"Stocking up" On July 2, 2020 Blood Research Select

1: in acute lymphoblastic leukemia,E2A-PBX1is a secondary activation factorRUNX1E2A is a basic helical-ring-helix (bHLH) transcription factor that plays a vital role in determining the fate of tissue-specific cells, including B cell lineage differentiationIn 5% ofchildrenacute lymphoblastic leukemia (ALL), the t (1,19) chromosome translocation specifically targets the E2A gene, producing a cancer-causing E2A-PBX1 fusion proteinRecently, researchers identified the direct target site of E2A-PBX1 in t (1,19) positive pre-B ALL, and found that E2A-PBX1 prioritizes a subset of gene sites (p300, MED1, and HK27 acetylation) combined with RUNX1 and gene activation mechanisms compared to normal E2AThrough biochemical analysis, it is further discovered that E2A-PBX1 interacts directly with RUNX1 through a region that spans the PBX1 homologous domainThe results also show that the binding of E2A-PBX1 to gene enhancers depends on interaction with RUNX1, not on DNA binding activity in the E2A-PBX1 homologous domainTranscriptogroup analysis and cell transformation analysis further established the e2A-PBX1-mediated target gene activation and the important RUNX1 requirements for leukemiaIt is worth noting that the RUNX1 bit itself is also directly activated by E2A-PBX1, indicating that there is a multi-layered interaction between E2A-PBX1 and RUNX12CyBorD , a combination of daremus monobagain, is the newly diagnosed AL although no treatment for light chain (AL) amyloid has yet been approved, cyclophosatine, botimizomi and Cybord are considered standard treatments for newly diagnosed patients Based on the safety and efficacy of anti-CD38 antibody daratumab (Daremu monosar) in multiple myeloma (MM), the Phase 3 ANDROMEDA study compared the efficacy of Daremu monoantirapy-CyBorD and CyBorD treatment for newly diagnosed AL amyloid the median age of the subjects was 67.5 years, the median time from diagnosis to enlistment test was 59.5 days, the median affected organ was 2, and 68% and 61% of the patients were suffering from kidney and heart conditions, respectively The median course of treatment is 16 The most common adverse reactions requiring emergency treatment were diarrhea (68%), fatigue (54%) and peripheral edema (50%), consistent with the safety of MM and CyBorD treated with DARA SC In 11 patients, the injection-related reaction seise No adverse reactions associated with level 5 treatment were not, 5 patients died and 3 patients underwent of self-
stem cells The overall remission rate of hematology was 96%, 23 (82%) patients received very good partial remission, 15 (54%) patients received full remission, and 20, 22 and 17 patients received at least partial remission at the first, third and sixth months, respectively Organ remission rate was 64% (median follow-up 17.6 months) At the 3rd, 6th and 12th months, 6/16, 7/15 and 10/15 patients received renal remission, and 6/16, 6/13 and 8/13 patients received cardio
vascular remission, respectively In addition, at 12 months, two out of 3 patients who had liver condition received liver remission 3) mitochondrial vector homologous gene MTCH2 is essential for the survival of AML in order to identify the mitochondrial gene required for cell growth of AML (acute myeloid leukemia) cells, the researchers used CRISPR technology for screening, analysis and identification of mitochondrial in vitro membrane protein MTCH2 (mitochondrial carrier homologous 2) In AML cells, knocking down the expression of MTCH2 inhibits cell growth, reduces the transplant potential of stem cells and induces the cell differentiation process Inhibiting the expression of MTCH2 in AML cells can increase the expression level of acetone acid and acetone dehydrogenase in the nucleus, thereby inducing acetylation of histones and promoting differentiation of AML cells 4) Acalabrutinib the treatment of slow gonorrhea leukemia and the efficacy of inhibittheon of B-cell receptor pathways, in particular Bruton tyrosine kinase (BTK), is the main strategy for the treatment of B-cell malignancies, including chronic lymphocytic leukemia (CLL) Target occupancy is a measure of BTK covalent binding and has been used as an efficacy parameter in the clinical study of BTK inhibitors However, the relationship between the dynamics (determining occupancy) and occupancy of BTK from scratch, path inhibition and clinical prognosis remains uncertain a phase 2 randomized trial in which 48 patients were recruited The results showed good tolerance of acalabrutinib, with an overall remission rate (ORR) of 95.8% in patients treated with ABID dose, and an expected 2-year progression-free survival rate (PFS) of 87.2%, orR of 79.2% in patients treated with QD dose and 87.2% (95% CI 57.2%-96.7%) in 2 years BTK resynthetic in CLL patients was faster than that of healthy volunteers Compared to the QD dose, the BID dose maintains a higher BTK occupancy and achieves more effective pathway suppression Compared to the QD dose, the share of THE BID dose increases slightly over time, thus enhancing the downstream biological effects The effect of BTK possession on clinical long-term prognosis has yet to be determined AGK defects can lead to abnormal differentiation of macronuclear cells and platelet reduction macronucleocyte sylophone development abnormalities and platelet production abnormalities can lead to platelet reduction or platelet growth, increased bleeding or the risk of thrombosis AGK is a mitochondrial membrane kinase that catalyzes the formation of phospholipid acid and hemolytic phospholipid acid It has been identified that AGK mutation is the main cause of Sengers syndrome, and patients with Sengers syndrome have been reported to show decreased platelets In this study, researchers found that mice with large nuclear cells/platelet-specific AGK defects developed platelet reduction and spleen enlargement, mainly caused by ineffective bone marrow platelet production and excessive myelin, but not for circulating platelet apoptosis it has been reported that the G126E mutation weakens AGK kinase activity The researchers found that the AGK G126E mutation did not affect peripheral platelet count or macronuclear cell differentiation, suggesting that AGK's involvement in macronuclear cell development and platelet biological occurrence did not depend on its kinase activity Source: MedSci Original