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

Autor:	Sugita M; Department of Medicine, Division of Hematology/Oncology, Weill Cornell Medicine, New York, NY, USA., Wilkes DC; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine and NewYork Presbyterian, New York, NY, USA.; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA., Bareja R; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine and NewYork Presbyterian, New York, NY, USA.; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.; Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA., Eng KW; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine and NewYork Presbyterian, New York, NY, USA.; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.; Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA., Nataraj S; Department of Medicine, Division of Hematology/Oncology, Weill Cornell Medicine, New York, NY, USA., Jimenez-Flores RA; Department of Medicine, Division of Hematology/Oncology, Weill Cornell Medicine, New York, NY, USA., Yan L; Department of Medicine, Division of Hematology/Oncology, Weill Cornell Medicine, New York, NY, USA., De Leon JP; Department of Medicine, Division of Hematology/Oncology, Weill Cornell Medicine, New York, NY, USA., Croyle JA; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine and NewYork Presbyterian, New York, NY, USA., Kaner J; Department of Medicine, Division of Hematology/Oncology, Weill Cornell Medicine, New York, NY, USA., Merugu S; Department of Medicine, Division of Hematology/Oncology, Weill Cornell Medicine, New York, NY, USA.; Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Sharma S; Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA., MacDonald TY; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine and NewYork Presbyterian, New York, NY, USA., Noorzad Z; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine and NewYork Presbyterian, New York, NY, USA., Panchal P; Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Pancirer D; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine and NewYork Presbyterian, New York, NY, USA., Cheng S; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine and NewYork Presbyterian, New York, NY, USA., Xiang JZ; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine and NewYork Presbyterian, New York, NY, USA., Olson L; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA., Van Besien K; Department of Medicine, Division of Hematology/Oncology, Weill Cornell Medicine, New York, NY, USA.; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine and NewYork Presbyterian, New York, NY, USA., Rickman DS; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine and NewYork Presbyterian, New York, NY, USA.; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA., Mathew S; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA., Tam W; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA., Rubin MA; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine and NewYork Presbyterian, New York, NY, USA.; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.; Bern Center of Precision Medicine, Universität of Bern, Bern, Switzerland., Beltran H; Department of Medicine, Division of Hematology/Oncology, Weill Cornell Medicine, New York, NY, USA.; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine and NewYork Presbyterian, New York, NY, USA.; Division of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA., Sboner A; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine and NewYork Presbyterian, New York, NY, USA.; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA., Hassane DC; Department of Medicine, Division of Hematology/Oncology, Weill Cornell Medicine, New York, NY, USA., Chiosis G; Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Elemento O; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine and NewYork Presbyterian, New York, NY, USA.; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.; Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA., Roboz GJ; Department of Medicine, Division of Hematology/Oncology, Weill Cornell Medicine, New York, NY, USA.; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine and NewYork Presbyterian, New York, NY, USA., Mosquera JM; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine and NewYork Presbyterian, New York, NY, USA. jmm9018@med.cornell.edu.; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA. jmm9018@med.cornell.edu., Guzman ML; Department of Medicine, Division of Hematology/Oncology, Weill Cornell Medicine, New York, NY, USA. mlg2007@med.cornell.edu.; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine and NewYork Presbyterian, New York, NY, USA. mlg2007@med.cornell.edu.; Department of Pharmacology, Weill Cornell Medicine, New York, NY, USA. mlg2007@med.cornell.edu.
Jazyk:	angličtina
Zdroj:	NPJ precision oncology [NPJ Precis Oncol] 2021 May 26; Vol. 5 (1), pp. 44. Date of Electronic Publication: 2021 May 26.
DOI:	10.1038/s41698-021-00183-2
Abstrakt:	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.
Databáze:	MEDLINE
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