title: Targeting acute myeloid leukemia stem cell signaling by natural products.
abstract: Acute myeloid leukemia (AML) is the most commonly diagnosed leukemia in adults (25%) and comprises 15-20% in children. It is a genetically heterogeneous aggressive disease characterized by the accumulation of somatically acquired genetic changes, altering self-renewal, proliferation, and differentiation of hematopoietic progenitor cells, resulting in uncontrolled clonal proliferation of malignant progenitor myeloid cells in the bone marrow, peripheral blood, and occasionally in other body tissues. Treatment with modern chemotherapy regimen (cytarabine and daunorubicin) usually achieves high remission rates, still majority of patients are found to relapse, resulting in only 40-45% overall 5 year survival in young patients and less than 10% in the elderly AML patients. The leukemia stem cells (LSCs) are characterized by their unlimited self-renewal, repopulating potential and long residence in a quiescent state of G0/G1phase. LSCs are considered to have a pivotal role in the relapse and refractory of AML. Therefore, new therapeutic strategies to target LSCs with limited toxicity towards the normal hematopoietic population is critical for the ultimate curing of AML. Ongoing research works with natural products like parthenolide (a natural plant extract derived compound) and its derivatives, that have the ability to target multiple pathways that regulate the self-renewal, growth and survival of LSCs point to ways for a possible complete remission in AML. In this review article, we will update and discuss various natural products that can target LSCs in AML.
authors.affiliation: Translational Research Institute, Academic Health System, Hamad Medical Corporation, PO Box 3050, Doha, Qatar. SSivaraman@hamad.qa.
authors.forename: Kodappully Sivaraman
authors.identifier: 0000-0003-4669-1890
authors.initials: KS
authors.lastname: Siveen
authors.affiliation: Translational Research Institute, Academic Health System, Hamad Medical Corporation, PO Box 3050, Doha, Qatar.
authors.forename: Shahab
authors.initials: S
authors.lastname: Uddin
authors.affiliation: Translational Research Institute, Academic Health System, Hamad Medical Corporation, PO Box 3050, Doha, Qatar.
authors.forename: Ramzi M
authors.initials: RM
authors.lastname: Mohammad
mesh_terms: D000328:Adult; D001688:Biological Products / Q000494:pharmacology* / Q000627:therapeutic use; D002648:Child; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000378:metabolism; D058990:Molecular Targeted Therapy; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D001688:Biological Products
keywords: Acute myeloid leukemia; Leukemia stem cells; Natural products; Self-renewal