ONC213: a novel strategy to resensitize resistant AML cells to venetoclax through induction of mitochondrial stress.

Background: Venetoclax + azacitidine is a frontline treatment for older adult acute myeloid leukemia (AML) patients and a salvage therapy for relapsed/refractory patients who have been treated with intensive chemotherapy. While this is an important treatment option, many patients fail to achieve complete remission and of those that do, majority relapse. Leukemia stem cells (LSCs) are believed to be responsible for AML relapse and can be targeted through oxidative phosphorylation reduction.

The evolution and history of Vinca alkaloids: From the Big Bang to the treatment of pediatric acute leukemia.

An attractive flower from the island of Madagascar has in part saved the lives of thousands of children with acute lymphoblastic leukemia (ALL). Random mutations and alterations to the genome led to the evolution of genes encoding enzymes, which would provide the periwinkle flower an arsenal of secondary metabolites to survive within the Madagascar ecosystem. Of the over 200 alkaloid compounds synthesized by the periwinkle, vincristine and vinblastine are the two most well-known being used for chemotherapy treatments, including for children with ALL.

Pharmacogenomic Score Effectively Personalizes Treatment of Acute Myeloid Leukemia.

Purpose: Cytarabine (also known as ara-C) has been the backbone of acute myeloid leukemia (AML) chemotherapy for more than five decades. Recent pharmacogenomics-based 10-SNP ara-C (ACS10) scores showed low ACS10 (≤0) to be associated with poor outcomes in patients with AML treated with standard chemotherapy. Here, we evaluated the ACS10 score in the context of three different induction I regimens in patients with pediatric AML.

Combining the novel FLT3 and MERTK dual inhibitor MRX-2843 with venetoclax results in promising antileukemic activity against FLT3-ITD AML.

FMS-like tyrosine kinase 3 (FLT3) mutations occur in approximately one third of acute myeloid leukemia (AML) patients. FLT3-Internal tandem duplication (FLT3-ITD) mutations are the most common FLT3 mutations and are associated with a poor prognosis. Gilteritinib is a FLT3 inhibitor that is US FDA approved for treating adult patients with relapsed/refractory AML and a FLT3 mutation.