IDENTIFICATION OF LEUKEMIC STEM CELLS FOR TARGETED THERAPY OF PATIENTS WITH ACUTE MYELOID LEUKEMIA
Gluzman D.F., Sklyarenko L.М., Ivanovskaya T.S., Philchenkov A.A., Zavelevich M.P., Koval S.V., Polishchuk A.S.
- R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv, Ukraine
The review summarizes briefly the data on the history of the discovery of the pluripotent stem hematopoietic cells (PSHC), the role of the foreign and national scientists in the development of the unipotent scheme of the normal hematopoiesis. The issues related to the identification of the human leukemic stem cells (LSC) are spotlighted with the emphasis on the comparison of the immunophenotypes of LSC and leukemic blasts in different types of the acute myeloid leukemia delineated according to FAB classification and the modernized WHO classification (2016). The use of flow cytometry and panels of monoclonal antibodies against new differentiation antigens allowed elucidating the distinct immunophenotypic features of LSC, PSHC and early hematopoietic progenitor cells having been at the origin of different forms of acute myeloid leukemias (AML). According to modern concepts, the bulk of leukemic cells in AML patients are no capable of self-renewal and active proliferation. Only LSC representing mostly CD34+CD38– cell fraction and accounting for less than 1% of total leukemic cells possess the clonal properties. The novel concept of targeted therapy provides for designing the agents affecting selectively LSC and not PSHC participating in the recovery of normal hematopoiesis. The possible developments leading to the elaboration of novel selective medicinal products directed against specific markers of the surface membrane of LSC, intracellular signaling pathways and microenvironment of LSC are also reviewed.
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