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http://dx.doi.org/10.1016/j.gie.2023.03.027 | DOI Listing |
Blood
March 2025
Sanofi, Cambridge, Massachusetts, United States.
Rilzabrutinib is a covalent, reversible BTK inhibitor with multiple mechanisms targeting key immune thrombocytopenia (ITP) disease pathophysiology. The phase 3 LUNA3 study in previously treated adults with persistent/chronic ITP evaluated oral rilzabrutinib 400 mg bid (n=133) vs placebo (n=69) for 24 weeks. At baseline overall, median age was 47 years (range, 18-80), 63% female, 7.
View Article and Find Full Text PDFThe CREBBP lysine acetyltransferase (KAT) is frequently mutated in follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) and has been studied using gene knock-out (KO) in murine and human cells. However, the majority of CREBBP mutations encode amino acid substitutions within the catalytic KAT domain (CREBBP KAT-PM) that retain an inactive protein and have not been extensively characterized. Using CRISPR gene editing and extensive epigenomic characterization of lymphoma cell-lines, we found that CREBBP KAT-PM lead to unloading of CREBBP from chromatin, loss of enhancer acetylation and prevention of EP300 compensation.
View Article and Find Full Text PDFBlood
March 2025
Washington University School of Medicine, St. Louis, Missouri, United States.
Cytokine release syndrome (CRS) and immune effector cell (IEC)-associated neurotoxicity syndrome (ICANS) are common complications following IEC therapy for hematologic malignancies. This two-part, phase 2 study (INCB 39110-211) investigated safety and efficacy of itacitinib, a potent, highly selective Janus kinase 1 inhibitor with broad anti-inflammatory activity, for prevention of CRS and ICANS in patients receiving commercial CD19-directed IEC therapy. Patients in part 1 received once-daily itacitinib 200 mg 3 days before IEC therapy (axicabtagene ciloleucel [axi-cel], brexucabtagene autoleucel, or tisagenlecleucel) through Day 26, with guidelines for use of other CRS/ICANS interventions.
View Article and Find Full Text PDFBlood
March 2025
the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome, and the overall survival of adult patients is poor. Ruxolitinib, a Janus kinase (JAK) 1/2 inhibitor, has shown promise in treating HLH and exerts synergistic effects when combined with dexamethasone. Our pilot study preliminarily demonstrated that the combination of ruxolitinib and dexamethasone (the Ru-D regimen) had a high response rate and led to favorable short-term survival outcomes in adult HLH patients.
View Article and Find Full Text PDFBlood
March 2025
UC San Diego, La Jolla, California, United States.
Inherited bone marrow failure syndromes (IBMFS) are genetic disorders of impaired hematopoiesis that manifest in childhood with both cytopenias and extra-hematologic findings. While several IBMFS are categorized as ribosomopathies due to shared underlying ribosomal dysfunction, there is a broader disruption of the protein homeostasis (proteostasis) network across both classic and emerging IBMFS. Precise regulation of the proteostasis network, including mechanisms of protein synthesis, folding, trafficking, and degradation as well as associated stress response pathways, has emerged as essential for maintaining hematopoietic stem cell (HSC) function, providing new potential mechanistic insights into IBMFS pathogenesis.
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