CSF3R and CALR mutations in paediatric myeloid disorders and the association of CSF3R mutations with translocations, including t(8; 21). (9th April 2015)

• Record Type: Journal Article
• Authors: Sano, Hitoshi; Ohki, Kentaro; Park, Myoung‐ja; Shiba, Norio; Hara, Yusuke; Sotomatsu, Manabu; Tomizawa, Daisuke; Taga, Takashi; Kiyokawa, Nobutaka; Tawa, Akio; Horibe, Keizo; Adachi, Souichi; Hayashi, Yasuhide
• Is Part Of: British journal of haematology. Volume 170:Number 3(2015:Aug.)
• Page Start: 391
• Page End: 397
• Publication Date: 2015-04-09
• Subjects: Hematology -- Periodicals; Blood -- Diseases -- Periodicals; 616.15
• DOI: 10.1111/bjh.13439
• Languages: English
• ISSNs: 0007-1048

Abstract

<abstract abstract-type="main" id="bjh13439-abs-0001"> <title>Summary</title> <p>Mutations in the colony‐stimulating factor 3 receptor (<italic>CSF3R</italic>) and calreticulin (<italic>CALR</italic>) genes have been reported in a proportion of adults with myeloproliferative disease. However, little is known about <italic>CSF3R</italic> or <italic>CALR</italic> mutations in paediatric myeloid disorders. We analysed <italic>CSF3R</italic> exons 14 and 17, and <italic>CALR</italic> exon 9, using direct sequencing in samples of paediatric acute myeloid leukaemia (AML;<italic> n</italic> = 521), juvenile myelomonocytic leukaemia (JMML;<italic> n</italic> = 40), myelodysplastic syndrome (MDS;<italic> n</italic> = 20) and essential thrombocythaemia (ET;<italic> n</italic> = 21). <italic>CSF3R</italic> mutations were found in 10 (1·92%) of 521 patients with AML; two in exon 14 (both missense mutations resulting in p.T618I) and eight in exon 17 (three frameshift mutations: p.S715X, p.Q774R, and p.S783Q; and five novel missense mutations: p.Q754K, p.R769H, p.L777F, p.T781I, and S795R). All of the patients with mutations in <italic>CSF3R</italic> exon 17 had chromosomal translocations, including four with t(8;21). At the time of reporting, seven of these ten patients are alive; three have died, due to side effects of chemotherapy. No <italic>CSF3R</italic> mutations were found in cases of MDS, JMML or ET. The only mutation found in the <italic>CALR</italic> gene was a frameshift (p.L367 fs) in one ET patient. We discuss the potential impact of these findings for the leukaemogenesis and clinical features of paediatric myeloid disorders.</p> </abstract>