Targeting Apoptosis in ALL

AbstractPurpose of ReviewWhile the treatment of acute lymphoblastic leukemia (ALL) has improved significantly over the last 30  years, the majority of adult patients will have their disease relapse. TheBCL-2 gene was initially discovered from follicular lymphoma research; however, the BH3 family of proteins has is emerging to be crucial in patients with ALL due to their reliance on the balance of these pro-apoptotic and anti-apoptotic proteins in the BH3 family. We discuss apoptosis in ALL, the reliance mechanisms, drug development in this space, and areas for future research.Recent FindingsThe first drugs that were developed to inhibit the BCL-2 pathway include both venetoclax (BCL-2 specific inhibitor) and navitoclax (BCL-2, BCL-XL, and BCL-W). These drugs show promise and have obtained complete remissions, minimal residual disease negative status, and have been used as a bridge to allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia and chronic lymphocytic leukemia. There are multiple ongoing clinical trials looking to assess the use of BCL-2 inhibition with chemotherapy, targeted therapies, and bi-specific T-cell engager therapies not only in both frontline and relapsed refractory ALL but also in consolidation and maintenance phases.SummaryThere is still a large need for improvement of ALL outcomes in adult patients. Research has shown that ALL depends on the BCL-2 family of proteins for cell survival and proliferation. Targeting this pathway with...
Source: Current Hematologic Malignancy Reports - Category: Hematology Source Type: research