ARTICLES IN THREE SENTENCES
Co-targeting BCL-XL and BCL-2 by PROTAC 753B eliminates leukemia cells and enhances efficacy of chemotherapy by targeting senescent cells
Both BCL-2 and BCL-XL are validated therapeutic targets in a wide range of hematologic cancers, including acute myeloid leukemia. Moreover, BCL-XL is a mediator of chemo- and venetoclax-resistance. The first-in-class dual BCL-XL/BCL-2 proteolysis-targeting chimera (PROTAC) 753B selectively induces both BCL-XL and BCL-2 ubiquitination and degradation in cells expressing von Hippel-Landau (VHL). In their study, Jia and colleagues demonstrate that 753B effectively eliminates leukemia cells in vitro and in vivo, and enhances chemotherapy efficacy by targeting senescent cells.
Inactivation of p53 provides a competitive advantage to del(5q) myelodysplastic syndrome hematopoietic stem cells during inflammation
Hemizygous deletion of the long arm of chromosome 5q (del(5q)) is the most common cytogenetic alteration in myelodysplastic syndromes (MDS). The effects of low-grade inflammatory signals on hematopoietic stem and progenitorcells (HPSC) and del(5q) MDS progression remains uncharacterized. In their study, Muto and colleagues, using a mouse model, show that low-grade inflammation suppresses del(5q) MDS HSPC via p53, providing a potential explanation for the high grade of TP53 mutations in patients with del(5q) MDS.
Platelet phosphatidylserine is the critical mediator of thrombosis in heparin-induced thrombocytopenia
Heparin-induced thrombocytopenia (HIT) is a severe immune-mediated prothrombotic disease. The exact prothrombotic role of different platelet (PLT) subpopulations and the mechanism of their interaction with immune cells in HIT is poorly understood. In their study, Zlamal and colleagues demonstrate that procoagulant PLT, characterized by phosphatidylserine (PS) externalization, are critical mediators of prothrombotic conditions in HIT, and that PS blockade may prevent procoagulant PLT-mediated thrombus formation.
Real-world study of the efficacy and safety of belantamab mafodotin (GSK2857916) in relapsed or refractory multiple myeloma based on data from the nominative ATU in France: the IFM 2020-04 study
Treatment of multiple myeloma patients relapsed/refractory after immunomodulatory drugs, proteasome inhibitors and anti-CD38 monoclonal antibodies (mAb) represents a clinical challenge. Belantamab mafodotin, a first-in-class IgG1 humanized anti-BCMA (B-cell maturation antigen) mAb conjugated with a cytotoxic agent, is an efficacious alternative therapeutic option in this setting. Talbot and colleagues conducted a real-world retrospective study which confirmed study efficacy and safety data of the DREAMM-2 on a non-biased population.
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