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.

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 A novel class of zinc finger/leucine zipper genes identified from the molecular cloning of the t(10;11) translocation in acute leukemia

Blood ◽  
1995 ◽  
Vol 85 (6) ◽  
pp. 1435-1441 ◽  
Author(s):  
T Chaplin ◽  
P Ayton ◽  
OA Bernard ◽  
V Saha ◽  
V Della Valle ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Acute Leukemia ◽  
Molecular Cloning ◽  
Zinc Finger ◽  
Leucine Zipper ◽  
Chromosomal Translocation ◽  
New Class ◽  
Myeloid Leukemias ◽  
Zinc Finger Region ◽  
Acute Myeloid

A novel class of conserved transcription factors has been identified from the molecular cloning of AF10, the gene involved in the t(10;11)(p12;q23) translocation of acute myeloid leukemias. AF10 encodes a 109-kD protein of 1,027 amino acids and contains an N- terminal zinc finger region and a C-terminal leucine zipper. These structures have been found to be conserved in sequence and position in three other proteins, AF17, BR140, and a previously unrecognized Caenorhabditis elegans gene, provisionally named CEZF. The overall structure, level of sequence conservation, and expression pattern suggest that these genes encode a new class of transcription factors, some of which are targets for chromosomal translocation in acute leukemia.

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

Theoretical Studies of the Physical Properties of Rodlike and Related Polymers

1988 ◽  
Vol 134 ◽  
Author(s):  
W. J. Welsh ◽  
J. E. Mark ◽  
Y. Yang ◽  
G. P. Das
Keyword(s):  
High Performance ◽  
Liquid Crystalline ◽  
Theoretical Work ◽  
Environmental Resistance ◽  
New Class ◽  
Protonated Forms ◽  
New Type ◽  
Electrooptical Properties ◽  
Cis And Trans ◽  
Strong Acids

ABSTRACTThis review focuses on a new type of para-catenated aromatic polymer being used in the preparation of high-performance films and fibers of exceptional strength, thermal stability, and environmental resistance, including inertness to essentially all common solvents. Polymers of this type include the cis- and trans-poly(p-phenylene benzobisoxazole) (PBO), the cis- and trans-forms of the corresponding poly(pphenylene benzobisthiazole) (PBT), and the structurally similar poly(5,5ʹ-bibenzoxazole-2.2ʹ-diyl-l,3-phenylene) (AAPBO) and poly(2,5-benzoxazole) (ABPBO) and their sulfurcontaining analogues. Because of their rigidity, these polymers become highly oriented in solution and some display liquid crystalline behavior. The purpose of this paper is to summarize the authorsʹ theoretical work on the structures, conformational energies, intermolecular interactions, electronic properties, electrical conductivity, and electrooptical properties of these chains, including, in some cases, the so-called articulated forms and the protonated forms known to exist in strong acids. The emphasis is on how such studies provide a molecular understanding of the unusual properties and processing characteristics of this new class of materials.

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