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

This study examined mechanisms for this resistance, including protective effects conferred by bone marrow stromal components. T cell acute leukemia cells co-cultured with mesenchymal stem cells demonstrated significantly enhanced survival against parthenolide (73+/-11%) compared to cells treated without mesenchymal stem cell support (11+/-9%). Direct cell contact between mesenchymal cells and leukemia cells was not required to afford protection from parthenolide. Mesenchymal stem cells released thiols and protected leukemia cells from reactive oxygen species stress, which is associated with parthenolide cytotoxicity. Blocking cystine uptake by mesenchymal stem cells, using a small molecule inhibitor, prevented thiol release and significantly reduced leukemia cell resistance to parthenolide. These data indicate it may be possible to achieve greater toxicity to childhood T cell acute lymphoblastic leukemia by combining parthenolide with inhibitors of cystine uptake. PMID: 29773592 [PubMed - as supplied by publisher]
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research