A selection of Blod research on November 26, 2020

1. Kafazomi-Lenadamine-Desamisong joint stem cell transplantation treatment for multiple myeloma https://doi.org/10.1182/blood.2020007522 in multi-center Phase II study (NCT01816971), the researchers evaluated the efficacy of the self-stem cell transplant (ASCT) joint carphetamine-desamisson (KRd) program in newly diagnosed patients with multiple myeloma (NDMM).
NDMM patients, KRd was given 4 courses of KRd induction-ASCT-4 courses of KRd consolidation, and 10 courses of KRd were maintained.
end point of the treatment is a strict full remission (sCR) rate after 8 KRd sessions.
76 patients were involved in the trial, with a medium age of 59 (40-76 years) and 35.5 percent having high-risk cytogenetics.
the results reached the main endpoint, with a sCR rate of 60% after eight courses.
and the depth of mitigation deepens over time.
the sCR rate was 76% among the intent therapy (ITT) population.
, the MRD negative rate assessed using second-generation sequencing was 70%, according to the correctEDT. After 56 months of
-medium follow-up, the five-year progressive survival rate (PFS) and overall survival rate (OS) in the ITT population were 72% and 84%, respectively, PFS and OS were 85% and 91% in MRD-negative patients, 57% and 72% in high-risk cytogenetics patients, and 77% and 81% respectively in high-risk patients with MRD negative.
3/4 adverse reactions included a reduction in neutral granulocytes (34%), a decrease in lymphocytes (32%), infections (22%) and cardiovascular events (3%).
no 3/4 levels of peripheral neuropathy.
. The active https://doi.org/10.1182/blood.2020005683 gene therapy based on adeno-related virus (AAV) can restore the expression of the endogenetic factor VIII (FVIII) of haemophilia A (HA) in human plasma after AAV5 gene therapy.
AAV vectors typically utilize FVIII transgenics missing from the B domain, such as the human FVIII-SQ in the valoccogene roxparvovec (AAV5-FVIII-SQ).
, the activity of FVIII-SQ produced by GM in stage I blood clots (OS) was 1.3-2.0 times higher than that of hair color substrates (CS), while the OS activity of recombinant FVIII-SQ was lower than CS.
in CS experiments, GM FVIII-SQ had similar specific activity (IU/mg) with recombinant FVIII-SQ, indicating that different activities appeared in OS experiments.
high OS activity of FVIII-SQ produced by GM was observed in different test kits and clinical laboratories, indicating that the underlying molecular characteristics were the underlying cause.
further experiments in two subjects showed that FVIII-SQ produced by GM accelerated the formation of early factors Xa and clotting enzymes, which may explain the higher OS activity based on the dynamic deviation between OS and CS detection read time.
although clotting began faster, the overall level of clotting enzymes was not affected.
correlation between blood and joint bleeding shows that OS and CS testing are still clinically significant in distinguishing between haemophilia and non-haemophilia FVIII activity levels.
. RET activation and survival and amplification of hematopoietic stem cells https://doi.org/10.1182/blood.2020006302 In vitro culture amplification is a rapidly developing field, showing great hope for clinical applications.
recent studies have shown that nervous system and glial family ligation (GFL) are potential drivers of blood survival and self-renewal in bone marrow niches, but how to apply them to the maintenance and amplification of HSC remains to be seen.
researchers recently revealed the role of GFL-subject RET on the surface of HSCs cells in mediating continuous cell growth, resistance to stress and improved cell survival throughout the in vitro amplification process.
treatment of HSCs with the RET complex GDNF/GFRa1 improves the function of the ancestral cells at the time of the initial transplant and the long-term function of the HSC during the second transplant.
study confirms that RET drives multiple in-cell signaling paths, including key signaling members AKT, ERK1/2, NF-B, and p53, responsible for a wide range of cellular and genetic responses that improve cell growth and survival in in vitro culture.
MIF and Protease inhibitor resistance in patients with multiple myeloma https://doi.org/10.1182/blood.2020005795 Despite significant advances in biology and chemotherapy, multiple myeloma (MM) remains largely incurable.
main problem in MM management is the production of drug resistance.
study found that macrophage migration inhibitors (MIF) were significantly expressed in purified MM cells from relapsed patients, and that progression-free survival (PFS) and overall survival (OS) were significantly shorter in MIF-expressed MM patients.
MM cell line also expresses a high level of MIF, knocking out MIF can make the MM cell line sensitive to apoptosis induced by protease inhibitor (PI) and has no effect on the therapeutic effect of other chemotherapy.
mechanism studies have shown that MIF can maintain mitochondrial function by inhibiting the production of peroxides during PI treatment, thereby protecting MM cells from PI-induced apoptosis.
specifically, MIF, which exists in pure trimer form, acts as a molecular companion to superoxide dismishing enzyme 1 (SOD1), inhibits PI-induced SOD1 misfolding and maintains SOD1 activity.
MIF inhibitor 4-IPP and pure trimer destroyer ebselen do not kill MM cells, but can enhance PI-induced SOD1 misfolding and loss of function, which significantly increases MM cell line and primary MM cell death.
, inhibiting MIF activity in the body exhibits co-anti-tumor activity with PI and makes PI drug-resistant MM cells resensitive to PI therapy.
gene spectrometum data showed that the expression of MF/SOD1 was significantly negatively related to the response of MM patients to PI treatment.
-β catenin-TCF/LEF signal promotes granulocyte differentiation by raising the G-CSF subject to https://doi.org/10.1182/blood.2019004664 Classic Wnt signal path is regulated by the interaction between β-catenin and TCF/LEF transcription factor, and the Wnt gene is subsequently activated.
in hematic systems, the function of this path is mainly studied through the nonsexual genetic operation of β-catenin, but often with contradictory results.
recently, researchers used mice expressing human TCF4 transcription factor truncation of the explicit negative form (dnTCF4) to study the role of β-catenin-TCF/LEF interactions in hematogic systems, and the mouse model's β-catenin-TCF/LEF interactions were disrupted.
β-catenin-TCF/LEF interactions are disrupted leading to the accumulation of immature blood cells and reduced granulocyte differentiation.
the mechanism, the Csf3r gene of dnTCF4 ancestral cells was reduced, the level of G-CSF subjects decreased, the phosphate of downstream Stat3 decreased after G-CSF treatment, and the differentiation of G-CSF-mediated was impaired.
chromosomal immunopopulation experiments showed that TCF/LEF factors were directly combined with the initiators of CSF3R and the presumed enhanced subregions.
inhibition β-catenin signal can impair the activation of the acute production process of granulocytes, which require the maintenance and amplification of myelin ancestral cells.
, dnTCF4 mice were susceptible to white Candice and were more sensitive to 5-fluorouracil-induced granulocyte regeneration.
important, genetically and chemically inhibiting the β-catenin-TCF/LEF signal of human CD34 plus cells reduces granulocyte differentiation, and activation of this signal enhances granulocyte production.
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