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Plasma Hsp90 Level as a Marker of Early Acute Lymphoblastic Leukemia Engraftment and Progression in Mice

Current monitoring of acute lymphoblastic leukemia (ALL) in living mice is based on FACS analysis of blood hCD45+ cells. In this work, we evaluated the use of human IGFBP2, B2M or Hsp90 as soluble markers of leukemia. ELISA for B2M and IGFBP2 resulted in high background levels in healthy animals, pr...

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Autores principales: Milani, Mateus, Laranjeira, Angelo Brunelli Albertoni, de Vasconcellos, Jaíra Ferreira, Brandalise, Silvia Regina, Nowill, Alexandre Eduardo, Yunes, José Andrés
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4466233/
https://www.ncbi.nlm.nih.gov/pubmed/26068922
http://dx.doi.org/10.1371/journal.pone.0129298
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author Milani, Mateus
Laranjeira, Angelo Brunelli Albertoni
de Vasconcellos, Jaíra Ferreira
Brandalise, Silvia Regina
Nowill, Alexandre Eduardo
Yunes, José Andrés
author_facet Milani, Mateus
Laranjeira, Angelo Brunelli Albertoni
de Vasconcellos, Jaíra Ferreira
Brandalise, Silvia Regina
Nowill, Alexandre Eduardo
Yunes, José Andrés
author_sort Milani, Mateus
collection PubMed
description Current monitoring of acute lymphoblastic leukemia (ALL) in living mice is based on FACS analysis of blood hCD45+ cells. In this work, we evaluated the use of human IGFBP2, B2M or Hsp90 as soluble markers of leukemia. ELISA for B2M and IGFBP2 resulted in high background levels in healthy animals, precluding its use. Conversely, plasma levels of Hsp90 showed low background and linear correlation to FACS results. In another experiment, we compared Hsp90 levels with percentage of hCD45+ cells in blood, bone marrow, liver and spleen of animals weekly sacrificed. Hsp90 levels proved to be a superior method for the earlier detection of ALL engraftment and correlated linearly to ALL burden and progression in all compartments, even at minimal residual disease levels. Importantly, the Hsp90/hCD45+ ratio was not altered when animals were treated with dexamethasone or a PI3K inhibitor, indicating that chemotherapy does not directly interfere with leukemia production of Hsp90. In conclusion, plasma Hsp90 was validated as a soluble biomarker of ALL, useful for earlier detection of leukemia engraftment, monitoring leukemia kinetics at residual disease levels, and pre-clinical or mouse avatar evaluations of anti-leukemic drugs.
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spelling pubmed-44662332015-06-25 Plasma Hsp90 Level as a Marker of Early Acute Lymphoblastic Leukemia Engraftment and Progression in Mice Milani, Mateus Laranjeira, Angelo Brunelli Albertoni de Vasconcellos, Jaíra Ferreira Brandalise, Silvia Regina Nowill, Alexandre Eduardo Yunes, José Andrés PLoS One Research Article Current monitoring of acute lymphoblastic leukemia (ALL) in living mice is based on FACS analysis of blood hCD45+ cells. In this work, we evaluated the use of human IGFBP2, B2M or Hsp90 as soluble markers of leukemia. ELISA for B2M and IGFBP2 resulted in high background levels in healthy animals, precluding its use. Conversely, plasma levels of Hsp90 showed low background and linear correlation to FACS results. In another experiment, we compared Hsp90 levels with percentage of hCD45+ cells in blood, bone marrow, liver and spleen of animals weekly sacrificed. Hsp90 levels proved to be a superior method for the earlier detection of ALL engraftment and correlated linearly to ALL burden and progression in all compartments, even at minimal residual disease levels. Importantly, the Hsp90/hCD45+ ratio was not altered when animals were treated with dexamethasone or a PI3K inhibitor, indicating that chemotherapy does not directly interfere with leukemia production of Hsp90. In conclusion, plasma Hsp90 was validated as a soluble biomarker of ALL, useful for earlier detection of leukemia engraftment, monitoring leukemia kinetics at residual disease levels, and pre-clinical or mouse avatar evaluations of anti-leukemic drugs. Public Library of Science 2015-06-11 /pmc/articles/PMC4466233/ /pubmed/26068922 http://dx.doi.org/10.1371/journal.pone.0129298 Text en © 2015 Milani et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Milani, Mateus
Laranjeira, Angelo Brunelli Albertoni
de Vasconcellos, Jaíra Ferreira
Brandalise, Silvia Regina
Nowill, Alexandre Eduardo
Yunes, José Andrés
Plasma Hsp90 Level as a Marker of Early Acute Lymphoblastic Leukemia Engraftment and Progression in Mice
title Plasma Hsp90 Level as a Marker of Early Acute Lymphoblastic Leukemia Engraftment and Progression in Mice
title_full Plasma Hsp90 Level as a Marker of Early Acute Lymphoblastic Leukemia Engraftment and Progression in Mice
title_fullStr Plasma Hsp90 Level as a Marker of Early Acute Lymphoblastic Leukemia Engraftment and Progression in Mice
title_full_unstemmed Plasma Hsp90 Level as a Marker of Early Acute Lymphoblastic Leukemia Engraftment and Progression in Mice
title_short Plasma Hsp90 Level as a Marker of Early Acute Lymphoblastic Leukemia Engraftment and Progression in Mice
title_sort plasma hsp90 level as a marker of early acute lymphoblastic leukemia engraftment and progression in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4466233/
https://www.ncbi.nlm.nih.gov/pubmed/26068922
http://dx.doi.org/10.1371/journal.pone.0129298
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