title: De novo childhood myelodysplastic/myeloproliferative disease with unique molecular characteristics.
abstract: Myelodysplastic/myeloproliferative uclassifiable (MDS/MPN-U) is a rare myeloid neoplasm characterized by myelodysplasia and myeloproliferation at the time of initial presentation, which is usually a diagnosis of exclusion. The molecular pathogenesis of MDS/MPN-U patients remains to be elucidated. Among five patients diagnosed with MDS/MPN-U, three patients harboured RUNX1 (AML1) mutations; one carried somatic mosaicism of RUNX1 mutation with JAK2(V617F)  mutation and one had dual RUNX1 and FLT3-internal tandem duplication mutations with progression to acute myeloid leukaemia (AML). Germline mutation of TP53 was detected as a sole genetic lesion in one patient. JAK2(V617F)  and somatic mosaicism of KRAS and TET2 mutations co-existed in one patient. Otherwise, no alterations were detected in PTPN11, NRAS, CBL and ASXL1 genes. ETV6-PDGFRB fusion transcript was not detected in all patients. Four patients recieved haematopoietic stem cell transplantation (HSCT); three patients relapsed and one achieved complete remission after three donor lymphocyte infusions. Our findings suggest that the mutational spectrum observed in childhood MDS/MPN-U is quite different from that seen in juvenile myelomonocytic leukaemia and, to some extent, resemble chronic myelomonocytic leukaemia. Moreover, two patients had constitutional alterations of genes frequently found in AML. Further investigations are required to define the roles of these genetic alterations in the pathogenesis of childhood MDS/MPN-U.
authors.affiliation: Department of Paediatrics, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors.forename: Olfat
authors.initials: O
authors.lastname: Ismael
authors.forename: Akira
authors.initials: A
authors.lastname: Shimada
authors.forename: Asahito
authors.initials: A
authors.lastname: Hama
authors.forename: Momen
authors.initials: M
authors.lastname: Elshazley
authors.forename: Hideki
authors.initials: H
authors.lastname: Muramatsu
authors.forename: Aya
authors.initials: A
authors.lastname: Goto
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Sakaguchi
authors.forename: Makito
authors.initials: M
authors.lastname: Tanaka
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Xu
authors.initials: X
authors.lastname: Yinyan
authors.forename: Minoru
authors.initials: M
authors.lastname: Fukuda
authors.forename: Yuji
authors.initials: Y
authors.lastname: Miyajima
authors.forename: Yuka
authors.initials: Y
authors.lastname: Yamashita
authors.forename: Keizo
authors.initials: K
authors.lastname: Horibe
authors.forename: Ryoji
authors.initials: R
authors.lastname: Hanada
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ito
authors.forename: Seiji
authors.initials: S
authors.lastname: Kojima
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D002648:Child; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D049308:Dioxygenases; D005260:Female; D016158:Genes, p53; D018095:Germ-Line Mutation; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D054437:Myelodysplastic-Myeloproliferative Diseases / Q000235:genetics* / Q000473:pathology; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D016019:Survival Analysis
chemical_list: C473949:ASXL1 protein, human; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; C493728:RUNX1 protein, human; D012097:Repressor Proteins; D049308:Dioxygenases; C541081:TET2 protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11