RT Journal Article
SR Electronic
T1 Ubiquitin and SUMO conjugation as biomarkers of acute myeloid leukemias response to chemotherapies
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e201900577
DO 10.26508/lsa.201900577
VO 3
IS 6
A1 Pierre Gâtel
A1 Frédérique Brockly
A1 Christelle Reynes
A1 Manuela Pastore
A1 Yosr Hicheri
A1 Guillaume Cartron
A1 Marc Piechaczyk
A1 Guillaume Bossis
YR 2020
UL https://www.life-science-alliance.org/content/3/6/e201900577.abstract
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.