May, 2023

No. 108 (5)

2021 CiteScore: 11.8 2021 Impact Factor: 11.04



Targeting a thrombopoietin-independent strategy in the discovery of a novel inducer of megakaryocytopoiesis, DMAG, for the treatment of thrombocytopenia

Thrombopoietin-receptor agonists do not always increase the number of platelets and have side effects. Moreover, they are are always ineffective in subjects with genetic defects of thrombopoietin receptor. Wang and colleagues developed a drug-screening model by the multi-grained cascade forest (gcForest) algorithm to look for a novel thrombopoietin-independent mechanism involving thrombopoiesis and potential druggable targets. They found that 3,8-di-O-methylellagic acid 2-O-glucoside (DMAG) promoted megakaryocyte differentiation and platelet formation in mice with thrombocytopenia.

Long Wang et al.


B- and T-cell acute lymphoblastic leukemias evade chemotherapy at distinct sites in the bone marrow

Persistence of measurable residual disease (MRD) under chemotherapy is a strong predictor of relapse of acute lymphoblastic leukemias (ALL) but the underlying mechanisms that enable cells to escape treatment are still unclear. Barz and colleagues used a three-dimensional fluorescence imaging to identify sites of predilection in the bone marrow for resistance to induction chemotherapy. They showed that the localization of human B-cell precursor ALL cells is not random with respect to other bone marrow structures and is distinct from the localization of T-ALL, indicating important functional differences between the two ALL lineage subtypes.

Malwine J. Barz et al.


Duality of Nrf2 in iron-overload cardiomyopathy

Federti and colleagues investigated nuclear erythroid factor-2 knockout (Nrf2-/-) mice and Hbbth3/+ mice model of β-thalassemia intermedia. They found novel evidence linking overactivation of the unfolded protein response system with hypertrophic cardiomyopathy in both iron overloaded Nrf2-/- mice and Hbbth3/+ mice. These findings open new perspectives in the understanding and treatment of cardiomyopathy in patients with b-thalassemia.

Enrica Federti et al.


Pirtobrutinib results in reversible platelet dysfunction compared to ibrutinib and acalabrutinib

Pirtobrutinib is a non-covalent oral Bruton tyrosine kinase inhibitor (BTKi) with high selectivity for BTK, impressive clinical activity and reduced risk for off-target toxicities, above all bleeding complications. In order to establish whether the lower rates of bleeding reported in pirtobrutinib trials corresponded with milder platelet dysfunction relative to covalent BTKi ibrutinib and acalabrutinib, Alexander and colleagues investigated platelet function in patients receiving treatment with covalent and non-covalent BTKi. Their findings suggest that rapid reversibility in platelet function rather than reduced platelet dysfunction might play a role in the low rates of hemorrhagic adverse events with pirtobrutinib.

Alexander P. Bye et al.