Targeting the epichaperome as an effective precision medicine approach in a novel PML-SYK fusion acute myeloid leukemia
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 monitor...
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Nature Portfolio
2021
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oai:doaj.org-article:9b26f08bf6d444edb5f3140c7fcddf4c2021-12-02T15:49:33ZTargeting the epichaperome as an effective precision medicine approach in a novel PML-SYK fusion acute myeloid leukemia10.1038/s41698-021-00183-22397-768Xhttps://doaj.org/article/9b26f08bf6d444edb5f3140c7fcddf4c2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41698-021-00183-2https://doaj.org/toc/2397-768XAbstract 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.Mayumi SugitaDavid C. WilkesRohan BarejaKenneth W. EngSarah NatarajReyna A. Jimenez-FloresLunBiao YanJeanne Pauline De LeonJaclyn A. CroyleJustin KanerSwathi MeruguSahil SharmaTheresa Y. MacDonaldZohal NoorzadPalak PanchalDanielle PancirerShuhua ChengJenny Z. XiangLuke OlsonKoen Van BesienDavid S. RickmanSusan MathewWayne TamMark A. RubinHimisha BeltranAndrea SbonerDuane C. HassaneGabriela ChiosisOlivier ElementoGail J. RobozJuan Miguel MosqueraMonica L. GuzmanNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Precision Oncology, Vol 5, Iss 1, Pp 1-10 (2021) |
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DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 |
| spellingShingle |
Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Mayumi Sugita David C. Wilkes Rohan Bareja Kenneth W. Eng Sarah Nataraj Reyna A. Jimenez-Flores LunBiao Yan Jeanne Pauline De Leon Jaclyn A. Croyle Justin Kaner Swathi Merugu Sahil Sharma Theresa Y. MacDonald Zohal Noorzad Palak Panchal Danielle Pancirer Shuhua Cheng Jenny Z. Xiang Luke Olson Koen Van Besien David S. Rickman Susan Mathew Wayne Tam Mark A. Rubin Himisha Beltran Andrea Sboner Duane C. Hassane Gabriela Chiosis Olivier Elemento Gail J. Roboz Juan Miguel Mosquera Monica L. Guzman Targeting the epichaperome as an effective precision medicine approach in a novel PML-SYK fusion acute myeloid leukemia |
| description |
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. |
| format |
article |
| author |
Mayumi Sugita David C. Wilkes Rohan Bareja Kenneth W. Eng Sarah Nataraj Reyna A. Jimenez-Flores LunBiao Yan Jeanne Pauline De Leon Jaclyn A. Croyle Justin Kaner Swathi Merugu Sahil Sharma Theresa Y. MacDonald Zohal Noorzad Palak Panchal Danielle Pancirer Shuhua Cheng Jenny Z. Xiang Luke Olson Koen Van Besien David S. Rickman Susan Mathew Wayne Tam Mark A. Rubin Himisha Beltran Andrea Sboner Duane C. Hassane Gabriela Chiosis Olivier Elemento Gail J. Roboz Juan Miguel Mosquera Monica L. Guzman |
| author_facet |
Mayumi Sugita David C. Wilkes Rohan Bareja Kenneth W. Eng Sarah Nataraj Reyna A. Jimenez-Flores LunBiao Yan Jeanne Pauline De Leon Jaclyn A. Croyle Justin Kaner Swathi Merugu Sahil Sharma Theresa Y. MacDonald Zohal Noorzad Palak Panchal Danielle Pancirer Shuhua Cheng Jenny Z. Xiang Luke Olson Koen Van Besien David S. Rickman Susan Mathew Wayne Tam Mark A. Rubin Himisha Beltran Andrea Sboner Duane C. Hassane Gabriela Chiosis Olivier Elemento Gail J. Roboz Juan Miguel Mosquera Monica L. Guzman |
| author_sort |
Mayumi Sugita |
| title |
Targeting the epichaperome as an effective precision medicine approach in a novel PML-SYK fusion acute myeloid leukemia |
| title_short |
Targeting the epichaperome as an effective precision medicine approach in a novel PML-SYK fusion acute myeloid leukemia |
| title_full |
Targeting the epichaperome as an effective precision medicine approach in a novel PML-SYK fusion acute myeloid leukemia |
| title_fullStr |
Targeting the epichaperome as an effective precision medicine approach in a novel PML-SYK fusion acute myeloid leukemia |
| title_full_unstemmed |
Targeting the epichaperome as an effective precision medicine approach in a novel PML-SYK fusion acute myeloid leukemia |
| title_sort |
targeting the epichaperome as an effective precision medicine approach in a novel pml-syk fusion acute myeloid leukemia |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/9b26f08bf6d444edb5f3140c7fcddf4c |
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