title: A risk of essential thrombocythemia in carriers of constitutional CHEK2 gene mutations.
abstract: 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.
authors: Department of Clinical Genetics, Collegium Medicum, Nicolaus Copernicus University, M. Sklodowska-Curie 9, 85-094 Bydgoszcz, Poland. hannaj@cm.umk.pl
authors: Hanna
authors: H
authors: Janiszewska
authors: Aneta
authors: A
authors: Bak
authors: Maria
authors: M
authors: Pilarska
authors: Marta
authors: M
authors: Heise
authors: Anna
authors: A
authors: Junkiert-Czarnecka
authors: Małgorzata
authors: M
authors: Kuliszkiewicz-Janus
authors: Małgorzata
authors: M
authors: Całbecka
authors: Bozena
authors: B
authors: Jaźwiec
authors: Dariusz
authors: D
authors: Wołowiec
authors: Kazimierz
authors: K
authors: Kuliczkowski
authors: Olga
authors: O
authors: Haus
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D064447:Checkpoint Kinase 2; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012306:Risk; D013920:Thrombocythemia, Essential / Q000235:genetics*; D055815:Young Adult
chemical_list: D064447:Checkpoint Kinase 2; D053614:Janus Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases