The clinical efficacy of proteasome inhibitors in the treatment of multiple myeloma has encouraged application of proteasome inhibitor containing therapeutic interventions in (pediatric) acute leukemia. Here, we summarize the positioning of bortezomib, as first-generation proteasome inhibitor, and second-generation proteasome inhibitors in leukemia treatment from a preclinical and clinical perspective. Potential markers for proteasome inhibitor sensitivity and/or resistance emerging from leukemia cell line models and clinical sample studies will be discussed focusing on the role of immunoproteasome and constitutive proteasome (subunit) expression, PSMB5 mutations, and alternative mechanisms of overcoming proteolytic stress.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5721123 | PMC |
| http://dx.doi.org/10.1007/s10555-017-9699-4 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Successful treatment with bortezomib for refractory cryoglobulinemic vasculitis triggered by ischemic non-obstructive coronary artery disease.
CEN Case Rep
January 2025
Department of Nephrology and Dialysis, Tokyo Metropolitan Institute for Geriatrics and Gerontology, 35-2 Sakae-Cho, Itabashi, Tokyo, 173-0015, Japan.
Type I and mixed cryoglobulinemic vasculitis differ in pathophysiology, clinical presentation, and therapeutic response. We report a case of refractory cryoglobulinemic vasculitis diagnosed following ischemic non-obstructive coronary artery disease (INOCA). The patient presented with dyspnea, as well as abdominal pain due to ischemic enteritis, purpura, and renal failure requiring dialysis.
View Article and Find Full Text PDFInvolvement of the ubiquitin-proteasome system in the regulation of the tumor microenvironment and progression.
Genes Dis
March 2025
Department of Pathophysiology, College of High Altitude Military Medicine, Army Medical University, Chongqing 400038, China.
The tumor microenvironment is a complex environment comprising tumor cells, non-tumor cells, and other critical non-cellular components. Some studies about tumor microenvironment have recently achieved remarkable progress in tumor treatment. As a substantial part of post-translational protein modification, ubiquitination is a crucial player in maintaining protein stability in cell signaling, cell growth, and a series of cellular life activities, which are also essential for regulating tumor cells or other non-tumor cells in the tumor microenvironment.
View Article and Find Full Text PDFInhibition of proteolytic and ATPase activities of the proteasome by the BTK inhibitor CGI-1746.
iScience
November 2024
Department of Drug Discovery and Development, Harrison College of Pharmacy, Auburn University, 720 S. Donahue Dr., Auburn, AL, USA.
Bruton's tyrosine kinase (BTK) inhibitor, ibrutinib, has been shown to synergize with proteasome inhibitors (PIs) in reducing the viability of cells derived from B cell malignancies, but the mechanism is not known. We report here that an off-target effect of ibrutinib causes synergy because not all BTK inhibitors exhibited the synergistic effect, and those that synergized did so even in cells that do not express BTK. The allosteric BTK inhibitor CGI-1746 showed the strongest synergy.
View Article and Find Full Text PDFBoanmycin overcomes bortezomib resistance by inducing DNA damage and endoplasmic reticulum functional impairment in multiple myeloma.
Biol Direct
January 2025
Department of Hematology, The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People's Hospital of Shenzhen, Shenzhen, 518172, China.
Background: Multiple myeloma (MM) is a hematological malignancy characterized by uncontrolled proliferation of plasma cells and is currently incurable. Despite advancements in therapeutic strategies, resistance to proteasome inhibitors, particularly bortezomib (BTZ), poses a substantial challenge to disease management. This study aimed to explore the efficacy of boanmycin, a novel antitumor antibiotic, in overcoming resistance to BTZ in MM.
View Article and Find Full Text PDFPatient-reported outcomes following ciltacabtagene autoleucel or standard of care in patients with lenalidomide-refractory multiple myeloma (CARTITUDE-4): results from a randomised, open-label, phase 3 trial.
Lancet Haematol
January 2025
University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Background: In CARTITUDE-4, ciltacabtagene autoleucel (cilta-cel) significantly improved progression-free survival (primary endpoint; previously reported) versus standard of care in patients with relapsed, lenalidomide-refractory multiple myeloma. We report here patient-reported outcomes.
Methods: In the ongoing, phase 3, open-label CARTITUDE-4 study, patients were recruited from 81 sites in the USA, Europe, Asia, and Australia, and were randomly assigned 1:1 to cilta-cel (target, 0·75 × 10 CAR-T cells/kg) or standard of care (daratumumab, pomalidomide, and dexamethasone; pomalidomide, bortezomib, and dexamethasone).
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!