Take stock: A selection of Blod research on October 29, 2020

1. Intestinal bacteria disorders lead to an increased risk of leukemia in mice https://doi.org/10.1182/blood.2019004381 Most childhood leukemias are pregenital B-cell acute lymphoblastic leukemia (pB-ALL), caused by pre-birth genetic susceptibility and post-birth carcinogenic events.
although genetic susceptivity is common in children, less than 1% of genetic susceptible carriers develop pB-ALL.
recently, researchers used a pB-ALL mouse model to demonstrate that microbiome disorders caused by early-life antibiotic treatment were sufficient to induce leukemia in genetically susceptible mice.
by sequencing V4 and full length 16SrRNA in a series of fecal samples, the researchers found that mice with pB-ALL genetic susceptivity (Pax5 hybrid or ETV6-RUNX1 fusion variant) had a different gut microbiome than mice without genetic susceptivity.
machine learning accurately predicted genetic susceptivity (96.8%) using 40 of the 3,983 amplification sequence variants (ASVs) as alternatives to bacterial species.
the wild type (WT) or Pax5 plus/- hematocyte bone marrow cells were transplanted to the WT-recipient mice, and it was found that the microbiome of the recipient mice gradually changed to the microbiome of the donor mice.
gas chromatography-mass spectrometrometrometromety (GC-MS) analysis of serums in WT and Pax5 plus/- mice showed the existence of a unique metabolic spectrum specific to genotypes.
2: The clinical success of butinib's treatment of Fahrenheit globulinemia Phase II https://doi.org/10.1182/blood.2020006449 Fahrenheit jumboglobulinemia (WM) ), a rare non-Hodgkin's lymphoma, lymphocyte lymphoma, the patient manifests as mouth and nose haemorrhage, anemia, decreased levels of fibrinogen in the blood, swollen lymph nodes, a large number of proliferating plasma cells in the bone marrow, and due to a large increase in globulin caused by blood viscosity.
Bruton tyrosine kinase (BTK) inhibitors show therapeutic activity in Fahrenheit globulinemia.
Zanubrutinib, a selective BTK inhibitor, was approved by the FDA in November 2019 to treat patients with previously treated heterocellular lymphoma (MCL).
trotman and others recently conducted a Phase 1/2 clinical trial to assess the efficacy of Zebutini for primary treatment (TN) or relapse/resoic (R/R) WM.
two Zebtini oral solutions: 160 mg 2/day (n=50) or 320 mg 1/day (n=23).
end points include overall remission rate (ORR) and very good partial/complete remission (VGPR/CR).
September 2014 - March 2018, a total of 77 patients (24 TN and 53 R/R) were treated.
36 months and 23.5 months after the mid-level follow-up of R/R patients and TN patients, 72.7 percent of patients were still receiving treatment.
adverse reactions (13 per cent, 1 treatment-related), disease progression (10.4 per cent) and other (3.9 per cent) causes of termination of treatment.
ORR and VGPR/CR rates were 95.9% and 45.2%, respectively, and VGPR/CR rates increased over time: 20.5% at 6 months, 32.9% at 12 months and 43.8% at 24 months.
the three-year non-progress survival rate of 80.5 per cent and the overall survival rate of 84.8 per cent.
adverse reactions were caused by bruising (32.5 per cent, all level 1), a reduction in neutral granulocytes (18.2 per cent), hemorrhage (3.9 per cent), atrial fibrillation/atrial paralycergic (5.2 per cent) and stage 3 diarrhea (2.6 per cent).
Zebtini vs Erutini treats Fahrenheit globulinemia https://doi.org/10.1182/blood.2020006844 Bruton Tyrosine kinase (BTK) inhibitors are an effective treatment for Fahrenheit globulinemia (WM).
a Phase 3 Aspen study conducted by Constantine S. Tam and others recently compared the efficacy and safety of the first generation of BTK inhibitor erutinib and the new highly selective BTK inhibitor Zebutinib in patients with Fahrenheit globulinemia.
201 patients with myD88L265P mutation were randomly assigned to the Irudinie and Zebtinie groups at 1:1.
end point is a completely or very good partial mitigation (CR or VGPR) rate.
key secondary endpoints include major mitigation rates (MRRs), progress-free survival rates (PFS), mitigation duration (DOR), disease burden, and safety.
199 patients received at least one dose of the study.
patients get CR.
29 (28%) and 19 (19%) patients in the Zebtini and Erutini groups received VGPR, respectively, but the differences between the two groups were not statistically significant (P-0.09);
did not reach the mid-level DOR and PFS, and the 18-month progress-free survival rates in the Erutini and Zebtini groups were 84 per cent and 85 per cent, respectively.
in the Zebtini group, the incidence of atrial fibrillation, bruising, diarrhea, extrinsic edema, bleeding, muscle spasms and pneumonia, as well as adverse events leading to discontinuation of treatment, were lower.
Although the ≥ level 3 infection rates were similar in both groups (1.2% and 1.1%/100 person-months, respectively), the risk of neutrocyte reduction was higher in patients treated with zebtinib.
: High expression CXCL4 promotes progression of MPN bone marrow fibrosis https://doi.org/10.1182/blood.2019004095 primary bone marrow fibrosis (PMF) is a bone marrow-promoting tumor (MPN) that can lead to bone marrow (BM) sexual fibrosis.
although cell mutations involved in the pathogenesis of PMF have been extensively studied, the sequence of events of drive substation activation and fibrosis through hematogenesis-substring crosslinking remains unclear.
tested by non-biased methods and in MPN patients, the researchers identified spatial differences in the expression of the cytokine CXCL4/plate plate platea factor 4 (PF4) to mark the progress of fibrosis.
Hematocyte CXCL4 deficiency improves MPN ideotypes, reduces substring cell activation and BM fibrosis, and reduces the activation of 3 PMF mouse models: 1) cytocytosis-promoting fibrosis path, 2) fibrosis drives cell inflammation, and 3) JAK/STAT activation of cytocytes and substylular cells.
5: Macrophages low phagocytorapy mediated mAb induced cell removal immune tolerance https://doi.org/10.1182/blood.2020005 571 macrophage antibody-dependent cellular phagocytosis (ADCP) is the primary cytotoxic mechanism for therapeutic monoclonal antibodies (mAb, such as lyxident) and antibody-induced hemolytic anemia and immunoplate reduction.
recently, researchers examined mechanisms to regulate the rate and ability of macrophages to perform ADCP at high target-effect cell ratios, such as circulating tumor loads in leukemia patients.
Through quantitative live cell imaging of macrophages in primary human patients and mice, the researchers found that after initially being stimulated by mAb-conditioning lymphocytes, macrophages experienced a brief rapid phagocytoste outbreak (-lt;1 hour), followed by a sharp decline in phagocytos activity that lasted several days.
AdCP's previously ambiguous period, or "hypophagia", was observed in kupffer cells in mice undergoing continuous alpha CD20 mAb-dependent circulatory B cells in all macrophages/mAb/target cells in vitro test conditions.
, hypophagia has no effect on antibody-dependent phagocytos and does not alter the viability of macrophages.
mechanism study, the study found that rapid loss of Fc subjects activated on the surface of macrophages and subsequent protein degradation were the main mechanisms for the loss of ADCP activity in hypophagia.
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