In aggressive forms of mastocytosis, TET2 loss cooperates with c-KITD816V to transform mast cells

被引：84

作者：

Soucie, Erinn ^{[1
]}

Hanssens, Katia ^{[1
]}

Mercher, Thomas ^{[2
]}

Georgin-Lavialle, Sophie ^{[3
,4
,5
]}

Damaj, Gandhi ^{[6
]}

Livideanu, Cristina ^{[7
]}

Chandesris, Maria Olivia ^{[3
,8
]}

Acin, Yolene ^{[9
]}

Letard, Sebastien ^{[1
]}

de Sepulveda, Paulo ^{[1
]}

Hermine, Olivier ^{[3
,4
,8
]}

Bernard, Olivier A. ^{[2
]}

Dubreuil, Patrice ^{[1
]}

机构：

[1] Univ Mediterranee, INSERM, Inst J Paoli I Calmettes, Ctr Rech Cancerol Marseille,U1068,Ctr Reference M, F-13273 Marseille 09, France

[2] Univ Paris 11, Inst Gustave Roussy, INSERM, U985, Villejuif, France

[3] Univ Paris 05, Hop Necker Enfants Malad, Ctr Reference Mastocytoses, Paris, France

[4] CNRS, Unite Mixte Rech 8147, Paris, France

[5] Hop Europeen Georges Pompidou, Serv Med Interne, Paris, France

[6] Ctr Hosp Univ, Dept Hematol, Amiens, France

[7] Hop Larrey, Toulouse, France

[8] Hop Necker Enfants Malad, Serv Hematol Adulte, Paris, France

[9] AB Sci, Paris, France

来源：

BLOOD | 2012年 / 120卷 / 24期

关键词：

PEDIATRIC MASTOCYTOSIS; SELF-RENEWAL; C-KIT; MUTATIONS; DIFFERENTIATION;

D O I：

10.1182/blood-2011-12-397588

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Although a role for oncogenic KIT in driving mast cell disease is clear, the mechanisms driving the multiple phenotypic and clinical manifestations of this disorder are not well elucidated. We now show, using a large cohort of mastocytosis patients, including an almost equal number of aggressive and nonaggressive cases of systemic mastocytosis, that in contrast to the oncogenic KITD816V, TET2 mutation statistically associates with aggressive forms of the disease. By infecting primary murine bone marrow-derived mast cells with KITD816V, we also observe a significant and competitive growth advantage for KITD816V in Tet2-nullizygous compared with wild-type cells. TET2-deficient cells display in-creased proliferation and can survive in the absence of cytokines. Taken together, these data demonstrate a oncogenic cooperation in mast cells and reveal TET2 mutation as a potential marker to diagnose and predict severe forms of mastocytosis. (Blood. 2012;120(24):4846-4849)

引用

页码：4846 / 4849

页数：4

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