title: Molecular lesions in childhood and adult acute megakaryoblastic leukaemia.
abstract: While acute megakaryoblastic leukaemia (AMKL) occurs in children with (DS-AMKL) and without (paediatric non-DS-AMKL) Down syndrome, it can also affect adults without DS (adult non-DS-AMKL). We have analysed these subgroups of patients (11 children with DS-AMKL, 12 children and four adults with non-DS-AMKL) for the presence of molecular lesions, including mutations and chromosomal abnormalities studied by sequencing and single nucleotide polymorphism array-based karyotyping, respectively. In children, AMKL was associated with trisomy 21 (somatic in non-DS-AMKL), while numerical aberrations of chromosome 21 were only rarely associated with adult AMKL. DS-AMKL was also associated with recurrent somatic gains of 1q (4/11 DS-AMKL patients). In contrast to trisomy 21 and gains of 1q, other additional chromosomal lesions were evenly distributed between children and adults with AMKL. A mutational screen found GATA1 mutations in 11/12 DS-AMKL, but mutations were rare in paediatric non-DS-AMKL (1/12) and adult AMKL (0/4). JAK3 (1/11), JAK2 (1/11), and TP53 mutations (1/11) were found only in patients with DS-AMKL. ASXL1, IDH1/2, DNMT3A, RUNX1 and CBL mutations were not found in any of the patient group studied, while NRAS mutation was identified in two patients with paediatric non-DS-AMKL.
authors: Department of Paediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Asahito
authors: A
authors: Hama
authors: Hideki
authors: H
authors: Muramatsu
authors: Hideki
authors: H
authors: Makishima
authors: Yuka
authors: Y
authors: Sugimoto
authors: Hadrian
authors: H
authors: Szpurka
authors: Monika
authors: M
authors: Jasek
authors: Christine
authors: C
authors: O'Keefe
authors: Yoshiyuki
authors: Y
authors: Takahashi
authors: Hirotoshi
authors: H
authors: Sakaguchi
authors: Sayoko
authors: S
authors: Doisaki
authors: Akira
authors: A
authors: Shimada
authors: Nobuhiro
authors: N
authors: Watanabe
authors: Koji
authors: K
authors: Kato
authors: Hitoshi
authors: H
authors: Kiyoi
authors: Tomoki
authors: T
authors: Naoe
authors: Seiji
authors: S
authors: Kojima
authors: Jaroslaw P
authors: JP
authors: Maciejewski
mesh_terms: D000328:Adult; D017668:Age of Onset; D000782:Aneuploidy; D002648:Child; D002869:Chromosome Aberrations; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D004314:Down Syndrome / Q000150:complications / Q000235:genetics; D005260:Female; D052138:Genes, Neoplasm; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007621:Karyotyping; D007947:Leukemia, Megakaryoblastic, Acute / Q000145:classification / Q000150:complications / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide
chemical_list: D004273:DNA, Neoplasm; D009363:Neoplasm Proteins