Telomeres and Telomerase in Pediatric Acute Myeloid Leukemia
Delay in blood cell count recovery after chemotherapy is the most commonly observed toxicity in pediatric acute myeloid leukemia (AML), and 80% of patients develop severe toxicities during treatment. Delay in therapy due to a low white blood cell (WBC) count places individuals at risk for severe infections, and is associated with an increased mortality. We are investigating genetic markers for risk for AML treatment-related toxicities, such as unexpectedly prolonged periods of low WBC count after chemotherapy. The genetic marker we are studying is an enzyme called telomerase, which maintains telomere length. Genetic material, or DNA, is protected by a telomere cap at the end of each DNA strand. Telomeres that are markedly shortened due to a defect in telomerase result in a risk for developing AML as well as bone marrow failure. Individuals with these defects also have a heightened sensitivity to chemotherapy. We know that approximately 6% of adults with AML have telomerase defects, and though we do not yet know the rates of these defects in children with AML, we expect that they will be even more common than in the adult population. Shortened telomere length and telomerase mutations may explain why some children develop AML, as well as why some develop such severe treatment-related toxicities with AML therapy. The results of this research may lead to implementation of screening for these mutations in all children diagnosed with AML, and closer monitoring for toxicities, with potentially individualized treatment regimens, in those individuals where a mutation is found.