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

Autor(es)

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]}

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 10, n. 6 JUN 11 2015.
• Citações Web of Science: 3

Resumo

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)

• Processo FAPESP: 12/12802-1 - Mutações cooperantes, caracterização funcional e anticorpos contra o mutante do IL7R na leucemia linfóide aguda
• Beneficiário: José Andrés Yunes
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 08/10034-1 - Microambiente da medula óssea e PI3K na resistência a drogas da leucemia linfóide aguda pediátrica
• Beneficiário: José Andrés Yunes
• Modalidade de apoio: Auxílio à Pesquisa - Regular