.Children with Down syndrome manifest multiple hematologic manifestations: (1) transient
myeloproliferative disorder (TMD)/transient abnormal myelopoiesis (TAM) at birth, (2)
acute myeloid leukemia (ML-DS), and (3) acute lymphoblastic leukemia (ALL).
.The underlying primary basis for the varied hematologic manifestations is linked to the
gene dosage effect of chromosome 21–encoded genes.
. TMD/TAM and ML-DS are characterized by the presence of truncating mutations in exon
2 of the hematopoietic transcription factor GATA1. Spontaneous resolution is common in
TMD/TAM, and ML-DS is highly responsive to chemotherapy with resultant high cure rates
compared with acute myeloid leukemia in non-DS children.
.DS-ALL is characterized by the presence of mutations in JAK2 tyrosine kinase and IKZF1.
In contrast to the high cure rates in ML-DS, the results in DS-ALL are same are inferior to
non-DS ALL, in part, because of the lower frequency of good-response ALL subtypes and
also the higher systemic toxicity of agents used in children with DS.
Superintendent, ICH.