Targeting of these key BCR-ABL downstream genes provides an opportunity to eradicate LSCs, as shown in our work that identifies the Alox5 gene as a key regulator of the function of CML LSCs.
We have shown that Alox5 is a critical regulator of leukemia stem cells (LSCs) in a BCR-ABL-induced chronic myeloid leukemia (CML) mouse model, and we hypothesize that the Alox5 pathway represents a major molecular network that regulates LSC function.
Based on these results, the 5-LO inhibitor zileuton has been introduced in clinical trials as a therapeutic option to target the LSC although its effect on primary human CML LSC has not been studied.