Metabolic control of epigenetic rearrangements in B cell pathophysiology.

Both epigenetic and metabolic reprogramming guide lymphocyte differentiation and can be linked, in that metabolic inputs can be integrated into the epigenome to inform cell fate decisions. This framework has been thoroughly investigated in several pathophysiological contexts, including haematopoietic cell differentiation. In fact, metabolite availability dictates chromatin architecture and lymphocyte specification, a multi-step process where haematopoietic stem cells become terminally differentiated lymphocytes (effector or memory) to mount the adaptive immune response.

CX-4945, a Selective Inhibitor of Casein Kinase 2, Synergizes with B Cell Receptor Signaling Inhibitors in Inducing Diffuse Large B Cell Lymphoma Cell Death.

Background: Approximately one third of Diffuse Large B cell Lymphomas (DLBCL) are refractory or relapse. Novel therapeutic approaches under scrutiny include inhibitors of B-cell receptor (BCR) signaling. Protein kinase CK2 propels survival, proliferation and stress response in solid and hematologic malignancies and promotes a "non-oncogene addiction" phenotype.

Inactivation of CK1α in multiple myeloma empowers drug cytotoxicity by affecting AKT and β-catenin survival signaling pathways.

Recent evidence indicates that protein kinase CK1α may support the growth of multiple myeloma (MM) plasma cells. Here, by analyzing a large cohort of MM cases, we found that high CK1α mRNA levels are virtually associated with all MM patients. Moreover, we provided functional evidence that CK1α activity is essential for malignant plasma cell survival even in the protective niche generated by co-cultures with bone marrow stromal cells.

Glycogen Synthase Kinase-3 regulates multiple myeloma cell growth and bortezomib-induced cell death.

Background: Glycogen Synthase Kinase-3 (GSK-3) α and β are two serine-threonine kinases controlling insulin, Wnt/β-catenin, NF-κB signaling and other cancer-associated transduction pathways. Recent evidence suggests that GSK-3 could function as growth-promoting kinases, especially in malignant cells. In this study, we have investigated GSK-3α and GSK-3β function in multiple myeloma (MM).