and BM failure. (Blood. 2011; 117(15):e161-e170)

引用

页码：E161 / E170

页数：10

共 51 条

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