Chronic Myeloid Leukemia Stem Cell Biology
نویسندگان
چکیده
Leukemia progression and relapse is fueled by leukemia stem cells (LSC) that are resistant to current treatments. In the progression of chronic myeloid leukemia (CML), blast crisis progenitors are capable of adopting more primitive but deregulated stem cell features with acquired resistance to targeted therapies. This in turn promotes LSC behavior characterized by aberrant self-renewal, differentiation, and survival capacity. Multiple reports suggest that cell cycle alterations, activation of critical signaling pathways, aberrant microenvironmental cues from the hematopoietic niche, and aberrant epigenetic events and deregulation of RNA processing may facilitate the enhanced survival and malignant transformation of CML progenitors. Here we review the molecular evolution of CML LSC that promotes CML progression and relapse. Recent advances in these areas have identified novel targets that represent important avenues for future therapeutic approaches aimed at selectively eradicating the LSC population while sparing normal hematopoietic progenitors in patients suffering from chronic myeloid malignancies.
منابع مشابه
Signaling pathways involved in chronic myeloid leukemia pathogenesis: the importance of targeting Musashi2-Numb signaling to eradicate leukemia stem cells
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 ...
متن کاملAdvances in Hematopoietic Stem Cell Mobilization and Peripheral Blood Stem Cell Transplantation
Hematopoietic stem/progenitor cells (HSPCs) which give rise to different blood cell types are present within the bone marrow microenvironment, especially in flat bones such as skull, vertebrae, pelvis and chest. Interacting factors such as stromal derived factor-1/CXCR4, very late antigen-4/vascular cell adhesion molecule-1, Lymphocyte function-associated antigen-1/ intercellular adhesion molec...
متن کاملThe long-term outcome and efficacy of PR1/BCR-ABL multipeptides vaccination in chronic myeloid leukemia: results of a 7-year longitudinal investigation
Background: Although Imatinib has revolutionized the treatment of chronic myeloid leukemia (CML), not all patients reach complete remission and a considerable proportion of the patients develop resistance to Imatinib. Material and Methods: In an attempt to increase the tail on the survival curve, we conducted a Phase I/II study of PR1/BCR-ABL multipeptides vaccination trial in CML patients wit...
متن کاملStudy of STAT3 Expression in Different Phases of Patients with Chronic Myeloid Leukemia
Background and Aim: Chronic myeloid leukemia(CML) is a clonal myeloproliferative disease, characterized by BCR/ABL translocation. Using tyrosine kinase inhibitors such as Imatinib, treatment for this disease has progressed remarkably. However, resistance to tyrosine kinase inhibitor is a major obstacle. Signal transducer and activator of transcription 3(STAT3) is an important transcription fact...
متن کاملPreliminary Results of Allogenic Hematopoietic Stem Cell Transplantation of non-M3 Acute Myeloid Leukemia
Background: Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) is used as treatment of choice for patients with acute myeloid leukemia (AML). We aimed to evaluate the prognostic factors in 2-year overall survival of patients with non-M3 AML who underwent allogenic HSCT. Methods: This is a Cross sectional retrospective study. Demographic data and study of variables such as age...
متن کاملRole of Oxidative Stress in Modulating Unfolded Protein Response Activity in Chronic Myeloid Leukemia Cell Line
Background: Recently, it has been revealed that tyrosine kinase inhibitors (TKIs) act through inducing both oxidative and endoplasmic reticulum (ER) stress in chronic myeloid leukemia cells. However, ER stress signaling triggers both apoptotic and survival processes within cells. Nevertheless, mechanisms by which TKIs avoid the pro-survival effects are not clear. The aim of this study was to ev...
متن کامل