title: GATA1 mutations in patients with down syndrome and acute megakaryoblastic leukaemia do not always confer a good prognosis.
abstract: Children with Down syndrome and acute megakaryoblastic leukemia (DS-AMKL) have been shown to have increased sensitivity to cytarabine based chemotherapy. The excellent prognosis in patients with DS-AMKL may be due to mutations in the GATA1 gene leading to reduced expression of the enzyme cytidine deaminase. This leads to a decreased ability to convert cytarabine into its inactive metabolite, resulting in high intracellular concentration of this cytotoxic agent. We report two cases of DS-AMKL with GATA1 mutations who had poor outcome. These patients had high expression levels of cytidine deaminase mRNA transcripts. We speculate that other factors can affect overall outcome in patients with DS-AMKL irrespective of the presence of GATA1 mutations.
authors.affiliation: Department of Paediatrics, University of Malaya Medical Centre, Kuala Lumpur, Malaysia. hany@um.edu.my
authors.forename: Hany
authors.initials: H
authors.lastname: Ariffin
authors.forename: Jaime Castillo
authors.initials: JC
authors.lastname: Garcia
authors.forename: Siti Sarah
authors.initials: SS
authors.lastname: Daud
authors.forename: Kamariah
authors.initials: K
authors.lastname: Ibrahim
authors.forename: Nik
authors.initials: N
authors.lastname: Aizah
authors.forename: Gek-Bee
authors.initials: GB
authors.lastname: Ong
authors.forename: Lee-Ai
authors.initials: LA
authors.lastname: Chong
authors.forename: Zulqarnain
authors.initials: Z
authors.lastname: Mohamad
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001853:Bone Marrow / Q000473:pathology; D002675:Child, Preschool; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D004314:Down Syndrome / Q000150:complications / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D005260:Female; D050982:GATA1 Transcription Factor / Q000235:genetics*; D006801:Humans; D007223:Infant; D007947:Leukemia, Megakaryoblastic, Acute / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D009154:Mutation; D011379:Prognosis
chemical_list: D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; D003564:Cytidine Deaminase