التفاصيل البيبلوغرافية
| العنوان: |
Data from Targeting the SUMO Pathway Primes All-trans Retinoic Acid–Induced Differentiation of Nonpromyelocytic Acute Myeloid Leukemias |
| المؤلفون: |
Guillaume Bossis, Marc Piechaczyk, Guillaume Cartron, Yosr Hicheri, Jean-Emmanuel Sarry, Tamara Salem, Sonia Zaghdoudi, Julie Kowalczyk, Mohsen Hosseini, Mathias Boulanger, Hayeon Baik |
| بيانات النشر: |
American Association for Cancer Research (AACR), 2023. |
| سنة النشر: |
2023 |
| الوصف: |
Differentiation therapies using all-trans retinoic acid (ATRA) are highly efficient at treating acute promyelocytic leukemia (APL), a subtype of acute myeloid leukemia (AML). However, their efficacy, if any, is limited in the case of non-APL AML. We report here that inhibition of SUMOylation, a posttranslational modification related to ubiquitination, restores the prodifferentiation and antiproliferative activities of retinoids in non-APL AML. Controlled inhibition of SUMOylation with the pharmacologic inhibitors 2-D08 or anacardic acid, or via overexpression of SENP deSUMOylases, enhanced the ATRA-induced expression of key genes involved in differentiation, proliferation, and apoptosis in non-APL AML cells. This activated ATRA-induced terminal myeloid differentiation and reduced cell proliferation and viability, including in AML cells resistant to chemotherapeutic drugs. Conversely, enhancement of SUMOylation via overexpression of the SUMO-conjugating enzyme Ubc9 dampened expression of ATRA-responsive genes and prevented differentiation. Thus, inhibition of the SUMO pathway is a promising strategy to sensitize patients with non-APL AML to retinoids and improve the treatment of this poor-prognosis cancer.Significance: SUMOylation silences key ATRA-responsive genes in nonpromyelocytic acute myeloid leukemias. Cancer Res; 78(10); 2601–13. ©2018 AACR. |
| URL الوصول: |
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1e425d78d860ad85cdb8c00f13e92307
https://doi.org/10.1158/0008-5472.c.6510477.v1 |
| حقوق: |
OPEN |
| رقم الأكسشن: |
edsair.doi.dedup.....1e425d78d860ad85cdb8c00f13e92307 |
| قاعدة البيانات: |
OpenAIRE |
