scholarly journals Ubiquitin and SUMO conjugation as biomarkers of acute myeloid leukemias response to chemotherapies

2020 ◽  
Vol 3 (6) ◽  
pp. e201900577 ◽  
Author(s):  
Pierre Gâtel ◽  
Frédérique Brockly ◽  
Christelle Reynes ◽  
Manuela Pastore ◽  
Yosr Hicheri ◽  
...  
Keyword(s):  
Cancer Patient ◽  
Standard Chemotherapy ◽  
Protein Arrays ◽  
Patient Response ◽  
Sumo Conjugation ◽  
Cell Extracts ◽  
Myeloid Leukemias ◽  
New Type ◽  
Acute Myeloid ◽  
Patient Cell

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.

scholarly journals Ubiquitin and SUMO conjugation as biomarkers of Acute Myeloid Leukemias response to chemotherapies

2019 ◽  
Author(s):  
Pierre Gâtel ◽  
Frédérique Brockly ◽  
Christelle Reynes ◽  
Manuela Pastore ◽  
Yosr Hicheri ◽  
...  
Keyword(s):  
Protein Modification ◽  
Standard Chemotherapy ◽  
Patient Response ◽  
New Class ◽  
Sumo Conjugation ◽  
Cell Extracts ◽  
Myeloid Leukemias ◽  
New Type ◽  
Acute Myeloid ◽  
Patient Cell

AbstractUbiquitin 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 cells 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 (daunorubicine-DNR and cytarabine-Ara-C). We compared the ability of extracts from chemosensitive and chemoresistant AML cells to conjugate ubiquitin or SUMO-1 on 9000 proteins spotted on protein-arrays. We identified 122 proteins whose conjugation by these post-translational modifiers marks AML resistance to DNR and/or Ara-C. Based on this modifomic signature, we defined a statistical score able to predict AML patient response to standard chemotherapy. We finally developed a miniaturized assay to easily assess the modification level 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 patients response to treatments.Summary blurbThis study describes the identification of a new class of biomarkers of cancer response to therapies based on protein modification by Ubiquitin and SUMO and provides the tools to analyze them in Acute Myeloid Leukemia patient samples.

Expression pattern of the septin gene family in acute myeloid leukemias with and without MLL-SEPT fusion genes

2010 ◽  
Vol 34 (5) ◽  
pp. 615-621 ◽  
Author(s):  
Joana Santos ◽  
Nuno Cerveira ◽  
Susana Bizarro ◽  
Franclim R. Ribeiro ◽  
Cecília Correia ◽  
...  
Keyword(s):  
Gene Family ◽  
Expression Pattern ◽  
Fusion Genes ◽  
Myeloid Leukemias ◽  
Acute Myeloid

The clinical characteristics of CD7+ CD56+ acute myeloid leukemias other than M0

2010 ◽  
Vol 91 (2) ◽  
pp. 303-309 ◽  
Author(s):  
Ritsuro Suzuki ◽  
Shigeki Ohtake ◽  
Jin Takeuchi ◽  
Masami Nagai ◽  
Yoshihisa Kodera ◽  
...  
Keyword(s):  
Clinical Characteristics ◽  
Myeloid Leukemias ◽  
Acute Myeloid

scholarly journals Isocitrate dehydrogenase 1 and 2 mutations, 2‐hydroxyglutarate levels, and response to standard chemotherapy for patients with newly diagnosed acute myeloid leukemia

Cancer ◽  
2018 ◽  
Vol 125 (4) ◽  
pp. 541-549 ◽  
Author(s):  
Andrew M. Brunner ◽  
Donna S. Neuberg ◽  
Seth A. Wander ◽  
Hossein Sadrzadeh ◽  
Karen K. Ballen ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Isocitrate Dehydrogenase ◽  
Myeloid Leukemia ◽  
Newly Diagnosed ◽  
Standard Chemotherapy ◽  
Isocitrate Dehydrogenase 1 ◽  
Acute Myeloid

Sequential Combination of Gemtuzumab Ozogamicin and Standard Chemotherapy in Older Patients With Newly Diagnosed Acute Myeloid Leukemia: Results of a Randomized Phase III Trial by the EORTC and GIMEMA Consortium (AML-17)

2013 ◽  
Vol 31 (35) ◽  
pp. 4424-4430 ◽  
Author(s):  
Sergio Amadori ◽  
Stefan Suciu ◽  
Roberto Stasi ◽  
Helmut R. Salih ◽  
Dominik Selleslag ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Gemtuzumab Ozogamicin ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Standard Chemotherapy ◽  
Sequential Combination ◽  
Grade 3 ◽  
Acute Myeloid

Purpose This randomized trial evaluated the efficacy and toxicity of sequential gemtuzumab ozogamicin (GO) and standard chemotherapy in older patients with newly diagnosed acute myeloid leukemia (AML). Patients and Methods Patients (n = 472) age 61 to 75 years were randomly assigned to induction chemotherapy with mitoxantrone, cytarabine, and etoposide preceded, or not, by a course of GO (6 mg/m2 on days 1 and 15). In remission, patients received two consolidation courses with or without GO (3 mg/m2 on day 0). The primary end point was overall survival (OS). Results The overall response rate was comparable between the two arms (GO, 45%; no GO, 49%), but induction and 60-day mortality rates were higher in the GO arm (17% v 12% and 22% v 18%, respectively). With median follow-up of 5.2 years, median OS was 7.1 months in the GO arm and 10 months in the no-GO arm (hazard ratio, 1.20; 95% CI, 0.99 to 1.45; P = .07). Other survival end points were similar in both arms. Grade 3 to 4 hematologic and liver toxicities were greater in the GO arm. Treatment with GO provided no benefit in any prognostic subgroup, with the possible exception of patients age < 70 years with secondary AML, but outcomes were significantly worse in the oldest age subgroup because of a higher risk of early mortality. Conclusion As used in this trial, the sequential combination of GO and standard chemotherapy provides no benefit for older patients with AML and is too toxic for those age ≥ 70 years.

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