Review Series On Treatment Of Thrombocytopenias
Introduction to a review series on the treatment of thrombocytopenic disorders: something old, something new
ARTICLES IN THREE SENTENCES
Either IL-7 activation of JAK-STAT or BEZ inhibition of PI3K-AKT-mTOR pathways dominates the single-cell phosphosignature of ex vivo treated pediatric T-cell acute lymphoblastic leukemia cells
Targeted therapy for T-ALL is urgently needed, together with precision medicine diagnostic tools. Kuzilková et al used single-cell mass cytometry to study signal transduction pathways in T-ALL primary samples, and investigated the in vitro response of cells to IL-7 and the inhibitor BEZ-235. They identified distinct clusters with different responsiveness to IL-7 and BEZ-235 that can persist at relapse. These data contribute to a better understanding of the complex signaling network governing T-ALL behavior and its correlation with influence on the response to therapy.
Apoptosis reprogramming triggered by splicing inhibitors sensitizes multiple myeloma cells to Venetoclax treatment
RNA splicing deregulation represents an innovative and exciting area of research, and a novel target for anticancer therapy. Soncini et al evaluated the expression of several spliceosome machinery components in MM cells and the impact of splicing modulation on tumor cell growth and viability. They confirmed that alternative splicing is largely perturbed in MM cells and demonstrated that low dose of splicing modulators, by shifting apoptotic dependencies, results in enhanced BH3 mimetic Venetoclax susceptibility.
Isatuximab plus carfilzomib and dexamethasone versus carfilzomib and dexamethasone in relapsed multiple myeloma patients with renal impairment: IKEMA subgroup analysis
The phase III IKEMA study (NCT03275285) investigated isatuximab with carfilzomib and dexamethasone (Kd) versus Kd in relapsed MM. Capra and colleagues presented a subgroup analysis that examined results from patients with renal impairment. The addition of Isatuximab to Kd improved clinical outcomes with a manageable safety profile in patients with renal impairment.
The currently approved monoclonal antibodies eculizumab and ravulizumab significantly reduce intravascular hemolysis and transfusion dependency and improve the life expectancy of PNH patients, however, there are several patients who do not respond due to a variant C5 protein. Nishimura et al showed the results of the open-label, single-arm, multicenter, proof-of-concept phase II trial conducted to test the efficacy of tesidolumab in patients with variant and non-variant C5. In summary, tesidolumab had a favorable safety profile and was efficacious for PNH patients with either variant or nonvariant C5.
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