In Vitro and In Vivo Models of CLL-T Cell Interactions: Implications for Drug Testing - PubMed
Source : https://pubmed.ncbi.nlm.nih.gov/35804862/
T cells are key components in environments that support chronic lymphocytic leukemia (CLL), activating CLL-cell proliferation and survival. Here, we review in vitro and in vivo model systems that mimic...
Relevance: We discuss approaches for direct CLL-cell co-culture with autologous T cells, models utilizing supportive cell lines engineered to express T-cell factors (such as CD40L) or stimulating CLL cells with combinations of recombinant factors (CD40L, interleukins IL4 or IL21, INFγ) and additional B-cell receptor (BCR) activation with...
Tumor Microenvironment and Immunotherapy-Based Approaches in Mantle Cell Lymphoma - PubMed
Source : https://pubmed.ncbi.nlm.nih.gov/35804999/
1 Department of Hematology, Gustave Roussy Cancer Campus, 94805 Villejuif, France. 2 Department of Hematology, Necker Hospital, Assistance Publique des Hopitaux de Paris (APHP), 75004 Paris, France. 3 Nantes Universite,...
Relevance: Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma (NHL) characterized by the translocation t(11;14) (q13;q32) and a poor response to rituximab-anthracycline-based chemotherapy. High-dose cytarabine-based regimens offer a durable response, but an important number of MCL patients are not eligible for intensive...
Mechanisms of resistance to noncovalent Bruton's tyrosine kinase inhibitors | Mission Bio
Source : https://missionbio.com/resources/publications/wang-nejm-2022/
Covalent (irreversible) Bruton's tyrosine kinase (BTK) inhibitors have transformed the treatment of multiple B-cell cancers, especially chronic lymphocytic leukemia (CLL). However, resistance can arise through multiple mechanisms, including acquired mutations...
Conclusions: Resistance to noncovalent BTK inhibitors arose through on-target BTK mutations and downstream PLCγ2 mutations that allowed escape from BTK inhibition. A proportion of these mutations also conferred resistance across clinically approved covalent BTK inhibitors. These data suggested new mechanisms of genomic escape from established...
A Novel Triple-Action Inhibitor Targeting B-Cell Receptor Signaling and BRD4 Demonstrates Preclinical Activity in Chronic Lymphocytic Leukemia - PubMed
Source : https://pubmed.ncbi.nlm.nih.gov/35743155/
B-cell chronic lymphocytic leukemia (CLL) results from intrinsic genetic defects and complex microenvironment stimuli that fuel CLL cell growth through an array of survival signaling pathways. Novel small-molecule agents targeting...
Zanubrutinib in Treating Waldenström Macroglobulinemia | TCRM
B-cell development, survival, and expansion is critically dependent on normally functioning and tightly regulated B-cell receptor (BCR) signaling pathways. Key mediators of the BCR pathway include the proximal kinases -...
Conclusion: Even though zanubrutinib has been the third and last BTK inhibitor to currently penetrate the market for B-cell lymphoproliferative malignancies, we highlight the emergence of zanubrutinib as a key player in the forefront of the therapeutic landscape in WM.