Collection: Collection of Blood Research On June 18, 2020

The combination of EPCR defects and haemophilia joint diseasehttps://doi.org/10.1182/blood.2019003824coagulation factor VIIa (FVIIa) and endothelial cell protein C receptor (EPCR) can induce anti-inflammatory signals and protect the integrity of thevascularbarrierRecently, researchers explored the potential role of FVIIa and EPCR interactions in the pathogenesis of haemophilia and rFVIIa therapyin FVIII-/-mice, EPCR defects can significantly reduce the severity of hemophilia ponitary inflammationEPCR defects reduce IL-6 secretion, macrophage immersion and new angiogenic formation in the post-joint hemorrhage membraneA single dose of rFVIIa is sufficient to completelyprevent the occurrence of mild haemophilia inEPCR-/-FVIII-/-mouseThere was no significant difference between the occurrence of haemophilia joint disease in epCR high expression FVIII-/-mice with FVIII-/-mice, and 3 doses of rFVIIa had a partial protective effect on haemophilia in these miceConsistent with the epCR defect sepsis data to prevent haemophilia joint disease, single-dose EPCR blocking monoclonal antibodies can significantly reduce joint bleeding of FVIII-/- hemophilia gliophilis in mice2- miR-146a deficiency, IL6/TNFD induced inflammation and myelin malignancyhttps://doi.org/10.1182/blood.2019003105aging is associated with significant changes in the hematopoietic system, including increased inflammation, impaired function of hematopoieticstem cell(HSC), and increased incidence of myelin malignanciesAging inflammation (inflammage) is considered to be a driver of age-related changes in HSC function and myelin malignanciesRecent lying found that the absence of miR-146a in AML patients is a cause of aging-related inflammationin older wild mice, the expression of miR-146a decreased; in young mice with miR-146a deficiency, the absence of miR-146a promoted early aging and inflammation of HSC, and early aging-related myelin malignancies occurredThe resting, dry, differentiation potential and epigenetic state of HSC were determined by single-cell method to explore the function and group structure of HSC, and the absence of miR-146a was found to exhaust the original, stationary HSCs subgroupDNA methylation and transcription group spectrum suggest nf-B, IL-6, and TNF as potential drivers of HSC dysfunction, activate inflammatory signal transduction, and promote mature miR-146a-/-myelin and lymphocyte secretion OF IL6 and TNFReducing inflammation by targeting Il6 or Tnf is sufficient to restore the single-cell function and subgroup structure of miR-146a-/HSC and reduce the incidence of blood malignancies in miR-146a-/-miceThe increased sensitivity of miR-146a-/-HSCs to IL6 stimulation suggests that miR-146a deficiency can affect HSC function through extracellular inflammatory signals and increased intracellular inflammatory sensitivityLdb1 plays an important role in the autocancer gene Lmo-induced thymus cell self-renewal and T-ALLhttps://doi.org/10.1182/blood.2019000794the extension or expression enhancement of the primary cancer gene Lmo2 is associated with a severe acute T lymphoblastic leukemia (T-ALL), known as early T-progenitor all (ETP-ALL)Lmo2 has long been thought to function as part of a multi-kilo transcription complex that contains the ubiquitous adapter Ldb1 and b-HLH and/or GATA family transcription factors, but lacks experimental evidence to directly support the mechanismrecently, researchers in the Lmo2 genetically modified mouse T-ALL model, by conditioning the removal of Ldb1 in thymus cells to study the significance of Ldb1 in Lmo2 induced T-ALLThe results show edited that Ldb1 plays a vital role in Lmo2 induced thymus cell self-renewal and thymus cell resistance, as well as pre-leukemia thymus cell-dominant T-ALL transitionIn addition, Ldb1 is also involved in the acquisition of pre-ETP gene expression characteristics in immature Lmo2 genetically modified thymus cells In pre-leukemia Lmo2 genetically modified thymus cells, a combination of Ldb1 and Lmo2 was found on the promoters of the key uplifted T-ALL-driven genes (Hhex, Lyl1 and Nfe2), while the combination of Ldb1 and Lmo2 was reduced after the absence of Cre-mediated Ldb1 btK inhibitor therapy can be effective in treating venetoclax drug resistance https://doi.org/10.1182/blood.2020004782 highly active BTK inhibitors (BTKi) and BCL2 inhibitorvenetoclax change the therapeutic prospects of chronic lymphoblastic leukemia (CLL) Clinical trial results showed that venetoclax had good efficacy for patients with progression in the after-treatment of BTKi, but data on the progression of CLL patients following venetoclax treatment were limited, especially in terms of durability recent researchers reviewed 23 cases of recurrent/refractory CLL treatment in BTKi (Irutinib: 21 cases; zanubrutinib: 2) after venetoclax treatment The median progression-free survival period and median overall survival period after BTKi therapy were 34 months and 42 months, respectively The duration of the early remission at venetoclax treatment, which is 24 months, and residual lesions that are fully remissioned or undetectable, are associated with longer PFS at BTKi-saving treatment Patients with BCL2 Gly101Val Venetoclax drug-resistant mutations with BTKi therapy can achieve long-lasting results (estimated to be 69% pfS at 24 months) Source: MedSci Original