Individuals with Down syndrome (DS) frequently have hematopoietic abnormalities, including transient myeloproliferative disorder and acute megakaryoblastic leukemia which are often accompanied by acquired GATA1 mutations that produce a truncated protein, GATA1s.
Intense GATA1 nuclear expression is a sensitive and specific marker for cells of erythroid and megakaryocytic lineages and is an excellent marker for neoplastic cells of pure erythroleukemia and acute megakaryoblastic leukemia.
In particular, the somatic mutation of the GATA1 gene, which leads to the production of N-terminally truncated GATA1, contributes to the genesis of transient myeloproliferative disorder and acute megakaryoblastic leukemia in infants with Down syndrome.
The proproliferative effect of miR-125b-2 on MEPs accentuated the Gata1s mutation, whereas growth of DS-AMKL/TL cells was impaired upon miR-125b repression, suggesting synergism during leukemic transformation in GATA1s-mutated DS-AMKL/TL.
Tetrasomy 21 as a sole acquired abnormality without GATA1 gene mutation in pediatric acute megakaryoblastic leukemia: a case report and review of the literature.
We have generated mice from a N-ethyl-N-nitrosourea mutagenesis screen that carry a mutation in the translation initiation codon of Gata-1, termed Plt13, which is equivalent to mutations found in patients with acute megakaryoblastic leukemia and Down syndrome.
Acquired somatic mutations in exon 2 of the hematopoietic transcription factor GATA-1 have been found in individuals with Down syndrome with both transient myeloproliferative disorder and acute megakaryoblastic leukemia.
Finally, the inability of GATA-1s to promote expression of important metabolic genes, such as cytadine deaminase, likely contributes to the remarkable hypersensitivity of AMkL blasts to cytosine arabinoside.
Acquired mutations in the hematopoietic transcription factor GATA binding protein-1 (GATA1) are found in megakaryoblasts from nearly all individuals with Down syndrome with transient myeloproliferative disorder (TMD, also called transient leukemia) and the related acute megakaryoblastic leukemia (DS-AMKL, also called DS-AML M7).
GATA1 mutations in Down syndrome: implications for biology and diagnosis of children with transient myeloproliferative disorder and acute megakaryoblastic leukemia.
Mutations in the GATA-1 gene have been identified in patients with familial macrothrombocytopenia and Down's syndrome patients with a transient myeloproliferative disorder and/or acute megakaryoblastic leukemia.
We present a case of acute megakaryoblastic leukemia with t(1;22)(p13;q13) along with a discussion of the current understanding of the molecular biology of RBM15-MKL1.
Collectively, these functional and spatial changes of OTT and BSAC caused by the fusion might perturb their functions, culminating in the development of acute megakaryoblastic leukemia.
We present a case of acute megakaryoblastic leukemia with t(1;22)(p13;q13) along with a discussion of the current understanding of the molecular biology of RBM15-MKL1.