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CSF 3R and CALR mutations in paediatric myeloid disorders and the association of CSF 3R mutations with translocations, including t(8; 21)
Author(s) -
Sano Hitoshi,
Ohki Kentaro,
Park Myoungja,
Shiba Norio,
Hara Yusuke,
Sotomatsu Manabu,
Tomizawa Daisuke,
Taga Takashi,
Kiyokawa Nobutaka,
Tawa Akio,
Horibe Keizo,
Adachi Souichi,
Hayashi Yasuhide
Publication year - 2015
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.13439
Subject(s) - missense mutation , frameshift mutation , exon , juvenile myelomonocytic leukemia , myeloid , medicine , calreticulin , mutation , cancer research , myelodysplastic syndromes , chromosomal translocation , immunology , biology , gene , genetics , stem cell , haematopoiesis , bone marrow , endoplasmic reticulum
Summary Mutations in the colony‐stimulating factor 3 receptor ( CSF 3R ) and calreticulin ( CALR ) genes have been reported in a proportion of adults with myeloproliferative disease. However, little is known about CSF 3R or CALR mutations in paediatric myeloid disorders. We analysed CSF 3R exons 14 and 17, and CALR exon 9, using direct sequencing in samples of paediatric acute myeloid leukaemia ( AML ; n = 521), juvenile myelomonocytic leukaemia ( JMML ; n = 40), myelodysplastic syndrome ( MDS ; n = 20) and essential thrombocythaemia ( ET ; n = 21). CSF 3R 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 CSF 3R 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 CSF 3R mutations were found in cases of MDS , JMML or ET . The only mutation found in the CALR 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.