Transcription factor mutations as a cause of familial myeloid neoplasms.

摘要: The initiation and evolution of myelodysplastic syndrome (MDS) acute myeloid leukemia (AML) are driven by genomic events that disrupt multiple genes controlling hematopoiesis. Human genetic studies have discovered germline mutations in single instigate familial MDS/AML. best understood these encode transcription factors, such as GATA-2, RUNX1, ETV6, C/EBPα, which establish maintain networks governing the genesis function blood stem progenitor cells. Many questions remain unanswered regarding how circuits within physiology disease whether network integrity is exquisitely sensitive to or efficiently buffered from perturbations. In MDS/AML, change coding sequence a gene generate mutant protein with altered activity introduce frameshifts stop codons regulatory elements alter expression. Each mutation has potential exert quantitatively qualitatively distinct influences on networks. Consistent this mechanistic diversity, onset unpredictable phenotypic variability can be considerable. Efforts elucidate mechanisms forge prognostic therapeutic strategies must therefore contend spectrum patient-specific leukemogenic scenarios. Here we illustrate advances our understanding MDS/AML syndromes caused hematopoietic factors.