Pathogenic Impacts of Dysregulated Polycomb Repressive Complex Function in Hematological Malignancies

A LYSA Phase Ib Study of tazemetostat (EPZ-6438) plus R-CHOP in newly diagnosed Diffuse Large B Cell Lymphoma (DLBCL) patients with poor prognosis features

(2020) Clémentine Sarkozy et al.   CLINICAL CANCER RESEARCH

ASXL1 mutation in clonal hematopoiesis

(2020) Takeshi Fujino et al.   EXPERIMENTAL HEMATOLOGY

EZH2 deficient T-cell acute lymphoblastic leukemia is sensitized to CHK1 inhibition through enhanced replication stress

(2020) Theresa Elizabeth Leon et al.   Cancer Discovery

Tazemetostat for patients with relapsed or refractory follicular lymphoma: an open-label, single-arm, multicentre, phase 2 trial

(2020) Franck Morschhauser et al.   LANCET ONCOLOGY

Bcor loss perturbs myeloid differentiation and promotes leukaemogenesis

(2019) Madison J. Kelly et al.   Nature Communications

Contrasting requirements during disease evolution identify EZH2 as a therapeutic target in AML

(2019) Faisal Basheer et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Mutant H3 histones drive human pre-leukemic hematopoietic stem cell expansion and promote leukemic aggressiveness

(2019) Meaghan Boileau et al.   Nature Communications

Loss of EZH2 Reprograms BCAA Metabolism to Drive Leukemic Transformation

(2019) Zhimin Gu et al.   Cancer Discovery

Akt Inhibition Synergizes with PRC2 Inhibition in the Treatment of Multiple Myeloma

(2019) Mohamed Rizk et al.   CANCER SCIENCE

Phase 1 study of the novel enhancer of zeste homolog 2 (EZH2) inhibitor GSK2816126 in patients with advanced hematological and solid tumors

(2019) Timothy A. Yap et al.   CLINICAL CANCER RESEARCH

Mechanisms of resistance to EZH2 inhibitors in diffuse large B-cell lymphomas

(2018) Malik Bisserier et al.   BLOOD

Ezh2 and Runx1 Mutations Collaborate to Initiate Lympho-Myeloid Leukemia in Early Thymic Progenitors

(2018) Christopher A.G. Booth et al.   CANCER CELL

Dual Targeting of Oncogenic Activation and Inflammatory Signaling Increases Therapeutic Efficacy in Myeloproliferative Neoplasms

(2018) Maria Kleppe et al.   CANCER CELL

Usefulness of BCOR gene mutation as a prognostic factor in acute myeloid leukemia with intermediate cytogenetic prognosis

(2018) Kazuki Terada et al.   GENES CHROMOSOMES & CANCER

Expression of mutant Asxl1 perturbs hematopoiesis and promotes susceptibility to leukemic transformation

(2018) Reina Nagase et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Tazemetostat, an EZH2 inhibitor, in relapsed or refractory B-cell non-Hodgkin lymphoma and advanced solid tumours: a first-in-human, open-label, phase 1 study

(2018) Antoine Italiano et al.   LANCET ONCOLOGY

Profiling of aberrant DNA methylation in acute myeloid leukemia reveals subclasses of CG-rich regions with epigenetic or genetic association

(2018) Claudia Gebhard et al.   LEUKEMIA

Enhancer of zeste homolog 2 (EZH2) inhibitors

(2018) Nitya Gulati et al.   LEUKEMIA & LYMPHOMA

Mutations in DNMT3A, U2AF1, and EZH2 identify intermediate-risk acute myeloid leukemia patients with poor outcome after CR1

(2018) Caner Saygin et al.   Blood Cancer Journal

Bcor insufficiency promotes initiation and progression of myelodysplastic syndrome

(2018) Shiro Tara et al.   BLOOD

Targeting Epigenetic Crosstalk as a Therapeutic Strategy for EZH2-Aberrant Solid Tumors

(2018) Xun Huang et al.   CELL

Ezh2 loss propagates hypermethylation at T cell differentiation–regulating genes to promote leukemic transformation

(2018) Changshan Wang et al.   JOURNAL OF CLINICAL INVESTIGATION

Pan-cancer genome and transcriptome analyses of 1,699 paediatric leukaemias and solid tumours

(2018) Xiaotu Ma et al.   NATURE

Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation

(2018) Jennifer K. Litton et al.   NEW ENGLAND JOURNAL OF MEDICINE

Dual inhibition of enhancer of zeste homolog 1/2 overactivates WNT signaling to deplete cancer stem cells in multiple myeloma

(2018) Makoto Nakagawa et al.   CANCER SCIENCE

Emerging role of noncanonical polycomb repressive complexes in normal and malignant hematopoiesis

(2018) Yusuke Isshiki et al.   EXPERIMENTAL HEMATOLOGY

PRC2 loss induces chemoresistance by repressing apoptosis in T cell acute lymphoblastic leukemia

(2018) Ingrid M. Ariës et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer

(2018) Kathleen Moore et al.   NEW ENGLAND JOURNAL OF MEDICINE

Internal deletion of BCOR reveals a tumor suppressor function for BCOR in T lymphocyte malignancies

(2017) Tomoyuki Tanaka et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Dual inhibition of EZH1/2 breaks the quiescence of leukemia stem cells in acute myeloid leukemia

(2017) S Fujita et al.   LEUKEMIA

An allosteric PRC2 inhibitor targeting the H3K27me3 binding pocket of EED

(2017) Wei Qi et al.   Nature Chemical Biology

Recurrent SPI1 (PU.1) fusions in high-risk pediatric T cell acute lymphoblastic leukemia

(2017) Masafumi Seki et al.   NATURE GENETICS

EZH2 is a potential therapeutic target for H3K27M-mutant pediatric gliomas

(2017) Faizaan Mohammad et al.   NATURE MEDICINE

Genomic characterisation of Eμ-Myc mouse lymphomas identifies Bcor as a Myc co-operative tumour-suppressor gene

(2017) Marcus Lefebure et al.   Nature Communications

Loss of Ezh2 cooperates with Jak2V617F in the development of myelofibrosis in a mouse model of myeloproliferative neoplasm

(2016) Yue Yang et al.   BLOOD

EZH2 and BCL6 Cooperate to Assemble CBX8-BCOR Complex to Repress Bivalent Promoters, Mediate Germinal Center Formation and Lymphomagenesis

(2016) Wendy Béguelin et al.   CANCER CELL

Ezh2 regulates the Lin28/let-7 pathway to restrict activation of fetal gene signature in adult hematopoietic stem cells

(2016) Motohiko Oshima et al.   EXPERIMENTAL HEMATOLOGY

Role of TET enzymes in DNA methylation, development, and cancer

(2016) Kasper Dindler Rasmussen et al.   GENES & DEVELOPMENT

FrequentBCORaberrations in extranodal NK/T-Cell lymphoma, nasal type

(2016) Akito Dobashi et al.   GENES CHROMOSOMES & CANCER

Histone demethylase KDM2B regulates lineage commitment in normal and malignant hematopoiesis

(2016) Jaclyn Andricovich et al.   JOURNAL OF CLINICAL INVESTIGATION

Loss ofEzh2synergizes withJAK2-V617F in initiating myeloproliferative neoplasms and promoting myelofibrosis

(2016) Takafumi Shimizu et al.   JOURNAL OF EXPERIMENTAL MEDICINE

The loss of Ezh2 drives the pathogenesis of myelofibrosis and sensitizes tumor-initiating cells to bromodomain inhibition

(2016) Goro Sashida et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Impact of combinatorial dysfunctions of Tet2 and Ezh2 on the epigenome in the pathogenesis of myelodysplastic syndrome

(2016) N Hasegawa et al.   LEUKEMIA

BCOR regulates myeloid cell proliferation and differentiation

(2016) Q Cao et al.   LEUKEMIA

Loss of the histone methyltransferase EZH2 induces resistance to multiple drugs in acute myeloid leukemia

(2016) Stefanie Göllner et al.   NATURE MEDICINE

An oncogenic Ezh2 mutation induces tumors through global redistribution of histone 3 lysine 27 trimethylation

(2016) George P Souroullas et al.   NATURE MEDICINE

TP53 and Decitabine in Acute Myeloid Leukemia and Myelodysplastic Syndromes

(2016) John S. Welch et al.   NEW ENGLAND JOURNAL OF MEDICINE

Ezh2 Controls an Early Hematopoietic Program and Growth and Survival Signaling in Early T Cell Precursor Acute Lymphoblastic Leukemia

(2016) Etienne Danis et al.   Cell Reports

Non-canonical PRC1.1 Targets Active Genes Independent of H3K27me3 and Is Essential for Leukemogenesis

(2016) Vincent van den Boom et al.   Cell Reports

Polycomb repressive complex 2 component Suz12 is required for hematopoietic stem cell function and lymphopoiesis

(2015) S. C. W. Lee et al.   BLOOD

Fbxl10 overexpression in murine hematopoietic stem cells induces leukemia involving metabolic activation and upregulation of Nsg2

(2015) T. Ueda et al.   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

SRSF2 Mutations Contribute to Myelodysplasia by Mutant-Specific Effects on Exon Recognition

(2015) Eunhee Kim et al.   CANCER CELL

Genetic characterization of T-PLL reveals two major biologic subgroups andJAK3mutations as prognostic marker

(2015) Anna Stengel et al.   GENES CHROMOSOMES & CANCER

Mutations driving CLL and their evolution in progression and relapse

(2015) Dan A. Landau et al.   NATURE

Epigenetic silencing of TH1-type chemokines shapes tumour immunity and immunotherapy

(2015) Dongjun Peng et al.   NATURE

The epigenetic modifier EZH2 controls melanoma growth and metastasis through silencing of distinct tumour suppressors

(2015) Daniel Zingg et al.   Nature Communications

Genetic alterations of JAK/STAT cascade and histone modification in extranodal NK/T-cell lymphoma nasal type

(2015) Seungbok Lee et al.   Oncotarget

Integrated genomic sequencing reveals mutational landscape of T-cell prolymphocytic leukemia

(2014) M. J. Kiel et al.   BLOOD

Driver somatic mutations identify distinct disease entities within myeloid neoplasms with myelodysplasia

(2014) L. Malcovati 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

Acute myeloid leukemia ontogeny is defined by distinct somatic mutations

(2014) R. C. Lindsley et al.   BLOOD

BMI1 gene expression in myeloid leukemias and its impact on prognosis

(2014) Niveen S. Saudy et al.   BLOOD CELLS MOLECULES AND DISEASES

The number of prognostically detrimental mutations and prognosis in primary myelofibrosis: an international study of 797 patients

(2014) P Guglielmelli et al.   LEUKEMIA

PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4-based therapies

(2014) Thomas De Raedt et al.   NATURE

Synergistic Anti-Tumor Activity of EZH2 Inhibitors and Glucocorticoid Receptor Agonists in Models of Germinal Center Non-Hodgkin Lymphomas

(2014) Sarah K. Knutson et al.   PLoS One

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

(2014) Goro Sashida et al.   Nature Communications

An Orally Bioavailable Chemical Probe of the Lysine Methyltransferases EZH2 and EZH1

(2013) Kyle D. Konze et al.   ACS Chemical Biology

BCOR and BCORL1 mutations in myelodysplastic syndromes and related disorders

(2013) F. Damm et al.   BLOOD

EZH2 mutations are frequent and represent an early event in follicular lymphoma

(2013) C. Bodor et al.   BLOOD

Nonredundant and locus-specific gene repression functions of PRC1 paralog family members in human hematopoietic stem/progenitor cells

(2013) V. van den Boom et al.   BLOOD

Clinical and biological implications of driver mutations in myelodysplastic syndromes

(2013) E. Papaemmanuil et al.   BLOOD

EZH2 Is Required for Germinal Center Formation and Somatic EZH2 Mutations Promote Lymphoid Transformation

(2013) Wendy Béguelin et al.   CANCER CELL

Selective Inhibition of Tumor Oncogenes by Disruption of Super-Enhancers

(2013) Jakob Lovén et al.   CELL

Polycomb Repressive Complex 2 Regulates Normal Hematopoietic Stem Cell Function in a Developmental-Stage-Specific Manner

(2013) Huafeng Xie et al.   Cell Stem Cell

Germinal center dysregulation by histone methyltransferase EZH2 promotes lymphomagenesis

(2013) Marieta Caganova et al.   JOURNAL OF CLINICAL INVESTIGATION

Prognostic Score Including Gene Mutations in Chronic Myelomonocytic Leukemia

(2013) Raphaël Itzykson et al.   JOURNAL OF CLINICAL ONCOLOGY

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

Multiple mechanisms deregulate EZH2 and histone H3 lysine 27 epigenetic changes in myeloid malignancies

(2013) S N Khan et al.   LEUKEMIA

Landscape of genetic lesions in 944 patients with myelodysplastic syndromes

(2013) T Haferlach et al.   LEUKEMIA

The landscape of somatic mutations in Down syndrome–related myeloid disorders

(2013) Kenichi Yoshida et al.   NATURE GENETICS

Genomic and Epigenomic Landscapes of Adult De Novo Acute Myeloid Leukemia

(2013)   NEW ENGLAND JOURNAL OF MEDICINE

Polycomb group ring finger 1 cooperates with Runx1 in regulating differentiation and self-renewal of hematopoietic cells

(2012) K. Ross et al.   BLOOD

Ezh2 augments leukemogenicity by reinforcing differentiation blockage in acute myeloid leukemia

(2012) S. Tanaka et al.   BLOOD

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

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

Ezh1 Is Required for Hematopoietic Stem Cell Maintenance and Prevents Senescence-like Cell Cycle Arrest

(2012) Isabel Hidalgo et al.   Cell Stem Cell

A key role for EZH2 and associated genes in mouse and human adult T-cell acute leukemia

(2012) C. Simon et al.   GENES & DEVELOPMENT

Validation of a Prognostic Model and the Impact of Mutations in Patients With Lower-Risk Myelodysplastic Syndromes

(2012) Rafael Bejar et al.   JOURNAL OF CLINICAL ONCOLOGY

The genetic basis of early T-cell precursor acute lymphoblastic leukaemia

(2012) Jinghui Zhang et al.   NATURE

Genetic inactivation of the polycomb repressive complex 2 in T cell acute lymphoblastic leukemia

(2012) Panagiotis Ntziachristos 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

Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing

(2012) J. G. Lohr et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Somatic mutations in the transcriptional corepressor gene BCORL1 in adult acute myelogenous leukemia

(2011) M. Li et al.   BLOOD

Whole-exome sequencing identifies somatic mutations of BCOR in acute myeloid leukemia with normal karyotype

(2011) V. Grossmann et al.   BLOOD

Dependency on the polycomb gene Ezh2 distinguishes fetal from adult hematopoietic stem cells

(2011) M. Mochizuki-Kashio et al.   BLOOD

Inactivation of polycomb repressive complex 2 components in myeloproliferative and myelodysplastic/myeloproliferative neoplasms

(2011) J. Score et al.   BLOOD

Forced expression of the histone demethylase Fbxl10 maintains self-renewing hematopoietic stem cells

(2011) Takaaki Konuma et al.   EXPERIMENTAL HEMATOLOGY

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

(2011) M. Pratcorona et al.   HAEMATOLOGICA

Prognostic Significance of ASXL1 Mutations in Patients With Myelodysplastic Syndromes

(2011) Felicitas Thol et al.   JOURNAL OF CLINICAL ONCOLOGY

Molecular profiling of chronic myelomonocytic leukemia reveals diverse mutations in >80% of patients with TET2 and EZH2 being of high prognostic relevance

(2011) V Grossmann et al.   LEUKEMIA

Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma

(2011) Ryan D. Morin et al.   NATURE

Clinical Effect of Point Mutations in Myelodysplastic Syndromes

(2011) Rafael Bejar et al.   NEW ENGLAND JOURNAL OF MEDICINE

Mutations and deletions of the SUZ12 polycomb gene in myeloproliferative neoplasms

(2011) M Brecqueville et al.   Blood Cancer Journal

Poised Lineage Specification in Multipotential Hematopoietic Stem and Progenitor Cells by the Polycomb Protein Bmi1

(2010) Hideyuki Oguro et al.   Cell Stem Cell

Histone H2A deubiquitinase activity of the Polycomb repressive complex PR-DUB

(2010) Johanna C. Scheuermann et al.   NATURE

Somatic mutations of the histone methyltransferase gene EZH2 in myelodysplastic syndromes

(2010) Gorica Nikoloski et al.   NATURE GENETICS

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

MDS and secondary AML display unique patterns and abundance of aberrant DNA methylation

(2009) M. E. Figueroa et al.   BLOOD

Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study

(2009) Pierre Fenaux et al.   LANCET ONCOLOGY

Identification of miR-145 and miR-146a as mediators of the 5q– syndrome phenotype

(2009) Daniel T Starczynowski et al.   NATURE MEDICINE