Signaling pathways in chronic myeloid leukemia and leukemic stem cell maintenance: Key role of stromal microenvironment

Chronic myeloid leukemia (CML) is caused by the malignant transformation of hematopoietic stem cells in leukemic stem cells. From the introduction of the anti-cancer drug imatinib, the therapy of CML has been positively transformed. However, following treatment most patients display a residual CML disease attributed to the presence of quiescent leukemic stem cells intrinsically resistant to imatinib. Considering that the later cancer cells lose their chemoresistance in vitro, it appears that the stromal microenvironment plays a crucial role in CML-affected cell chemoresistance. In the present review, we summarize and discuss the recent findings on signaling pathways through which stromal cells sustain CML leukemogenesis, as well as leukemic stem cell maintenance and chemoresistance.

► We review the recent findings on chronic myeloid leukemia pathogenesis.
► Stromal microenvironment anti-apoptotic molecules play a crucial role in CML.
► Chemoresistance to tyrosine kinase inhibitors mechanisms is discussed.
► New therapeutic approaches are summarized and discussed.