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تسجيل

Leukemia Stem Cells

المؤلف:  Hoffman, R., Benz, E. J., Silberstein, L. E., Heslop, H., Weitz, J., & Salama, M. E.

المصدر:  Hematology : Basic Principles and Practice

الجزء والصفحة:  8th E , P947

2026-10-11

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Normal human HSCs are characterized by their capacity for self renewal and multilineage differentiation, properties that can only be assessed in vivo using functional assays such as xenotransplantation into immune-deficient mouse models. The pioneering studies of John Dick and colleagues demonstrated that a similar cellular hierarchy exists in AML, in which rare cells with an immunophenotype similar to normal stem/progenitor cells are enriched for the capacity to initiate leukemia in xenotransplantation models. The stem cell model of AML and other hematologic malignancies is discussed in detail elsewhere.

Work from many laboratories has led to the identification of several cell surface antigens that are preferentially expressed on leukemia stem cells (LSCs) compared with normal HSCs, including CD123, CD99, TIM3, and others. No single marker identified to date is sufficient to perfectly discriminate HSCs from LSCs. Combinatorial approaches may improve the ability to identify and selectively target LSCs. LSCs have several biological properties that cause them to resist chemotherapy and create an important reservoir for disease relapse, including expression of drug efflux pumps, resistance to apoptosis, and cell cycle quiescence.

More recently, a “pre-LSC” population has been described. These are cells with an HSC immunophenotype that can be recovered from the bone marrow of patients with AML and are capable of engraftment and multilineage differentiation in vivo in immunodeficient mice. Single cell genotyping has revealed that pre-LSCs often harbor the same class of mutations detected in individuals with CH (e.g., DNMT3A, TET2) but lack the full complement of mutations found in the bulk AML sample, suggesting that they are ancestral. The contribution of these preleukemic stem cells to chemotherapy resistance and relapse remains to be determined.