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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Milani, Mateus [1] ; Albertoni Laranjeira, Angelo Brunelli [1] ; de Vasconcellos, Jaira Ferreira [1] ; Brandalise, Silvia Regina [1] ; Nowill, Alexandre Eduardo [2] ; Yunes, Jose Andres [3, 1]
Total Authors: 6
Affiliation:
[1] Ctr Infantil Boldrini, Mol Biol Lab, Campinas, SP - Brazil
[2] Univ Estadual Campinas, FCM, CIPOI, Campinas, SP - Brazil
[3] Univ Estadual Campinas, FCM, Dept Med Genet, Campinas, SP - Brazil
Total Affiliations: 3
Document type: Journal article
Source: PLoS One; v. 10, n. 6 JUN 11 2015.
Web of Science Citations: 3
Abstract

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. (AU)

FAPESP's process: 12/12802-1 - Cooperating mutations, functional studies and antibodies against the mutant IL7R in acute lymphoblastic leukemia
Grantee:José Andrés Yunes
Support Opportunities: Regular Research Grants
FAPESP's process: 08/10034-1 - Bone marrow microenvironment and PI3K pathway in resistance to chemotherapy of pediatric acute lymphoblastic leukemia
Grantee:José Andrés Yunes
Support Opportunities: Regular Research Grants