Study of the mechanism of cell death caused by peptides targeting CD47 in leukemia cell lines.

Gómez Morales, Luis (2017) Study of the mechanism of cell death caused by peptides targeting CD47 in leukemia cell lines. Maestría thesis, Universidad Autónoma de Nuevo León.

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CD47 activation through the C-terminus of thrombospondin-1 or its derived peptides (4N1K and PKHB1) induce regulated cell death (RCD) in several types of cancer. Recently, it was demonstrated that PKHB1, the first serum-stable CD47 agonist peptide, induce caspase-independent, calcium-dependent RCD in CLL cells, even in those resistant to conventional therapy. Therefore, the objective of the present work was to study the PKHB1-induced cell death mechanism in other types of leukemia. To that end, cell death induction was evaluated by flow cytometry, analyzing phosphatidilserine exposure (Ann-V) and plasma membrane permeability (PI), as well as caspase dependance (inhibitor Q-VD-OPH) or calcium dependance (BAPTA, calcium chelator). The results show that PKHB1 is a better inductor of cell death, compared to 4N1K, and it is selective to different types of leukemia (MEC-1, CEM, Junket, K562, HL-60, L5178Y-R), since it does not kill human peripheral mononuclear cells, nor cells derived from lymphoid organs of healthy mice. PKHB1-induced killing is caspase-independent in all cases. Additionally, in CEM (human T lymphoblasts of acute lymphocytic leukemia, the principal type of childhood cancer) and L5178Y-R (murine T lymphoblasts) cells, death is not modulated by co-culture with chemoprotective bone marrow stromal cells; calcium chelation, however, inhibits PKHB1-induced cell death. Together, the results indicate that PKHB1 is effective in different types of leukemia, and induce caspase-independent, microenvironment-independent calcium-dependent RCD, in leukemic T lymphocytes. These results suggest that PKHB1-induced RCD could be conserved in different types of leukemia, and set the basis for further studies on murine models.

Tipo de elemento: Tesis (Maestría)
Información adicional: Master of Science with orientation in Immunobiology
Divisiones: Ciencias Biológicas
Usuario depositante: Lic. Josimar Pulido
Fecha del depósito: 19 Jul 2018 19:37
Última modificación: 03 Dic 2019 17:14

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