Epigenetic therapies by targeting aberrant histone methylome in AML: molecular mechanisms, current preclinical and clinical development

Targeting Aberrant Epigenetic Networks Mediated by PRMT1 and KDM4C in Acute Myeloid Leukemia

(2016) Ngai Cheung et al.   CANCER CELL

Jmjd2/Kdm4 demethylases are required for expression ofIl3raand survival of acute myeloid leukemia cells

(2016) Karl Agger et al.   GENES & DEVELOPMENT

MLL-AF9– and HOXA9-mediated acute myeloid leukemia stem cell self-renewal requires JMJD1C

(2016) Nan Zhu et al.   JOURNAL OF CLINICAL INVESTIGATION

BAP1/ASXL1 recruitment and activation for H2A deubiquitination

(2016) Danny D. Sahtoe et al.   Nature Communications

Azacitidine in AML: a treatment option?

(2015) G. Huls   BLOOD

Ezh2 loss in hematopoietic stem cells predisposes mice to develop heterogeneous malignancies in an Ezh1-dependent manner

(2015) M. Mochizuki-Kashio et al.   BLOOD

International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts

(2015) H. Dombret et al.   BLOOD

Epigenetics and approaches to targeted epigenetic therapy in acute myeloid leukemia

(2015) B. J. Wouters et al.   BLOOD

The H3K4-Methyl Epigenome Regulates Leukemia Stem Cell Oncogenic Potential

(2015) Stephen H.K. Wong et al.   CANCER CELL

Inactivation of Eed impedes MLL-AF9–mediated leukemogenesis through Cdkn2a-dependent and Cdkn2a-independent mechanisms in a murine model

(2015) Etienne Danis et al.   EXPERIMENTAL HEMATOLOGY

JMJD1C is required for the survival of acute myeloid leukemia by functioning as a coactivator for key transcription factors

(2015) Mo Chen et al.   GENES & DEVELOPMENT

Transcriptional plasticity promotes primary and acquired resistance to BET inhibition

(2015) Philipp Rathert et al.   NATURE

BET inhibitor resistance emerges from leukaemia stem cells

(2015) Chun Yew Fong et al.   NATURE

DOT1L inhibits SIRT1-mediated epigenetic silencing to maintain leukemic gene expression in MLL-rearranged leukemia

(2015) Chun-Wei Chen et al.   NATURE MEDICINE

Overcoming treatment resistance in acute promyelocytic leukemia and beyond

(2015) Tsz Kan Fung et al.   Oncotarget

shRNA screening identifies JMJD1C as being required for leukemia maintenance

(2014) P. Sroczynska et al.   BLOOD

Selective inhibition of EZH2 and EZH1 enzymatic activity by a small molecule suppresses MLL-rearranged leukemia

(2014) B. Xu et al.   BLOOD

A phase 1 clinical trial of vorinostat in combination with decitabine in patients with acute myeloid leukaemia or myelodysplastic syndrome

(2014) Mark Kirschbaum et al.   BRITISH JOURNAL OF HAEMATOLOGY

Clinical development of demethylating agents in hematology

(2014) Shyamala C. Navada et al.   JOURNAL OF CLINICAL INVESTIGATION

Highly effective combination of LSD1 (KDM1A) antagonist and pan-histone deacetylase inhibitor against human AML cells

(2014) W Fiskus et al.   LEUKEMIA

Chromatin modifiers and the promise of epigenetic therapy in acute leukemia

(2014) S M Greenblatt et al.   LEUKEMIA

Targeting MLL1 H3K4 Methyltransferase Activity in Mixed-Lineage Leukemia

(2014) Fang Cao et al.   MOLECULAR CELL

Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia

(2014) Liran I. Shlush et al.   NATURE

Ezh2 loss promotes development of myelodysplastic syndrome but attenuates its predisposition to leukaemic transformation

(2014) Goro Sashida et al.   Nature Communications

Potent inhibition of DOT1L as treatment of MLL-fusion leukemia

(2013) S. R. Daigle et al.   BLOOD

Leukemic transformation by the MLL-AF6 fusion oncogene requires the H3K79 methyltransferase Dot1l

(2013) A. J. Deshpande et al.   BLOOD

Clonal evolution in relapsed NPM1-mutated acute myeloid leukemia

(2013) J. Kronke et al.   BLOOD

The Histone Demethylase PHF8 Governs Retinoic Acid Response in Acute Promyelocytic Leukemia

(2013) Maria Francisca Arteaga et al.   CANCER CELL

Intoxications with the monoamine oxidase inhibitor tranylcypromine: An analysis of fatal and non-fatal events

(2013) Maximilian Gahr et al.   EUROPEAN NEUROPSYCHOPHARMACOLOGY

Concurrent loss of Ezh2 and Tet2 cooperates in the pathogenesis of myelodysplastic disorders

(2013) Tomoya Muto et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Deletion of Asxl1 results in myelodysplasia and severe developmental defects in vivo

(2013) Omar Abdel-Wahab et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Acute myeloid leukaemia in adults

(2013) Felicetto Ferrara et al.   LANCET

The MLL recombinome of acute leukemias in 2013

(2013) C Meyer et al.   LEUKEMIA

Targeted disruption of the EZH2–EED complex inhibits EZH2-dependent cancer

(2013) Woojin Kim et al.   Nature Chemical Biology

PRMT1 interacts with AML1-ETO to promote its transcriptional activation and progenitor cell proliferative potential

(2012) W.-J. Shia et al.   BLOOD

SnapShot: Acute Myeloid Leukemia

(2012) Bernd B. Zeisig et al.   CANCER CELL

The Histone Demethylase KDM1A Sustains the Oncogenic Potential of MLL-AF9 Leukemia Stem Cells

(2012) William J. Harris et al.   CANCER CELL

ASXL1 Mutations Promote Myeloid Transformation through Loss of PRC2-Mediated Gene Repression

(2012) Omar Abdel-Wahab et al.   CANCER CELL

Phase II Trial of Vorinostat With Idarubicin and Cytarabine for Patients With Newly Diagnosed Acute Myelogenous Leukemia or Myelodysplastic Syndrome

(2012) Guillermo Garcia-Manero et al.   JOURNAL OF CLINICAL ONCOLOGY

EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations

(2012) Michael T. McCabe et al.   NATURE

Inhibition of the LSD1 (KDM1A) demethylase reactivates the all-trans-retinoic acid differentiation pathway in acute myeloid leukemia

(2012) Tino Schenk et al.   NATURE MEDICINE

Polycomb repressive complex 2 is required for MLL-AF9 leukemia

(2012) T. Neff et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Loss of the Tumor Suppressor BAP1 Causes Myeloid Transformation

(2012) A. Dey et al.   SCIENCE

Frequent deletions of JARID2 in leukemic transformation of chronic myeloid malignancies

(2011) Ana Puda et al.   AMERICAN JOURNAL OF HEMATOLOGY

DNMT3A mutations in acute myeloid leukemia: stability during disease evolution and clinical implications

(2011) H.-A. Hou et al.   BLOOD

DOT1L, the H3K79 methyltransferase, is required for MLL-AF9-mediated leukemogenesis

(2011) A. T. Nguyen et al.   BLOOD

The histone methyltransferase inhibitor, DZNep, up-regulates TXNIP, increases ROS production, and targets leukemia cells in AML

(2011) J. Zhou et al.   BLOOD

KDM2b/JHDM1b, an H3K36me2-specific demethylase, is required for initiation and maintenance of acute myeloid leukemia

(2011) J. He et al.   BLOOD

Selective Killing of Mixed Lineage Leukemia Cells by a Potent Small-Molecule DOT1L Inhibitor

(2011) Scott R. Daigle et al.   CANCER CELL

MLL-Rearranged Leukemia Is Dependent on Aberrant H3K79 Methylation by DOT1L

(2011) Kathrin M. Bernt et al.   CANCER CELL

Transcriptional and epigenetic networks in haematological malignancy

(2011) Ngai Cheung et al.   FEBS LETTERS

Acquired mutations in ASXL1 in acute myeloid leukemia: prevalence and prognostic value

(2011) M. Pratcorona et al.   HAEMATOLOGICA

Therapeutic Advances in Acute Myeloid Leukemia

(2011) Alan Burnett et al.   JOURNAL OF CLINICAL ONCOLOGY

RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia

(2011) Johannes Zuber et al.   NATURE

Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia

(2011) Mark A. Dawson et al.   NATURE

Histone H3 Lysine 79 Methyltransferase Dot1 Is Required for Immortalization by MLL Oncogenes

(2010) M.-J. Chang et al.   CANCER RESEARCH

Histone deacetylase inhibitors for the treatment of myelodysplastic syndrome and acute myeloid leukemia

(2010) A Quintás-Cardama et al.   LEUKEMIA

Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin

(2010) Ryan D Morin et al.   NATURE GENETICS

Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders

(2010) Thomas Ernst et al.   NATURE GENETICS

Reconstructing the Disease Model and Epigenetic Networks for MLL-AF4 Leukemia

(2008) Bernd B. Zeisig et al.   CANCER CELL

Aberrant chromatin at genes encoding stem cell regulators in human mixed-lineage leukemia

(2008) M. G. Guenther et al.   GENES & DEVELOPMENT