A risk of essential thrombocythemia in carriers of constitutional CHEK2 gene mutations

被引：21

作者：

Janiszewska, Hanna ^{[1
]}

Bak, Aneta ^{[1
]}

Pilarska, Maria ^{[1
]}

Heise, Marta ^{[1
]}

Junkiert-Czarnecka, Anna ^{[1
]}

Kuliszkiewicz-Janus, Malgorzata ^{[2
]}

Calbecka, Malgorzata ^{[3
]}

Jazwiec, Bozena ^{[2
]}

Wolowiec, Dariusz ^{[2
]}

Kuliczkowski, Kazimierz ^{[2
]}

Haus, Olga ^{[1
,2
]}

机构：

[1] Nicholas Copernicus Univ, Dept Clin Genet, Coll Med, PL-85094 Bydgoszcz, Poland

[2] Med Univ, Dept Hematol Oncol & Bone Marrow Transplantat, Wroclaw, Poland

[3] Municipal Hosp, Dept Hematol, Torun, Poland

来源：

HAEMATOLOGICA-THE HEMATOLOGY JOURNAL | 2012年 / 97卷 / 03期

关键词：

essential thrombocythemia; congenital CHEK2 mutations; CHRONIC LYMPHOCYTIC-LEUKEMIA; PROSTATE-CANCER RISK; MYELOPROLIFERATIVE NEOPLASMS; CHK2; SUSCEPTIBILITY; VARIANTS; DELETION;

D O I：

10.3324/haematol.2011.049494

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Germline mutations of the CHEK2 gene have been reported in some myeloid and lymphoid malignancies, but their impact on development of essential thrombocythemia has not been studied. In 16 out of 106 (15.1%) consecutive patients, newly diagnosed with essential thrombocythemia, we found one of four analyzed CHEK2 mutations: I157T, 1100delC, IVS2+1G > A or del5395. They were associated with the increased risk of disease (OR=3.8; P=0.002). The median age at ET diagnosis among CHEK2+/JAK2V617F+ patients was seven years lower than that among CHEK2/JAK2V617F+ (52 vs. 59 years; P=0.04), whereas there was no difference in the medians of hematologic parameters between these groups. The results obtained suggest that CHEK2 mutations could potentially contribute to the susceptibility to essential thrombocythemia. The germline inactivation of CHEK2, as it seems, has no direct impact on the development of disease, but it could cause disruption of cell cycle checkpoints and initiate or support the cancerogenic process of essential thrombocythemia at a younger age.

引用

页码：366 / 370

页数：5

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