Progress of B Cell Lymphoma 2 Inhibitors in the Treatment of Myelodysplastic Syndrome

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell disorders. Despite significant progress in the genetic heterogeneity of myelodysplastic syndrome (MDS), novel and effective therapies for MDS have lagged behind that of many other malignancies. Preclinical studies have demonstrated that B cell lymphoma-2(BCL-2) is overexpressed in high-risk MDS, and BCL-2 inhibition induces apoptosis in MDS progenitor cells. BCL-2 inhibitor has undergone three generations of development and was finally optimized for highly selective BH3 mimicking small oligopeptide ABT-199 (VEN). With its activity of specifically blocking BCL-2 protein, it can change the apoptosis threshold of bone marrow blast cells and cooperate with azacitidine (AZA) to treat MDS in vitro. This paper provides a brief review of the mechanisms of BCL-2 inhibitors, drug development processes, and key clinical trials in MDS.