Complexity of chromosomal rearrangements in Down syndrome leukemia

Reports on imbalanced HSA21 gene expression and chromosomal rearrangements on leukemogenesis, drug sensitivity, and treatment outcome of leukemia in Down syndrome (DS) are limited. DS has been recognized as one of the most common leukemia-predisposing syndromes with unique clinical features, significant differences in treatment outcome and treatment-related toxicity profiles. Acute myeloid leukemia (AML), especially acute megakaryocytic leukemia, is reported with high cure rates presenting 80%-100% event-free survivals (EFSs); however, acute lymphoid leukemia indicates a worse prognosis in DS patients compared to non-DS children. Complex rearrangements are responsible for poor-to-very poor prognosis in all cases, irrespective of genetic predisposition or type of hematopoietic subunits affected. We report a 2-year-old female DS diagnosed with acute erythroleukemia (French-American-British: AML-M6) with highly complex chromosomal rearrangements in the bone marrow with 39 chromosomes. Parental consanguinity and genetic predisposition might be responsible for origin of multiple clones. Genetic instability and heterogeneity of complex clonal developments might cause poor prognosis. The case is a rare one with acute erythroleukemia in DS patient where too many rearrangements had masked identification of three 21s.