Evaluation of the primitive fraction by functional in vitro assays at the RNA and DNA level represents a novel tool for complementing molecular monitoring in chronic myeloid leukemia.

Autor:	Ruiz MS; Centro de Investigaciones Oncológicas-Fundación Cáncer (CIO-FUCA), Ciudad Autónoma de Buenos Aires, Argentina., Sanchez MB; Centro de Investigaciones Oncológicas-Fundación Cáncer (CIO-FUCA), Ciudad Autónoma de Buenos Aires, Argentina.; Argenomics, Ciudad Autónoma de Buenos Aires, Argentina., Gutiérrez L; Instituto de Medicina Experimental, CONICET/Academia Nacional de Medicina, Ciudad Autónoma de Buenos Aires, Argentina., Koile D; Instituto de Investigación en Biomedicina de Buenos Aires (IBioBA), CONICET, Partner Institute of the Max Planck Society, Ciudad Autónoma de Buenos Aires, Argentina., Yankilevich P; Instituto de Investigación en Biomedicina de Buenos Aires (IBioBA), CONICET, Partner Institute of the Max Planck Society, Ciudad Autónoma de Buenos Aires, Argentina., Mosqueira C; Argenomics, Ciudad Autónoma de Buenos Aires, Argentina., Cranco S; Instituto Alexander Fleming, Ciudad Autónoma de Buenos Aires, Argentina., Custidiano MDR; Instituto Alexander Fleming, Ciudad Autónoma de Buenos Aires, Argentina., Freitas J; Hospital Nacional Posadas, El Palomar, Buenos Aires, Argentina., Foncuberta C; Instituto Alexander Fleming, Ciudad Autónoma de Buenos Aires, Argentina., Moiraghi B; Hospital J. M. Ramos Mejía, Ciudad Autónoma de Buenos Aires, Argentina., Pavlovsky C; Fundaleu, Ciudad Autónoma de Buenos Aires, Argentina., Pérez MA; Hospital Interzonal General de Agudos, Prof. Dr. R. Rossi, La Plata, Buenos Aires, Argentina., Ventriglia V; Hospital Nacional Posadas, El Palomar, Buenos Aires, Argentina., Ávalos JS; Instituto Alexander Fleming, Ciudad Autónoma de Buenos Aires, Argentina., Mordoh J; Centro de Investigaciones Oncológicas-Fundación Cáncer (CIO-FUCA), Ciudad Autónoma de Buenos Aires, Argentina., Larripa I; Instituto de Medicina Experimental, CONICET/Academia Nacional de Medicina, Ciudad Autónoma de Buenos Aires, Argentina., Bianchini M; Centro de Investigaciones Oncológicas-Fundación Cáncer (CIO-FUCA), Ciudad Autónoma de Buenos Aires, Argentina.
Jazyk:	angličtina
Zdroj:	Oncotarget [Oncotarget] 2018 Apr 17; Vol. 9 (29), pp. 20255-20264. Date of Electronic Publication: 2018 Apr 17 (Print Publication: 2018).
DOI:	10.18632/oncotarget.24749
Abstrakt:	Quantification of BCR-ABL1 mRNA levels in peripheral blood of chronic myeloid leukemia patients is a strong indicator of response to tyrosine-kinase inhibitors (TKI) treatment. However, additional prognostic markers are needed in order to better classify patients. The hypothesis of leukemic stem cells (LSCs) heterogeneity and persistence, suggests that their functional evaluation could be of clinical interest. In this work, we assessed the primitive and progenitor fractions in patients at diagnosis and during TKI treatment using functional in vitro assays, defining a "functional leukemic burden" (FLB). We observed that the FLB was reduced in vivo in both fractions upon treatment. However, different FLB levels were observed among patients according to their response to treatment, suggesting that quantification of the FLB could complement early molecular monitoring. Given that FLB assessment is limited by BCR-ABL1 mRNA expression levels, we developed a novel detection method of primitive cells at the DNA level, using patient-specific primers and direct nested PCR in colonies obtained from functional in vitro assays. We believe that this method could be useful in the context of discontinuation trials, given that it is unknown whether the persistent leukemic clone represents LSCs, able to resume the leukemia upon TKI removal. Competing Interests: CONFLICTS OF INTEREST We state that this study was supported financially by a Novartis grant; Dr. Michele Bianchini has received speaker fees from Novartis; all other authors declare no competing financial interests.
Databáze:	MEDLINE
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