Pyruvate kinase liver and red blood cell (PKLR) (PKLR)

The PKLR gene encodes the L and R isoforms of pyruvate kinase, which are essential enzymes in the glycolytic pathway (UniProt P30613). These enzymes catalyze the final step of glycolysis, converting phosphoenolpyruvate to pyruvate and generating ATP. In red blood cells, the R-type isoform is the primary source of energy; consequently, mutations in the PKLR gene lead to pyruvate kinase deficiency (PKD). PKD is a rare genetic disorder characterized by chronic non-spherocytic hemolytic anemia due to the premature destruction of ATP-depleted erythrocytes (NCBI Gene: 5313). Therapeutic strategies targeting the PKLR gene in autologous CD34+ hematopoietic stem cells utilize ex vivo gene therapy to restore enzymatic function. For instance, the investigational therapy RP-L301 uses a lentiviral vector to deliver a functional PKLR gene into a patient's own stem cells (Rocket Pharmaceuticals). Following a conditioning regimen, these modified cells are re-infused into the patient to engraft and produce functional red blood cells. This approach aims to provide a durable, potentially curative solution for patients with severe PKD by correcting the underlying metabolic defect (ClinicalTrials.gov NCT03686150). Monitoring efficacy involves measuring improvements in hemoglobin levels and reductions in markers of hemolysis like bilirubin and lactate dehydrogenase.

Other names

Pyruvate kinase liver and red blood cellPKLPKRLRPKPK1R-type pyruvate kinaseL-type pyruvate kinase

Ex vivo lentiviral-mediated gene addition to autologous CD34+ hematopoietic stem cells to restore pyruvate kinase activity in the erythroid lineage.