Signaling pathways involved in chronic myeloid leukemia pathogenesis: the importance of targeting Musashi2-Numb signaling to eradicate leukemia stem cells

• Main Authors: Foruzan Moradi, Sadegh Babashah, Majid Sadeghizadeh, Arsalan Jalili, Abbas Hajifathali, Elham Roshandel
• Format: Article
• Language: English
• Published: Mashhad University of Medical Sciences 2019-06-01
• Series: Iranian Journal of Basic Medical Sciences
• Subjects: BCR-ABL1; Chronic myeloid leukemia; Cancer stem cells; Signaling pathways; Self-renewal; Targeted therapy
• Online Access: http://ijbms.mums.ac.ir/article_12723_d9b444b5e7550b9883ddcd7802ad293e.pdf

Objective(s): Chronic myeloid leukemia (CML) is a myeloid clonal proliferation disease defining by the presence of the Philadelphia chromosome that shows the movement of BCR-ABL1. In this study, the critical role of the Musashi2-Numb axis in determining cell fate and relationship of the axis to important signaling pathways such as Hedgehog and Notch that are essential for self-renewal pathways in CML stem cells will be reviewed meticulously.Materials and Methods: In this review, a PubMed search using the keywords of Leukemia, signaling pathways, Musashi2-Numb was performed, and then we summarized different research works.Results: Although tyrosine kinase inhibitors such as Imatinib significantly kill and remove the cell with BCR-ABL1 translocation, they are unable to target BCR-ABL1 leukemia stem cells. The main problem is stem cells resistance to Imatinib therapy. Therefore, the identification and control of downstream molecules/ signaling route of the BCR-ABL1 that are involved in the survival and self-renewal of leukemia stem cells can be an effective treatment strategy to eliminate leukemia stem cells, which supposed to be cured by Musashi2-Numb signaling pathway.Conclusion: The control of molecules /pathways downstream of the BCR-ABL1 and targeting Musashi2-Numb can be an effective therapeutic strategy for treatment of chronic leukemia stem cells. While Musashi2 is a poor prognostic marker in leukemia, in treatment and strategy, it has significant diagnostic value.