A selection of Blood Research On July 23, 2020.

1.!---- CDK6, NUP98 fusion protein and acute myeloid leukemia https://doi.org/10.1182/blood.2019003267 fusion proteins associated with nucleoporous protein 98 (NUP98) recur in acute myeloid leukemia (AML) and are associated with poor prognosisRecently, researchers have found that different NUP98 fusion proteins can relieve the regulation of a common set of transcription targets that can be used for targeted therapyIn the mouse model, the researchers defined the core set of the direct transcription target of nUP98 fusion protein by integrating the chromatin occupancy spectrum of NUP98 fusion proteins with the transcription alme sepsis of acute fusion proteins in vivoAmong them, CDK6 was highly expressed in mouse and human AML samplesCDK6 deficiency slows the occurrence of NUP98 fusion-driven leukemia, and NUP98 Fusion AML is sensitive to drug-suppressing CDK6, both in vivo and in vitroEGFR-dependent DNA repair promotes hematopoietic regeneration https://doi.org/10.1182/blood.202005895 chemotherapy and radiotherapy can cause DNA damage of hematopoiating stem cells (HSCs), leading to HSC depletion and dysfunction, and malignant transformation over timeRecently, researchers found that epidermal growth factor receptors (EGFR) regulate DNA repair of HSC by activating DNA-dependent protein kinase -catalytic sub-cells (DNA-PKcs) and non-homologoological end connections (NHEJ)Blood regeneration in the body after systemic radiotherapy (TBI) depends on the repair of DNA damage mediated by EGF by activating DNA-PKcsConditional knockout of EGFR in hematopoietic dry/progenitor cells (HSPC) significantly reduces the activity of DNA-PKcs after radiotherapy, resulting in increased HSC DNA damage and inhibition of HSC recoveryEGF promotes HSC DNA repair and rapid blood recovery in chemotherapy mice, with no effect on the growth of AML in the bodyIn addition, EGF therapy can promote the recovery of HSC in the body that can redifferentiate in multispectral humans after radiation damageGenome-wide sequencing analysis showed that the mutations in the coding area of HSPC in mice treated with EGF did not increase, but the number of copies between genes increasedThe high protein load of the 14-3-3 protein regulates MM's sensitivity to protease inhibitors https://doi.org/10.1182/blood.2019004147, which is one of the characteristics of multiple myeloma (MM), making the disease very sensitive to protease inhibitors (PI)The researchers, using the co-function of the recognized 14-3-3 protein, assessed their role in influencing protease activity and sensitivity to PI in MM cell lines by associating the expression of the individual's 14-3-3 gene and its sensitivity to PI (boratizomi and Kafizomi)The researchers observed a significant positive correlation between the expression of 14-3-3 thin and the PI responseThe researchers observed that 14-3-3 sh) promotes phosphorylation by binding inhibition of the TSC1/TSC2 complex and interacts directly with mTORC1, playing a positive role in facilitating the translation initiation of MM cells and protein synthesisDepletion of 14-3-3 thin can lead to a 50% reduction in protein synthesis, including reduced abundance and light chain secretion within MM cells, while overexpression in KO cells or the addition of 14-3-3 thin can lead to significant increases in protein synthesis and protein load Importantly, the correlation between 14-3-3-3 expression and PI sensitivity and protein load was observed in both progenitor MM cells from two independent data sets, and the low expression was associated with poor prognosis in MM patients treated with boron-tatizomi A small number of T cells that identify tumor-related antigens can stimulate anti-tumor response https://doi.org/10.1182/blood.2019004443 tumor-related antigen (TAA) is a monomorphic autogen that is considered an immunotherapy target for malignant tumors Recently, researchers used secondary tissue compatibility antigen (MIHA)-specific T cells as a model to study the differences between the t-cell lineage of thymus selection against MiHA in the context of itself (MiHApos donor) and non-self (MiHAneg donor) donor Isolated the targeted HLA-02:01-1HHA HA-1HHh t-cell cloning from the HA-1Hneg/HLA-A-A-02-01pos donor Of the 16 HA-1H-specific T-cell clones, 5 were from HA-1Hneg/HLA-A-02:01pos donors and 1 T-cell clone from the HA-1Hpos/HLA-A-A-02:01pos donor showed resistance to HA-1Hpos target cells In addition, 663 T-cell clones targeting TAA WT1-RMF, RHAMM-ILs, Proteinase-3-VLQ, PRAME-VLD and NY-ESO-1-SLL are isolated from HLA-A?02:01-01 restrictive polypeptideclones (including at least 91 unique clones expressing different T-cell clones) Only 3 PRAME-VLD and 1 NY-ESO-1-SLL-specific T cell clone selicing in HLA-A-02:02:01pos malignant cell line (not the original malignant specimen) naturally over-expression of TAA stimulation, can induce ifN-iso-production and/or cell dissolution Source: MedSci Original !-- Content Presentation Ends - 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