The increased risk of transient myeloproliferative disorder (TMD) and acute myeloid leukemia (AML) during early childhood in Down syndrome (DS) has stimulated research related to the role of trisomy 21 in the development of hematological neoplasm. The unique biological features of TMD including spontaneous resolution in the majority of cases, the increased risk of developing AML (25%) following resolution of TMD and the superior outcome of DS AML patients with cytarabine-based regimens highlight further areas of research interest. Alteration of intracellular redox reaction kinetics secondary to increased expression of chromosome 21-localized genes (e.g. superoxide dismutase) and the associated changes in apoptotic responses in DS tissues, may account for the increased sensitivity of DS myeloblasts to chemotherapy agents. The identification of the pharmacological and molecular basis for the increased sensitivity of DS myeloblasts to cytarabine and daunorubicin based on altered expression of chromosome 21-localized genes may ultimately lead to improvements in the therapy of AML in non-DS individuals.
- Acute myeloid leukemia
- Down syndrome
- Drug metabolism
- Free radicals
- Transient myeloproliferative disorder