GATA1 mutations in patients with down syndrome and acute megakaryoblastic leukaemia do not always confer a good prognosis.
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.
Ariffin
Hany
H
Department of Paediatrics, University of Malaya Medical Centre, Kuala Lumpur, Malaysia. hany@um.edu.my
Garcia
Jaime Castillo
JC
Daud
Siti Sarah
SS
Ibrahim
Kamariah
K
Aizah
Nik
N
Ong
Gek-Bee
GB
Chong
Lee-Ai
LA
Mohamad
Zulqarnain
Z
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
D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; D003564:Cytidine Deaminase