, Relations entre le taux de 5mC, 5hmC et pronostic des patients : utilité comme biomarqueur ? Plusieurs études ont reliées l'état de méthylation de l'ADN au pronostic des patients. Nous avons donc recherché si des variations significatives de 5mC et/ou 5hmC existaient entre les différents sous-groupes
, Ces taux plus élevés de 5hmC laissent supposer une dérégulation de la méthylation et déméthylation de l'ADN lorsque le pronostic est défavorable, c'est-à-dire que la cellule leucémique est plus agressive avec un potentiel de réplication plus important. On peut également supposer que cette hyperhydroxyméthylation de l'ADN est liée à une diminution focale des taux de 5mC, Nos résultats montrent une tendance à l'augmentation des taux de 5hmC lorsque le pronostic selon l'ELN est défavorable
Figueroa (67) et ses collaborateurs ont montré qu'il existe des ,
, Acute Myeloid Leukemia -Cancer Stat Facts, 2019.
Acute Myeloid Leukemia, N Engl J Med, vol.373, issue.12, pp.1136-52, 2015. ,
Age-related clonal hematopoiesis, Blood, vol.131, issue.5, pp.496-504, 201801. ,
L'hématopoïèse clonale : un concept émergent à la croisée des spécialités. Rev Médecine Interne, 2019. ,
Prognostic Relevance of Integrated Genetic Profiling in Acute Myeloid Leukemia, N Engl J Med, vol.366, issue.12, pp.1079-89, 2012. ,
, Genomic and Epigenomic Landscapes of Adult De Novo Acute Myeloid Leukemia, N Engl J Med, vol.368, issue.22, pp.2059-74, 2013.
Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel, vol.129, pp.424-471, 2017. ,
How I treat hyperleukocytosis in acute myeloid leukemia, Blood, vol.125, issue.21, pp.3246-52, 2015. ,
Approche critique des critères diagnostiques de coagulation intravasculaire disséminée. Réanimation, vol.17, pp.348-54, 2008. ,
Acute myeloid leukemia: A focus on risk factors, clinical presentation, diagnosis and possible lines of management, vol.5, pp.62-69, 2017. ,
Immunophenotyping of acute leukemia and lymphoproliferative disorders: a consensus proposal of the European LeukemiaNet Work Package 10, Leukemia, vol.25, issue.4, pp.567-74, 2011. ,
Place de la cytogénétique dans la prise en charge des leucémies aiguës myéloïdes : actualisation par le Groupe francophone de cytogénétique hématologique (GFCH), An Biol Clin, vol.74, issue.5, pp.535-581, 2016. ,
The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia, Blood, vol.127, issue.20, pp.2391-405, 2016. ,
Diagnosis and management of acute myeloid leukemia in children and adolescents: recommendations from an international expert panel, Blood, vol.120, issue.16, pp.3187-205, 2012. ,
Implication des mutations des gènes IDH1 et IDH2 dans les leucémies aiguës myéloïdes. Hématologie, vol.17, pp.132-176, 2011. ,
Genomic Classification and Prognosis in Acute Myeloid Leukemia, N Engl J Med, vol.374, issue.23, pp.2209-2230, 2009. ,
How I treat acute myeloid leukemia, Blood, vol.116, issue.17, pp.3147-56, 2010. ,
How I treat the older patient with acute myeloid leukemia, Blood, vol.125, issue.5, pp.767-74, 2015. ,
Long-term efficacy and safety of all-trans retinoic acid/arsenic trioxide-based therapy in newly diagnosed acute promyelocytic leukemia, Proc Natl Acad Sci, vol.106, issue.9, pp.3342-3349, 2009. ,
Addition of gemtuzumab ozogamicin to induction chemotherapy in adult patients with acute myeloid leukaemia: a meta-analysis of individual patient data from randomised controlled trials, Lancet Oncol, vol.15, issue.9, pp.986-96, 2014. ,
Molecular biomarkers in acute myeloid leukemia, Blood Rev, vol.31, issue.1, pp.63-76, 2017. ,
DNA methylation: roles in mammalian developmen, Nat Rev Genet, issue.14, pp.204-224, 2013. ,
Cytosine modifications in myeloid malignancies, Pharmacol Ther, vol.152, pp.42-53, 2015. ,
Epigenetic Function of TET Family, 5-Methylcytosine, and 5-Hydroxymethylcytosine in Hematologic Malignancies, Oncol Res Treat, vol.42, issue.6, pp.309-327, 2019. ,
DNA Methylation and Cancer, Advances in Genetics, pp.27-56, 2010. ,
5-hydroxymethylcytosine in cancer: significance in diagnosis and therapy, Cancer Genet, vol.208, issue.5, pp.167-77, 2015. ,
DNA methylation and cancer, J Clin Oncol Off J Am Soc Clin Oncol, vol.22, issue.22, pp.4632-4674, 2004. ,
Hydroxymethylcytosine (5hmC), or How to Identify Your Favorite Cell. Epigenomes, Jan, vol.5, issue.1, p.3, 2018. ,
Tissue type is a major modifier of the 5-hydroxymethylcytosine content of human genes, Genome Res, vol.22, issue.3, pp.467-77, 2012. ,
Tet1 is dispensable for maintaining pluripotency and its loss is compatible with embryonic and postnatal development, Cell Stem Cell, vol.9, issue.2, pp.166-75, 2011. ,
Inhibition of TET2-mediated conversion of 5-methylcytosine to 5-hydroxymethylcytosine disturbs erythroid and granulomonocytic differentiation of human hematopoietic progenitors, Blood, vol.118, issue.9, pp.2551-2556, 2011. ,
The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes, Nature, vol.477, issue.7366, pp.606-616, 2011. ,
Clinical impact of DNMT3A mutations in younger adult patients with acute myeloid leukemia: results of the AML Study Group (AMLSG), Blood, vol.121, issue.23, pp.4769-77, 2013. ,
Cancer-associated metabolite 2-hydroxyglutarate accumulates in acute myelogenous leukemia with isocitrate dehydrogenase 1 and 2 mutations, J Exp Med, vol.207, issue.2, pp.339-383, 2010. ,
Landscape of TET2 mutations in acute myeloid leukemia, Leukemia, vol.26, issue.5, pp.934-976, 2012. ,
TET1 plays an essential oncogenic role in MLLrearranged leukemia, Proc Natl Acad Sci, vol.110, issue.29, pp.11994-12003, 2013. ,
Leukemic IDH1 and IDH2 Mutations Result in a Hypermethylation Phenotype, Disrupt TET2 Function, and Impair Hematopoietic Differentiation. Cancer Cell, vol.18, pp.553-67, 2010. ,
DNA Hydroxymethylation Profiling Reveals that WT1 Mutations Result in Loss of TET2 Function in Acute Myeloid Leukemia, Cell Rep, vol.9, issue.5, pp.1841-55, 2014. ,
Myelodysplastic syndromes: 2018 update on diagnosis, risk-stratification and management, Am J Hematol, vol.93, issue.1, pp.129-176, 2017. ,
The hypomethylating agent Decitabine causes a paradoxical increase in 5-hydroxymethylcytosine in human leukemia cells. Sci Rep, vol.5, p.9281, 2015. ,
Inhibition of DNA methyltransferase leads to increased genomic 5-hydroxymethylcytosine levels in hematopoietic cells, FEBS Open Bio, vol.8, issue.4, pp.584-92, 2018. ,
Impact of TET2 mutations on response rate to azacitidine in myelodysplastic syndromes and low blast count acute myeloid leukemias, Leukemia, vol.25, issue.7, pp.1147-52, 2011. ,
, N°4 Déc. 2018 : leucémies aiguës myéloblastiques(LAM) Inhibiteurs d'IDH1, vol.8
, , 2018.
, IDHIFA 50 mg, comprimé -ANSM : Agence nationale de sécurité du médicament et des produits de santé, 2019.
, Métabolisme du fer chez l'Homme, laboratoire d'hématologie cellulaire du CHU d'Angers
Hepcidin: A novel peptide hormone regulating iron metabolism, Clin Chim Acta, vol.412, issue.11, pp.823-853, 2011. ,
Dyserythropoiesis evaluated by the RED score and hepcidin:ferritin ratio predicts response to erythropoietin in lower-risk myelodysplastic syndromes, Haematologica, vol.104, issue.3, pp.497-504, 2019. ,
Rôle du fer et des espèces réactives de l'oxygène dans la prolifération et la différenciation des leucémies aiguës myéloblastiques, 2013. ,
Tuning Cell Cycle Regulation with an Iron Key. Cell Cycle, vol.6, pp.1982-94, 2007. ,
TET proteins and the control of cytosine demethylation in cancer, Genome Med, vol.7, issue.1, p.9, 2015. ,
Nickel(II) Inhibits Tet-Mediated 5-Methylcytosine Oxidation by High Affinity Displacement of the Cofactor Iron(II), ACS Chem Biol, vol.12, issue.6, pp.1494-1502, 2017. ,
, , 2019.
Cycle cellulaire et cytométrie en flux ,
Real-time quantitative polymerase chain reaction detection of minimal residual disease by standardized WT1 assay to enhance risk stratification in acute myeloid leukemia: a European LeukemiaNet study, J Clin Oncol Off J Am Soc Clin Oncol, vol.27, issue.31, pp.5195-201, 2009. ,
, , 2019.
The role of iron in cell cycle progression and the proliferation of neoplastic cells, Biochim Biophys Acta BBA -Rev Cancer, vol.1603, issue.1, pp.31-46, 2002. ,
Global Methylome of Normal and Malignant Hematopoietic Stem Cells. Blood, vol.110, pp.2118-2118, 2007. ,
Profiles of a broad spectrum of epigenetic DNA modifications in normal and malignant human cell lines: Proliferation rate is not the major factor responsible for the 5-hydroxymethyl-2?-deoxycytidine level in cultured cancerous cell lines. PLOS ONE, vol.12, p.188856, 2017. ,
The Role of Deferiprone in Iron Chelation, N Engl J Med, vol.379, issue.22, pp.2140-50, 2018. ,
Ferric ammonium citrate, 2019. ,
Distribution of 5-Hydroxymethylcytosine in Different Human Tissues, Journal of Nucleic Acids, 2011. ,
Characterization of acute myeloid leukemia based on levels of global hydroxymethylation, Blood, vol.124, issue.7, pp.1110-1118, 2014. ,
5-Hydroxymethylcytosine correlates with epigenetic regulatory mutations, but may not have prognostic value in predicting survival in normal karyotype acute myeloid leukemia, Oncotarget, vol.8, issue.5, pp.8305-8319, 2016. ,
, , 2019.
Cytosine 5-hydroxymethylation regulated kit gene expression in acute myeloid leukemia, J Biol Regul Homeost Agents, vol.33, issue.2, pp.345-53, 2019. ,
The R882H DNMT3A Mutation Associated with AML Dominantly Inhibits Wild-Type DNMT3A by Blocking Its Ability to Form Active Tetramers, Cancer Cell, vol.25, issue.4, pp.442-54, 2014. ,
DNA Methylation Signatures Identify Biologically Distinct Subtypes in Acute Myeloid Leukemia. Cancer Cell, vol.17, pp.13-27, 2010. ,