Take stock: A selection of Blod research on November 19, 2020

RunX1 and CBF beta-SMMHC common trans-activation abnormalities are consistent with leukemia https://doi.org/10.1182/blood.20200074716 chromosome inverted M4 subtype acute myeloid leukemia with acidoblastoid dystrophy (AML M4Eo) patients, which produces the CBFB-MYH11 fusion gene.
the fusion protein CBF beta-SMMHC, encoded by the CBFB-MYH11 fusion gene, is generally considered to be a significant negative inhibitor of RUNX1, researchers recently discovered a new pattern of effect.
to clarify the role of Runx1 in CBFB-MYH11-induced leukemia, the researchers interbred mice with conditioned knock-out of the Runx1 gene (Runx1f/f) with conditional Cfb-MYH11 knock-in mice (Cbfb plus/56M).
Mx1-Cre, injected by Poly (I:C, pIpC) to induce hematocytes, all of the Mx1-CreCbfb-56M mice developed leukemia within 5 months, while the Runx1f/fMx1-CreCbfb-plus/56M mice did not develop leukemia, and the effect was cellular autonomy.
importantly, in Runx1f/fMx1-CreCbfb-plus/56M mice, the Cbfb-MYH11-induced leukemia starting cell group, the abnormal myelin ancestral cells (AMPs), decreased or even disappeared.
RNA-seq analysis of AMP cells showed that Mx1-CreCbfb plus 56M and Runx1f/fMx1-CreCbfb plus/56M mice had differential expression of genes associated with the onset of leukemia.
addition, by chromosomal immunocute sequencing (ChIC-seq), the researchers observed that the RUNX1/CBF beta-SMMHC target gene was significantly rich in Runx1f/fMx1-CreCbfb-56m cells, especially in the downgraded gene, suggesting that RUNX1 and CBF beta-SMMHC act together to activate gene expression primarily by directly binding the target gene.
. AFM13 combined with Pam single anti-treatment recurring/refractic Hodgkin's lymphoma https://doi.org/10.1182/blood.2019004701 In recurring/refractic Hodgkin's lymphoma (R/R HL), immunotherapy (e.g., PD-1 inhibitor Pym single resistance) plays an increasingly important role in treatment.
CD30/CD16A dual-specific antibody AFM13 is a congenital immunocellular joint, is a first-class teutocyte antibody, designed to build a bridge between CD30 on HL cells and CD16A subjects on NK cells and macrophages to induce tumor cell destruction.
earlier studies of AFM13 showed that AFM13 monotherapy was available in patients with R/R HL, and that the joint approach between AFM13 and Pim monoantigen represented a reasonable new treatment.
researchers recently reported the results of an incremental phase 1b dose study evaluating patients with AFM13 combined with Pym monoantigen therapy R/R HL.
main purpose is to identify the maximum to-dosage (MTD), and the secondary objective is to assess the safety, toerability, anti-tumor activity, pharmacodynamics and pharmacoetics of the joint programme.
in patients who have been treated multiple times in the past, AFM13 combined with Pym monoantigen is generally better and has similar safety characteristics compared to the known characteristics used separately for each drug.
the maximum therapeutic dose, the objective mitigation rate of AFM13 combined Pym monoantigen reached 88% and the overall remission rate was 83%.
in this combined treatment, AFM13's pharmacodynamic assessment showed a half-life of up to 20.6 hours.
. BET inhibitor CPI203 promotes cord blood HSC and macrophage amplification https://doi.org/10.1182/blood.2020005357 Although cytokine-mediated artificial blood stem cell (HSCs) amplification can lead to high yield of hematopoietic ancestral cells, this is usually at the expense of reducing the regenerative capacity of myeloid stem cells, thus limiting the potential therapeutic value.
Given that proteins (BCPs) containing Bromodomain have been shown to regulate the self-renewal and resting state of HSC in mice, the researchers screened small molecules targeting various BCPs as potential reagents for introplification of artificial blood stem cells.
of the 10 tested compounds, only the bromine region domain and BET (Extra-terminal module) inhibitor CPI203 can enhance the in vitro amplification of human umbilical cord blood HSC without loss of cellular vitality.
in a series of transplant trials, amplification cells have also been shown to improve transplantation and regeneration.
transcription group and functional studies have shown that the amplification of long-term regenerative HSC is accompanied by the simultaneous amplification and maturation of giant nucleocytes, which is consistent with the reprogramming of umbilical hematocytes/pregenital cells (HSPCs) mediated by CPI203.
: Immune synapses HLA-II and CD58 activate rose knot T cell DOI: 10.1182/blood.2020005546 Hodgkin's lymphoma (HL) is a unique feature that surrounds tumor cells around CD4 plus T cells to protect and promote tumor cell survival.
the adhesive molecule involved in this so-called T-cell rose knot is an important part of immune synapses (IS).
, however, it is not clear whether the synapse is fully assembled, which causes T-cell activation by interacting with human type II white blood cell antigens (HLA-II).
researchers recently created a new rose knot model by co-cultured HLA-II-matched PBMCs and HL cell line, and demonstrated the formation of IS by activating rose knot T cells.
the reduction of HLA-II through CIITA did not affect the degree of rose knots, but almost completely abolished T-cellization.
interestingly, CD58's expression level is associated with the degree of formation of the rose knot, and knocking out CD58 or blocking CD2 can reduce the formation of the rose knot and T-cell biopic.
the above findings were extended to primary HL tissue through immunohistification and adjacent nosal analysis, and the results showed that CD2 interacted with CD58 and TCR-related CD4 interacted with HLA-II.
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