title: CSF3R and CALR mutations in paediatric myeloid disorders and the association of CSF3R mutations with translocations, including t(8; 21).
abstract: Mutations in the colony-stimulating factor 3 receptor (CSF3R) and calreticulin (CALR) genes have been reported in a proportion of adults with myeloproliferative disease. However, little is known about CSF3R or CALR mutations in paediatric myeloid disorders. We analysed CSF3R 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). CSF3R mutations were found in 10 (1.2%) 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 CSF3R 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 CSF3R 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.
authors: Department of Haematology/Oncology, Gunma Children's Medical Centre, Shibukawa, Japan.
authors: Hitoshi
authors: H
authors: Sano
authors: Department of Haematology/Oncology, Gunma Children's Medical Centre, Shibukawa, Japan.
authors: Kentaro
authors: K
authors: Ohki
authors: Department of Haematology/Oncology, Gunma Children's Medical Centre, Shibukawa, Japan.
authors: Myoung-Ja
authors: MJ
authors: Park
authors: Department of Haematology/Oncology, Gunma Children's Medical Centre, Shibukawa, Japan.|Department of Paediatrics, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors: Norio
authors: N
authors: Shiba
authors: Department of Haematology/Oncology, Gunma Children's Medical Centre, Shibukawa, Japan.|Department of Paediatrics, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors: Yusuke
authors: Y
authors: Hara
authors: Department of Haematology/Oncology, Gunma Children's Medical Centre, Shibukawa, Japan.
authors: Manabu
authors: M
authors: Sotomatsu
authors: Division of Leukaemia and Lymphoma, Children's Cancer Centre, National Centre for Child Health and Development, Tokyo, Japan.
authors: Daisuke
authors: D
authors: Tomizawa
authors: Department of Paediatrics, Shiga University of Medical Science, Shiga, Japan.
authors: Takashi
authors: T
authors: Taga
authors: Department of Paediatric Haematology and Oncology Research National Research Institute for Child Health and Development, Tokyo, Japan.
authors: Nobutaka
authors: N
authors: Kiyokawa
authors: Department of Paediatrics, National Hospital Organization Osaka National Hospital, Osaka, Japan.
authors: Akio
authors: A
authors: Tawa
authors: Department of Paediatrics, National Hospital Organization Nagoya Medical Centre, Nagoya, Japan.
authors: Keizo
authors: K
authors: Horibe
authors: Department of Human Health Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: Souichi
authors: S
authors: Adachi
authors: Department of Haematology/Oncology, Gunma Children's Medical Centre, Shibukawa, Japan.
authors: Yasuhide
authors: Y
authors: Hayashi
mesh_terms: D000293:Adolescent; D000328:Adult; D037282:Calreticulin / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D005091:Exons; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality; D008297:Male; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000401:mortality; D016184:Receptors, Colony-Stimulating Factor / Q000235:genetics*; D013920:Thrombocythemia, Essential / Q000235:genetics* / Q000401:mortality; D014178:Translocation, Genetic
chemical_list: C576483:CALR protein, human; C517047:CSF3R protein, human; D037282:Calreticulin; D016184:Receptors, Colony-Stimulating Factor
keywords: CALR; CSF3R; children; myeloid disorder