Open AccessClinical and biological aspects of myeloid leukemia in Down syndrome
Author(s) -
Austin Boucher,
Kenneth J. Caldwell,
John D. Crispino,
Jamie E. Flerlage
Publication year - 2021
Publication title -
leukemia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.539
H-Index - 192
eISSN - 1476-5551
pISSN - 0887-6924
DOI - 10.1038/s41375-021-01414-y
Subject(s) - myelopoiesis , down syndrome , myeloid leukemia , gata1 , medicine , leukemia , acute megakaryoblastic leukemia , myeloid , oncology , malignancy , epigenetics , azacitidine , immunology , bioinformatics , progenitor cell , cancer research , biology , stem cell , dna methylation , genetics , erythropoiesis , gene expression , psychiatry , gene , anemia
Children with Down syndrome are at an elevated risk of leukemia, especially myeloid leukemia (ML-DS). This malignancy is frequently preceded by transient abnormal myelopoiesis (TAM), which is self-limited expansion of fetal liver-derived megakaryocyte progenitors. An array of international studies has led to consensus in treating ML-DS with reduced-intensity chemotherapy, leading to excellent outcomes. In addition, studies performed in the past 20 years have revealed many of the genetic and epigenetic features of the tumors, including GATA1 mutations that are arguably associated with all cases of both TAM and ML-DS. Despite these advances in understanding the clinical and biological aspects of ML-DS, little is known about the mechanisms of relapse. Upon relapse, patients face a poor outcome, and there is no consensus on treatment. Future studies need to be focused on this challenging aspect of leukemia in children with DS.