title: Spectrum of molecular defects in juvenile myelomonocytic leukaemia includes ASXL1 mutations.
abstract: Mutations in NF1, PTPN11, NRAS, KRAS and CBL have been reported to play a pathogenetic role in juvenile myelomonocytic leukaemia (JMML), a rare myelodyplastic/myeloproliferative neoplasm occurring in children. Recently, mutations in ASXL1 were identified in chronic myelomonocytic leukaemia and other myeloid malignancies. We sequenced exon 12 of ASLX1 in 49 JMML patients, and found 2 novel heterozygous (nonsense and frameshift) mutations, one occurring as a sole lesion, the other was in conjunction with a PTPN11 mutation. ASXL1 cooperates with KDM1A in transcriptional repression and thereby ASXL1 mutations may synergize with or mimic other JMML-related mutations.
authors.affiliation: Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Sugimoto
authors.forename: Hideki
authors.initials: H
authors.lastname: Muramatsu
authors.forename: Hideki
authors.initials: H
authors.lastname: Makishima
authors.forename: Courtney
authors.initials: C
authors.lastname: Prince
authors.forename: Anna M
authors.initials: AM
authors.lastname: Jankowska
authors.forename: Nao
authors.initials: N
authors.lastname: Yoshida
authors.forename: Yinyan
authors.initials: Y
authors.lastname: Xu
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Nishio
authors.forename: Asahito
authors.initials: A
authors.lastname: Hama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yagasaki
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Koji
authors.initials: K
authors.lastname: Kato
authors.forename: Atsushi
authors.initials: A
authors.lastname: Manabe
authors.forename: Seiji
authors.initials: S
authors.lastname: Kojima
authors.forename: Jaroslaw P
authors.initials: JP
authors.lastname: Maciejewski
mesh_terms: D002675:Child, Preschool; D018389:Codon, Nonsense; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D007223:Infant; D007621:Karyotyping; D054429:Leukemia, Myelomonocytic, Juvenile / Q000235:genetics*; D008297:Male; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics*
chemical_list: C473949:ASXL1 protein, human; D018389:Codon, Nonsense; D009363:Neoplasm Proteins; D012097:Repressor Proteins; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11