Theragnostic strategies harnessing the self-renewal pathways of stem-like cells in the acute myeloid leukemia. (September 2022)

• Record Type: Journal Article
• Authors: Bhattacharjee, Rahul; Ghosh, Sharad; Nath, Arijit; Basu, Asmita; Biswas, Ojaswi; Patil, Chandragauda R.; Kundu, Chanakya Nath
• Is Part Of: Critical reviews in oncology/hematology. Volume 177(2022)
• Publication Date: 2022-09
• Subjects: OS Overall survival -- EFS Event-free survival -- AML Acute myeloid Leukemia -- LSC Leukemic Stem Cells -- MDR Minimal Residual Disease -- HSCs Hematopoietic stem -- CD Cluster of Differentiation -- GPCR G protein-coupled receptors -- PIP3 phosphatidylinositol (3, 4, 5)-trisphosphate -- PIP2 Phosphatidylinositol (4, 5)-bisphosphate -- PTEN Phosphatase and -- BAD BCL2 associated agonist of cell death -- DNA-PK DNA-dependent protein kinase -- MRP1 Multidrug Resistance-associated Protein1 -- TSC1 Tuberous sclerosis 1 -- S6K1 S6 kinase -- MLL Mixed Lineage Leukemia -- FOXO Fork head box O -- PKBs protein kinase B -- FUT4 Fucosyltransferase 4 -- EGFL7 Epidermal Growth factor-like Domain 7 -- Hh Hedgehog -- DUBs Deubiquitylase -- UCHL5 Ubiquitin carboxyl-terminal hydrolase isoenzyme L5 -- GLI3R GLI3 transcriptional repressor -- HIF-1 Hypoxia-inducible factor-1a -- PcG Polycomb -- LPHN1 Latrophilin-1 -- CK2 Casein Kinase2 -- ATM Ataxia Telangiectasia Mutated kinase -- NICD Notch Intracellular domain -- AFC Applicable for other cancer in trial and preclinical in AML-LSC; Acute myeloid leukemia -- Leukemia stem cells-like cells -- Signaling pathways -- Self-renewal pathways -- Chemoresistance; Oncology -- Periodicals; Hematology -- Periodicals; 616.994
• DOI: 10.1016/j.critrevonc.2022.103753
• Languages: English
• ISSNs: 1040-8428

Abstract

Abstract: Acute myelogenous leukemia (AML) is a genetically heterogeneous and aggressive cancer of the Hematopoietic Stem/progenitor cells. It is distinguished by the uncontrollable clonal growth of malignant myeloid stem cells in the bone marrow, venous blood, and other body tissues. AML is the most predominant of leukemias occurring in adults (25%) and children (15–20%). The relapse after chemotherapy is a major concern in the treatment of AML. The overall 5-year survival rate in young AML patients is about 40–45% whereas in the elderly patients it is less than 10%. Leukemia stem-like cells (LSCs) having the ability to self-renew indefinitely, repopulate and persist longer in the G0/G1 phase play a crucial role in the AML relapse and refractoriness to chemotherapy. Hence, novel treatment strategies and diagnostic biomarkers targeting LSCs are being increasingly investigated. Through this review, we have explored the signaling modulations in the LSCs as the theragnostic targets. The significance of the self-renewal pathways in overcoming the treatment challenges in AML has been highlighted. Highlights: AML is a lethal hematologic malignancy develops from stem cells or progenitor cells. This review discusses AML-LSC pathways, both classical and non-classical, for proliferative advancement and chemoresistance. Elucidates theragnostic targeting of the self-harnessing pathway to cause AML-LSC regression. Discusses novel target sites in impeding AML-LSCs.