Blood: Genetic-transcription analysis identifies key transcription factors as drivers of human leukemia

Acute erythritosa (AML-M6 or AEL) is a rare invasive blood malignant tumorPrevious studies have shown that AEL leukemia cells often carry complex nucleotypes and mutations of known AML-related cancer genesto better define the potential molecular mechanisms that drive red line phenotypes, the researchers studied 33 AEL samples representing three genetic subgroups of AEL, including TP53 mutations, epigenetic regulator mutations (such as DNMT3A, TET2, or IDH2), and cases of undefined low mutation loadsresearchers created a "space" based on transcriptionomics based on red lines vs myelin, in which most AEL samples showed different unique positioning than those of non-M6 AML and bone marrow hyperplasia syndrome, independent of the molecular subgroups mentioned aboveIt is worth noting that more than 25% of AEL patients , including genetically uncertain subgroups, showed abnormal expression of key transcription factors, including SKI, ERG, and ETO2The ectopic expression of these factors in the red precursor cells of mice hindered in vitro differentiation of the red line, leading to permanent biochemistry, which was associated with reduced chromatin accessibility of GATA1 binding sites and functional interference with GATA1 activityin vivo models show that the occurrence of deadly red, red/myelin-like hybrids, or other malignant tumors depends on the cell population that expresses a.daEL-related mutationsin summary, this study suggests that AEL is a molecular heterogeneous disease with red linehomogene, in part due to the abnormal activity of key red line transcription factors in hematopoietic stem cells or progenitor cells