Clonal analysis of NRAS activating mutations in KIT-D816V systemic mastocytosis

被引：73

作者：

Wilson, Todd M. ^{[1
]}

Maric, Irina ^{[2
]}

Simakova, Olga ^{[2
]}

Bai, Yun

Chan, Eunice Ching

Olivares, Nicolas ^{[2
]}

Carter, Melody

Maric, Dragan ^{[3
]}

Robyn, Jamie ^{[4
]}

Metcalfe, Dean D.

机构：

[1] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA

[2] Ctr Clin, Dept Lab Med, Bethesda, MD USA

[3] Natl Inst Neurol Disorders & Stroke, Flow Cytometry Core Facil, NIH, Bethesda, MD USA

[4] Dept Vet Affairs, Springfield, OH USA

来源：

HAEMATOLOGICA-THE HEMATOLOGY JOURNAL | 2011年 / 96卷 / 03期

关键词：

systemic mastocytosis; activating mutations; NRAS KIT; ACUTE MYELOID-LEUKEMIA; GENE-MUTATIONS; RAS MUTATIONS; MAST-CELLS; PHASE-II; T-CELLS; C-KIT; DASATINIB; KITD816V; DISORDER;

D O I：

10.3324/haematol.2010.031690

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Cooperating genetic events are likely to contribute to the phenotypic diversity of KIT-D816V systemic mastocytosis. In this study, 44 patients with KIT-D816V systemic mastocytosis were evaluated for coexisting NRAS, KRAS, HRAS or MRAS mutations. Activating NRAS mutations were identified in 2 of 8 patients with advanced disease. NRAS mutations were not found in patients with indolent systemic mastocytosis. To better understand the clonal evolution of mastocytosis, we evaluated the cell compartments impacted by the NRAS and KIT mutations. Clonal mast cells harbored both mutations. KIT-D816V was not detected in bone marrow CD34(+) progenitors, whereas the NRAS mutation was present. These findings suggest that NRAS mutations may have the potential to precede KIT-D816V in clonal development. Unlike other mature lineages, mast cell survival is dependent on KIT and the presence of these two activating mutations may have a greater impact on the expansion of this cell compartment and in resultant disease severity.

引用

页码：459 / 463

页数：5

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