PT  - JOURNAL ARTICLE
AU  - Pierre Gâtel
AU  - Frédérique Brockly
AU  - Christelle Reynes
AU  - Manuela Pastore
AU  - Yosr Hicheri
AU  - Guillaume Cartron
AU  - Marc Piechaczyk
AU  - Guillaume Bossis
TI  - Ubiquitin and SUMO conjugation as biomarkers of acute myeloid leukemias response to chemotherapies
AID  - 10.26508/lsa.201900577
DP  - 2020 Jun 01
TA  - Life Science Alliance
PG  - e201900577
VI  - 3
IP  - 6
4099  - https://www.life-science-alliance.org/content/3/6/e201900577.short
4100  - https://www.life-science-alliance.org/content/3/6/e201900577.full
SO  - Life Sci. Alliance2020 Jun 01; 3
AB  - Ubiquitin and the ubiquitin-like SUMO are covalently conjugated to thousands of proteins to modulate their function and fate. Many of the enzymes involved in their conjugation are dysregulated in cancers and involved in cancer cell response to therapies. We describe here the identification of biomarkers of the activity of these enzymes and their use to predict acute myeloid leukemias (AML) response to standard chemotherapy (daunorubicin-DNR and cytarabine-Ara-C). We compared the ability of extracts from chemosensitive and chemoresistant AML cells to conjugate ubiquitin or SUMO-1 on 9,000 proteins spotted on protein arrays. We identified 122 proteins whose conjugation by these posttranslational modifiers marks AML resistance to DNR and/or Ara-C. Based on this signature, we defined a statistical score predicting AML patient response to standard chemotherapy. We finally developed a miniaturized assay allowing for easy assessment of modification levels of the selected biomarkers and validated it in patient cell extracts. Thus, our work identifies a new type of ubiquitin-based biomarkers that could be used to predict cancer patient response to treatments.