Cancer Stem Cells in the Development of Novel Therapeutics for Refractory Pediatric Leukemia
Abstract
Although treatment strategies for pediatric leukemia have improved overall survival rates in the recent past, relapse rates in certain subgroups such as infant leukemia remain unacceptably high. Despite undergoing extensive chemotherapy designed to target the rapidly proliferating leukemia cells, many of these children experience relapse. In refractory leukemia, the existence of cell populations with stemness characteristics, termed leukemia stem cells (LSCs), which remain quiescent and subsequently replenish the blast population, has been described. A significant body of evidence exists, derived largely from xenograft models of adult acute myeloid leukemia, to support the idea that LSCs may play a fundamental role in refractory disease. In addition, clinical studies have also linked LSCs with increased minimal residual disease, higher relapse rate, and decreased survival rates in these patients. Recently, a number of reports have addressed effective ways to utilize new-generation genomic sequencing and transcriptomic analyses to identify targeted therapeutic agents aimed at LSCs, while sparing normal hematopoietic stem cells. These data underscore the value of timely translation of knowledge from adult studies to the unique mo...Continue Reading
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