Mutations profile of polycythemia vera and essential thrombocythemia among Japanese children

• Published in: Pediatric blood & cancer Vol. 59; no. 3; pp. 530 - 535
• Main Authors: Ismael, Olfat, Shimada, Akira, Hama, Asahito, Sakaguchi, Hiroshi, Doisaki, Sayoko, Muramatsu, Hideki, Yoshida, Nao, Ito, Masafumi, Takahashi, Yoshiyuki, Akita, Naohiro, Sunami, Shosuke, Ohtsuka, Yoshitoshi, Asada, Youji, Fujisaki, Hiroyuki, Kojima, Seiji
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.09.2012
• Subjects: Adolescent; Asian Continental Ancestry Group; ASXL1; Child; Child, Preschool; essential thrombocythemia; Female; Humans; Infant; JAK2; Janus Kinase 2 - genetics; Male; Mutation; polycythemia vera; Polycythemia Vera - genetics; Thrombocythemia, Essential - genetics
• ISSN: 1545-5009; 1545-5017
• DOI: 10.1002/pbc.23409

Background Acquired somatic mutations of JAK2 have been reported to play a pivotal role in the pathogenesis of BCR‐ABL1‐negative myeloproliferative neoplasm (MPN). However, the molecular characteristics of childhood MPN remain to be elucidated. Patient and Methods We investigated a group of pediatric patients diagnosed either with essential thrombocythemia (ET; N = 9) or polycythemia vera (PV; N = 4) according to WHO criteria (median age = 10 years; range 1.5–15 years) in whom direct sequencing was performed for the existence of genetic alterations in JAK2, MPL, TET2, ASXL1, CBL, IDH1, and IDH2. More sensitive allele specific polymerase chain reaction was used for JAK2V617F genotyping. Results We found three patients harbor JAK2V617F mutation (2/9 ET and 1/4 PV). Bone marrow examination showed small and large megakaryocytes with dysplastic features in JAK2V617F‐positive ET patients compared to those without JAK2V617F. We identified a previously unrecognized missense mutation at codon 1230 in exon 12 of ASXL1 gene in ET and PV patients (1/9 ET and 1/4 PV). Otherwise, no genetic alterations could be detected in JAK2 exon 12, MPL, TET2, CBL, IDH1, and IDH2 in all ET and PV patients. Conclusion Although JAK2 mutations in childhood ET and PV are not as frequent as reported in adult patients, JAK2 is the most frequently mutated gene in childhood MPN known so far. Owing to the presence of childhood MPN without any genetic alterations in JAK2, MPL, TET2, ASXL1, CBL, IDH1, and IDH2, new biological markers have to be found. Pediatr Blood Cancer 2012;59:530–535. © 2011 Wiley Periodicals, Inc.