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.
Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraydah, 51452 Al-Qaseem, Saudi Arabia.
P F
PF
Seke Etet
L
L
Vecchio
A H
AH
Nwabo Kamdje
D000818:Animals; D060833:Cellular Microenvironment; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism* / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism*