Megakaryoblastic Leukemia and Down's Syndrome: A Review

Abstract

Megakaryoblastic leukemia and transient leukemia in Down's syndrome have been reviewed using case reports from the literature and our own experience at the Hospital for Sick Children. The following conclusions have been reached: (1) approximately 20% of leukemia (excluding transient leukemia) in Down's syndrome is acute megakaryoblastic leukemia; (2) approximately 20% of all leukemia in Down's syndrome is transient leukemia; (3) transient leukemia in Down's syndrome is acute megakaryoblastic leukemia; (4) recurrence of acute megakaryoblastic leukemia occurs in 20% of the cases of transient leukemia; and (5) the incidence of acute megakaryoblastic leukemia in Down's syndrome is estimated to be 400 times that in normal children. These observations suggest that a specific form of leukemia, namely acute megakaryoblastic leukemia, has a remarkable association with Down's syndrome.

Antigen expression patterns reflecting genotype of acute leukemias

“…220,221 AMKL with t(1;22) is most frequent in infants (20% of all infant AML). 66,222 It is less common in older children (4%) or adults (2-8%). 223,224 Diagnosis of AMKL is primarily based on ultrastructural demonstration of platelet peroxidase.…”

Developmental differences in IFN signaling affect GATA1s-induced megakaryocyte hyperproliferation

“…Individuals with Down syndrome (DS) have a 10-to 20-fold higher overall risk of leukemia than do non-DS individuals (1)(2)(3). A substantial proportion of these excess cases is due to acute megakaryoblastic leukemia (DS-AMKL) during early childhood.…”

Cytogenetic features of acute lymphoblastic and myeloid leukemias in pediatric patients with Down syndrome: an iBFM-SG study

“…[3][4][5] This, together with the fact that acquired gain of chromosome 21 occurs in approximately 20% and 5% of cytogenetically abnormal ALL and AML, respectively, 6 clearly suggests that ϩ21 is strongly associated with leukemogenesis. Since ϩ21 in individuals with DS is present both in the leukemic as well as in the nonleukemic cells, its leukemogenic impact may be either cell autonomous, having a direct oncogenic effect, or non-cell autonomous, affecting the microenvironment.…”