SF3B1 gene mutations are the most common spliceosome mutations seen in myelodysplastic syndrome (MDS) patients. Though it is well known SF3B1 mutations cause downstream changes in erythroid differentiation and the cell cycle, which leads to malignancy, metabolic changes arising from this mutation are unknown. We conducted RNA sequencing from SF3B1-mutant MDS patient samples and found several genes related to metabolism were alternatively spliced. Of these, LUC7L2 was selected as our target as previous studies show its involvement in promoting oxidative phosphorylation (OXPHOS) via various downstream mechanisms when knocked down.We show that OXPHOS is increased in MOLM-13 myeloid malignant cells when LUC7L2 is inhibited. The results suggested that this gene, which is alternatively spliced and shows lower expression in SF3B1-mutant MDS, increases myeloid malignant dependence on OXPHOS.
Cisneros, Carlos H. Jr; Inguva, Anagha; Tolison, Hunter; Amaya, Maria; and Jordan, Craig, "OXPHOS Inhibition via LUC7L2 as a Target for SF3B1-Mutant Myelodysplastic Syndrome" (2022). MEDI 8127 Scholarly Activities Pre-Clerkship. 30.