A selection of Blod research on August 27, 2020.

1. Ipale Net corrects glycogen storage IB's neutral granulocyte reduction and its dysfunction https://doi.org/10.1182/blood.2019004465 Neutral granulocyte reduction and neutral granulocyte dysfunction can cause severe infection and inflammatory bowel disease in patients with GSD-Ib.
Recently, researchers found that in mouse models of G6PC3 defects and two rare diseases (GSD-Ib and G6PC30 deficiency), the accumulation of 1,5-waterless glucose-6-phosphoric acid led to a decrease in neutrogenic granulocytes, and therefore the widely used anti-diabetic drug Ipalein (a renal glucose co-transporter SGLT2 inhibitor) was used to treat GSD-Ib.
4 GSD-Ib patients treated with granulocyte-collecting stimulation factor (GCSF) did not receive complete remission, and serum 1,5-waterless glucose and neutral granulocytes 1,5-water-free glucose-6-phosphate levels decreased within one month of the use of Ipale net therapy.
clinically, frequent infections, mucosal lesions, inflammatory bowel disease symptoms disappeared, and there were no symptoms of hypoglycemia.
two patients were able to deactive GCSF, and the other two gradually reduced their use by 57% and 81%, respectively.
number of neutral granulocytes increased and stabilized in all patients.
researchers further confirmed that the function of neutral granulocytes in patients was also improved: normal oxidation outbreaks (3/3), corrected protein glycosylation (2/2), and normal neutral granulocyte generalization (1/1) and sterilization activity (1/1).
: New advances in red blood cell generation regulation mode https://doi.org/10.1182/blood.2019003276 erythymocytogen (Epo) provides the primary survival signal for mature red blood cell pregenes (EPs) and is essential for eventual red blood cell production.
Even so, the ancestral cells can irreversibly differentiate into the red line before Epo takes effect, but if they are not needed to maintain the red blood cell (RBC) count, they are wasted.
recently, researchers identified a new pattern of red blood cell production and demonstrated for the first time that the pre-Epo pattern is coupled with late Epo-dependent red blood cell generation through cytocytocyte signals.
Tgfb1, which destroys cytocytes, can cause hematosis by expanding the Epo pre-pool of the ancestral cells, triggering the apparent apoptosis of Epo-dependent red line pregeners.
, pharmacological blocking of TGF beta signals in normal mice enhanced Epo pre-patterns, leading to Epo sensitivity EP apoptosis.
subsequent treatment with low-dose Epo triggered mass production of RBC in both models.
.3 Molecular anatomy of immunogenitation defects in the embryoline TAT2 leads to childhood immunodeficiency and lymphoma https://doi.org/10.1182/blood.2020005844 Immune birth defects help clarify the non-redundant function of individual genes.
researchers recruited three children with immunodeficiform syndrome who showed susceptible to infection, lymph node disease, enlarged liver and spleen, stunted development, autoimmune and B-cell or T-cell-sourced lymphomas (2 bits of B-cells, 1 bit of T-cells).
all three children had early autobiographic T-cell reconstruction after the transplant of hematopoietic stem cells.
using all-exon sequencing, researchers found rare, pure, embryo-misalmed, or senseless variations in DNA hydroxymethylase TET2.
TET2 catalyzed 5-methyl cytosine (5mC) on RNA to form 5-hydroxymedase (5hmC), which plays an important role in opening up natural immune responses.
the mutant TET2 protein does not express or present 5-hydroxymethylation active enzymatic defects, leading to high methylation of blood DNA as a whole.
in two children, circulating T-cells exhibited abnormal immune esoploids, including double-negative cell amplification, bubble-assisted T-cell cavity failure, and fas-dependent apoptosis damage.
, the missing B cells of TET2 exhibit recombination defects like switch-like.
hematopoietic potential of induced erythmic stem cells from children with the disease is tilted toward myelin cells.
.4: Glucosticosterone enhances the anti-FLT3 mutant AML activity of FLT3 inhibitors https://doi.org/10.1182/blood.2019003124FLT3 is a gene with frequent mutations, closely related to the adverse prognostication of acute myeloid leukemia (AML).
most AML patients initially responded to FLT3 inhibitor treatment, they eventually relapsed due to drug resistance.
, the mechanism by which FLT3 inhibitors develop resistance and the initial response to drugs that promote cell survival is unclear.
recent studies have shown that a short-lived subpopulation of drug-sensitive cells, known as drug-resistant persistents (DTP), can survive cytotoxic drug exposure even in the absence of drug-resistant mutations.
through RNA sequencing and drug screening, Gebru and others found that the treatment of FLT3-ITD AML cells with the selective FLT3 inhibitor quizartinib increased the inflammatory gene of DTPs, thereby enhancing their sensitivity to anti-inflammatory glucoticoids.
In mechanism, the combined use of FLT3 inhibitors and glucosal hormones increases protease degradation of apoptosis protein BIM and anti-apoptosis protein MCL-1 through glucosal hormone-dependent subjects, thereby enhancing cell death in FLT3 mutant cells without affecting the survival of wild cells.
addition, the researchers confirmed an increase in antileukemia activity in the combined application of quezatinini and dexamisone in samples of primary AML patients and models of xeno-transplanted mice.
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