Concise Review: Exploiting Unique Biological Features of Leukemia Stem Cells for Therapeutic Benefit. (23rd April 2019)

• Record Type: Journal Article
• Authors: Zhang, Haojian; Li, Shaoguang
• Is Part Of: Stem cells translational medicine. Volume 8:Number 8(2019)
• Page Start: 768
• Page End: 774
• Publication Date: 2019-04-23
• Subjects: Cancer stem cells -- BCR-ABL -- Chronic myeloid leukemia -- Bone marrow -- Leukemia; Stem cells -- Periodicals; Regenerative medicine -- Periodicals; Periodicals; 616.0277405
• DOI: 10.1002/sctm.18-0247
• Languages: English
• ISSNs: 2157-6564

Abstract

Abstract: Cancer stem cells play a critical role in disease initiation and insensitivity to chemotherapy in numerous hematologic malignancies and some solid tumors, and these stem cells need to be eradicated to achieve a cure. Key to successful targeting of cancer stem cells is to identify and functionally test critical target genes and to fully understand their associated molecular network in these stem cells. Human chronic myeloid leukemia (CML) is well accepted as one of the typical types of hematopoietic malignancies that are derived from leukemia stem cells (LSCs), serving as an excellent model disease for understanding the biology of LSCs and developing effective, selective, and curative strategies through targeting LSCs. Here, we discuss LSCs in CML with a focus on identification of unique biological features of these stem cells to emphasize the feasibility and significance of specific targeting of LSCs while sparing normal stem cell counterparts in leukemia therapy. Stem Cells Translational Medicine 2019;8:768–774 : Abstract : BCR-ABL changes activities of some signaling pathways independently of its kinase activity. Inhibition of BCR-ABL kinase activity by tyrosine kinase inhibitors (TKIs) alters numerous signaling pathways in a leukemia stem cell (LSC) of chronic myeloid leukemia (CML), including JAK/STAT and PI3K/AKT. However, some signaling pathways activated by BCR-ABL are not changed, including Alox5, Alox15, stearoyl-CoA desaturase 1, and B lymphocyte kinase, providing an explanation for TKI resistance of LSCs in CML.