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

• Published in: Haematologica (Roma) Vol. 97; no. 3; pp. 366 - 370
• Main Authors: JANISZEWSKA, Hanna, BAK, Aneta, HAUS, Olga, PILARSKA, Maria, HEISE, Marta, JUNKIERT-CZARNECKA, Anna, KULISZKIEWICZ-JANUS, Małgorzata, CALBECKA, Małgorzata, JAZWIEC, Bożena, WOLOWIEC, Dariusz, KULICZKOWSKI, Kazimierz
• Format: Journal Article
• Language: English
• Published: Pavia Ferrata Storti Foundation 01.03.2012
• Subjects: Adult; Age Factors; Aged; Aged, 80 and over; Biological and medical sciences; Checkpoint Kinase 2; DNA Mutational Analysis; Female; Genetic Predisposition to Disease; Germ-Line Mutation; Hematologic and hematopoietic diseases; Heterozygote; Humans; Janus Kinase 2 - genetics; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Middle Aged; Mutation; Original and Brief Reports; Pedigree; Protein-Serine-Threonine Kinases - genetics; Risk; Thrombocythemia, Essential - genetics; Young Adult; Serine/threonine-protein kinase Chk2; Myeloproliferative syndrome; Essential thrombocythemia; congenital CHEK2 mutations; Congenital; Gene; Hematology; Risk factor; Genetics; Malignant hemopathy; Mutation; Cancer
• ISSN: 0390-6078; 1592-8721
• DOI: 10.3324/haematol.2011.049494

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.