In Vitro Purging of Acute Lymphoblastic Leukemia (B-ALL) Cells with the Use of PTL, DMAPT, or PU-H71

利用 PTL、DMAPT 或 PU-H71 体外清除急性淋巴细胞白血病 (B-ALL) 细胞

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作者:Ana Elenka Ortiz-Reyes,Sergio García-Sánchez,Montserrat Serrano,Juan Carlos Núñez-Enriquez,José Antonio Alvarado-Moreno,Juan José Montesinos,Guadalupe Fajardo-Orduña,Monica L Guzman,Miguel Angel Villasis-Keever,Ismael Mancilla-Herrera,Hector Mayani,Antonieta Chavez-Gonzalez

Abstract

Acute lymphoblastic leukemia (ALL) is a hematopoietic disorder that mainly affects the child population, and it is characterized by the presence of lymphoid progenitor or precursor cells with different genetic alterations. The origin of this disease is controversial, since some authors assumed that leukemic transformation occurs in a lymphoid progenitor, and there is also evidence that suggests the existence of leukemic initiating cells (LIC). PTL, DMAPT, and PU-H71 are agents that have been shown to eliminate bulk and stem cells from myeloid leukemias, but this effect has not been analyzed in lymphoblastic leukemias. In this study, we evaluated the effect of these compounds in different populations from pediatric B-ALL. For this, bone marrow samples from pediatric patients without treatment were obtained and cultured in the presence or absence of PTL, DMAPT, and PU-H71. The viability and apoptosis index were analyzed by flow cytometry in different hematopoietic subpopulations. These observations indicate that PTL and DMAPT are able to reduce B-ALL cells with a minimum effect in normal hematopoietic and non-hematopoietic cells. In contrast, PU-H71 was able to reduce the leukemic population and had a minimal effect in normal cells. These results present evidence that PTL and DMAPT are able to abrogate in vitro different populations of B-ALL and could represent a possibility of treatment, as well as prevent disease progression or relapse.

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