Investigating chemoresistance to improve sensitivity of childhood T-cell acute lymphoblastic leukemia to parthenolide.

摘要: Current therapies for childhood T-cell acute lymphoblastic leukemia have increased survival rates to above 85% in developed countries. Unfortunately, some patients fail respond therapy and many suffer from serious side effects, highlighting the need investigate other agents treat this disease. Parthenolide, a nuclear factor kappa (κ)B inhibitor reactive oxygen species inducer, has been shown excellent anti-cancer activity pediatric xenografts, with minimal effects on normal hemopoietic cells. However, initiating cell populations remain resistant parthenolide. This study examined mechanisms resistance, including protective conferred by bone marrow stromal components. cells co-cultured mesenchymal stem demonstrated significantly enhanced against parthenolide (73±11%) compared treated without support (11±9%). Direct contact between was not required afford protection Mesenchymal released thiols protected stress, which is associated cytotoxicity. Blocking cystine uptake cells, using small molecule inhibitor, prevented thiol release reduced resistance These data indicate it may be possible achieve greater toxicity combining inhibitors of uptake.