PARP-1 improves leukemia outcomes by inducing parthanatos during chemotherapy.

Previous chemotherapy research has focused almost exclusively on apoptosis. Here, a standard frontline drug combination of cytarabine and idarubicin induces distinct features of caspase-independent, poly(ADP-ribose) polymerase 1 (PARP-1)-mediated programmed cell death "parthanatos" in acute myeloid leukemia (AML) cell lines (n = 3/10 tested), peripheral blood mononuclear cells from healthy human donors (n = 10/10 tested), and primary cell samples from patients with AML (n = 18/39 tested, French-American-British subtypes M4 and M5). A 3-fold improvement in survival rates is observed in the parthanatos-positive versus -negative patient groups (hazard ratio [HR] = 0.

Enhancing CAR-T Cell Therapy with Functional Nucleic Acids.

Chimeric antigen receptor (CAR) T cell therapy is a relatively new form of immunotherapy that has had success in treating patients with hematologic malignancies, leading to three recent United States Food and Drug Administration approvals. However, several challenges hinder the widespread use of CAR-T therapy. Here, we review the application of functional nucleic acids such as aptamers and ribozymes as novel tools to improve a variety of steps in CAR-T cell therapy development.