New gene target found for acute myeloid leukemiaFebruary 5, 2019
Konstantinos Tzelepis et al demonstrated a plausible therapeutic potential of splicing kinase gene (SRPK1) in treating acute myeloid leukemia (AML). Scientists found that inhibition of the SRPK1 altered various gene isoforms, including BRD4 specific to mixed lineage leukemia (MLL), rearranged AML. BRD4, which is thought to be involved in anti-leukemogenesis, is already a validated drug target for leukemia. The study found the effect of a specific agent SPHINX31 to have a remarkable effect in the inhibition of SRPK1. The effect on BRD4 isoform suggests that it acts as a key mediator of the anti-leukemic effects brought about by SPHINX31. This was demonstrated in immunocompromised mice by transplanting the patient-derived
human MLL rearranged AML cells. Treatment with SPHINX31 was shown to prolong the survival of mice, which was brought about by cell cycle arrest of the leukemic cells without any noticeable toxicity to healthy cells. The scientists propose that inhibition of SRPK1 should be investigated in the treatment of other malignancies where BRD4 isoform balance plays a role as in metastatic breast cancer.
Source: Nature Communications volume 9, Article number: 5378 (2018) https://www.nature.com/articles/s41467-018-07620-0