Targeting the epichaperome as an effective precision medicine approach in a novel PML-SYK fusion acute myeloid leukemia.

TitleTargeting the epichaperome as an effective precision medicine approach in a novel PML-SYK fusion acute myeloid leukemia.
Publication TypeJournal Article
Year of Publication2021
AuthorsSugita M, Wilkes DC, Bareja R, Eng KW, Nataraj S, Jimenez-Flores RA, Yan LB, De Leon JPauline, Croyle JA, Kaner J, Merugu S, Sharma S, MacDonald TY, Noorzad Z, Panchal P, Pancirer D, Cheng S, Xiang JZ, Olson L, Van Besien K, Rickman DS, Mathew S, Tam W, Rubin MA, Beltran H, Sboner A, Hassane DC, Chiosis G, Elemento O, Roboz GJ, Mosquera JMiguel, Guzman ML
JournalNPJ Precis Oncol
Volume5
Issue1
Pagination44
Date Published2021 May 26
ISSN2397-768X
Abstract

The epichaperome is a new cancer target composed of hyperconnected networks of chaperome members that facilitate cell survival. Cancers with an altered chaperone configuration may be susceptible to epichaperome inhibitors. We developed a flow cytometry-based assay for evaluation and monitoring of epichaperome abundance at the single cell level, with the goal of prospectively identifying patients likely to respond to epichaperome inhibitors, to measure target engagement, and dependency during treatment. As proof of principle, we describe a patient with an unclassified myeloproliferative neoplasm harboring a novel PML-SYK fusion, who progressed to acute myeloid leukemia despite chemotherapy and allogeneic stem cell transplant. The leukemia was identified as having high epichaperome abundance. We obtained compassionate access to an investigational epichaperome inhibitor, PU-H71. After 16 doses, the patient achieved durable complete remission. These encouraging results suggest that further investigation of epichaperome inhibitors in patients with abundant baseline epichaperome levels is warranted.

DOI10.1038/s41698-021-00183-2
Alternate JournalNPJ Precis Oncol
PubMed ID34040147
PubMed Central IDPMC8155064
Grant ListR01 AG067598 / AG / NIA NIH HHS / United States
R56 AG061869 / AG / NIA NIH HHS / United States
1R01CA234478-01 / / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) /
P50 CA192937 / CA / NCI NIH HHS / United States
R56 AG072599 / AG / NIA NIH HHS / United States
R01 CA234478 / CA / NCI NIH HHS / United States
U01 AG032969 / AG / NIA NIH HHS / United States
P30 CA008748 / CA / NCI NIH HHS / United States
P01 CA186866 / CA / NCI NIH HHS / United States
Related Faculty: 
Andrea Sboner, Ph.D. David Rickman, Ph.D. Juan Miguel Mosquera, M.D. Wayne Tam, M.D., Ph.D.

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