Rewiring the Epigenetic Networks in MLL-Rearranged Leukemias: Epigenetic Dysregulation and Pharmacological Interventions

The DOT1L inhibitor pinometostat reduces H3K79 methylation and has modest clinical activity in adult acute leukemia

(2018) Eytan M. Stein et al.   BLOOD

LSD1 inhibition exerts its antileukemic effect by recommissioning PU.1- and C/EBPα-dependent enhancers in AML

(2018) Monica Cusan et al.   BLOOD

ORY-1001, a Potent and Selective Covalent KDM1A Inhibitor, for the Treatment of Acute Leukemia

(2018) Tamara Maes et al.   CANCER CELL

Small molecules as tools to study the chemical epigenetics of lysine acetylation

(2018) Matthias Schiedel et al.   CURRENT OPINION IN CHEMICAL BIOLOGY

Complexity of Blocking Bivalent Protein–Protein Interactions: Development of a Highly Potent Inhibitor of the Menin–Mixed-Lineage Leukemia Interaction

(2018) Dmitry Borkin et al.   JOURNAL OF MEDICINAL CHEMISTRY

The dTAG system for immediate and target-specific protein degradation

(2018) Behnam Nabet et al.   Nature Chemical Biology

Regulation of MLL/COMPASS stability through its proteolytic cleavage by taspase1 as a possible approach for clinical therapy of leukemia

(2018) Zibo Zhao et al.   GENES & DEVELOPMENT

Structure-guided development of YEATS domain inhibitors by targeting π-π-π stacking

(2018) Xin Li et al.   Nature Chemical Biology

Discovery of a Selective Inhibitor for the YEATS Domains of ENL/AF9

(2018) Thomas Christott et al.   SLAS Discovery

The MLL recombinome of acute leukemias in 2017

(2017) C Meyer et al.   LEUKEMIA

Discovery of a selective catalytic p300/CBP inhibitor that targets lineage-specific tumours

(2017) Loren M. Lasko et al.   NATURE

Transcription control by the ENL YEATS domain in acute leukaemia

(2017) Michael A. Erb et al.   NATURE

ENL links histone acetylation to oncogenic gene expression in acute myeloid leukaemia

(2017) Liling Wan et al.   NATURE

Computational correction of copy number effect improves specificity of CRISPR–Cas9 essentiality screens in cancer cells

(2017) Robin M Meyers et al.   NATURE GENETICS

Functions of bromodomain-containing proteins and their roles in homeostasis and cancer

(2017) Takao Fujisawa et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Mixed-Lineage Leukemia Fusions and Chromatin in Leukemia

(2017) Andrei V. Krivtsov et al.   Cold Spring Harbor Perspectives in Medicine

Targeting Cancer Cells with BET Bromodomain Inhibitors

(2017) Yali Xu et al.   Cold Spring Harbor Perspectives in Medicine

The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia

(2016) D. A. Arber et al.   BLOOD

Instructive Role of MLL-Fusion Proteins Revealed by a Model of t(4;11) Pro-B Acute Lymphoblastic Leukemia

(2016) Shan Lin et al.   CANCER CELL

SnapShot: Transcription Elongation

(2016) Christine E. Cucinotta et al.   CELL

Deregulation of the HOXA9/MEIS1 axis in acute leukemia

(2016) Cailin T. Collins et al.   CURRENT OPINION IN HEMATOLOGY

Inhibitors of LSD1 as a potential therapy for acute myeloid leukemia

(2016) Amanda Przespolewski et al.   EXPERT OPINION ON INVESTIGATIONAL DRUGS

Structure-Based Design of an in Vivo Active Selective BRD9 Inhibitor

(2016) Laetitia J. Martin et al.   JOURNAL OF MEDICINAL CHEMISTRY

Complementary activities of DOT1L and Menin inhibitors in MLL-rearranged leukemia

(2016) C Dafflon et al.   LEUKEMIA

Structural basis for activity regulation of MLL family methyltransferases

(2016) Yanjing Li et al.   NATURE

Sensitivity and engineered resistance of myeloid leukemia cells to BRD9 inhibition

(2016) Anja F Hohmann et al.   Nature Chemical Biology

Functional interdependence of BRD4 and DOT1L in MLL leukemia

(2016) Omer Gilan et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Genomic Classification and Prognosis in Acute Myeloid Leukemia

(2016) Elli Papaemmanuil et al.   NEW ENGLAND JOURNAL OF MEDICINE

The molecular mechanics of mixed lineage leukemia

(2016) R K Slany   ONCOGENE

LSD1: biologic roles and therapeutic targeting

(2016) Alba Maiques-Diaz et al.   Epigenomics

ASH1L Links Histone H3 Lysine 36 Dimethylation to MLL Leukemia

(2016) L. Zhu et al.   Cancer Discovery

Functional interdependence of BRD4 and DOT1L in MLL leukemia

(2016) Omer Gilan et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

MLL1 and MLL1 fusion proteins have distinct functions in regulating leukemic transcription program

(2016) Jing Xu et al.   Cell Discovery

MLL leukemia induction by genome editing of human CD34+ hematopoietic cells

(2015) C. Buechele et al.   BLOOD

Pharmacologic Inhibition of the Menin-MLL Interaction Blocks Progression of MLL Leukemia In Vivo

(2015) Dmitry Borkin et al.   CANCER CELL

Generation of a Selective Small Molecule Inhibitor of the CBP/p300 Bromodomain for Leukemia Therapy

(2015) S. Picaud et al.   CANCER RESEARCH

The interplay of histone modifications - writers that read

(2015) T. Zhang et al.   EMBO REPORTS

Targeting DOT1L and HOX gene expression in MLL-rearranged leukemia and beyond

(2015) Chun-Wei Chen et al.   EXPERIMENTAL HEMATOLOGY

Drugging Chromatin in Cancer: Recent Advances and Novel Approaches

(2015) Sheng F. Cai et al.   MOLECULAR CELL

BET Bromodomain Inhibition Suppresses the Function of Hematopoietic Transcription Factors in Acute Myeloid Leukemia

(2015) Jae-Seok Roe et al.   MOLECULAR CELL

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

Genomics in acute lymphoblastic leukaemia: insights and treatment implications

(2015) Kathryn G. Roberts et al.   Nature Reviews Clinical Oncology

High-throughput functional genomics using CRISPR–Cas9

(2015) Ophir Shalem et al.   NATURE REVIEWS GENETICS

Acute Myeloid Leukemia

(2015) Hartmut Döhner et al.   NEW ENGLAND JOURNAL OF MEDICINE

Phthalimide conjugation as a strategy for in vivo target protein degradation

(2015) G. E. Winter et al.   SCIENCE

Small Molecule Inhibitors of Bromodomain–Acetyl-lysine Interactions

(2014) Michael Brand et al.   ACS Chemical Biology

A Series of Potent CREBBP Bromodomain Ligands Reveals an Induced-Fit Pocket Stabilized by a Cation-π Interaction

(2014) Timothy P. C. Rooney et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Nonclinical pharmacokinetics and metabolism of EPZ-5676, a novel DOT1L histone methyltransferase inhibitor

(2014) Aravind Basavapathruni et al.   BIOPHARMACEUTICS & DRUG DISPOSITION

Lysine-specific demethylase 1 (LSD1) in hematopoietic and lymphoid neoplasms

(2014) D. Niebel et al.   BLOOD

AF9 YEATS Domain Links Histone Acetylation to DOT1L-Mediated H3K79 Methylation

(2014) Yuanyuan Li et al.   CELL

SIRT1 Activation by a c-MYC Oncogenic Network Promotes the Maintenance and Drug Resistance of Human FLT3-ITD Acute Myeloid Leukemia Stem Cells

(2014) Ling Li et al.   Cell Stem Cell

Two decades of leukemia oncoprotein epistasis: the MLL1 paradigm for epigenetic deregulation in leukemia

(2014) Bin E. Li et al.   EXPERIMENTAL HEMATOLOGY

Discovery and Optimization of Small-Molecule Ligands for the CBP/p300 Bromodomains

(2014) Duncan A. Hay et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

The Mechanisms behind the Therapeutic Activity of BET Bromodomain Inhibition

(2014) Junwei Shi et al.   MOLECULAR CELL

Targeting bromodomains: epigenetic readers of lysine acetylation

(2014) Panagis Filippakopoulos et al.   NATURE REVIEWS DRUG DISCOVERY

Erasers of Histone Acetylation: The Histone Deacetylase Enzymes

(2014) E. Seto et al.   Cold Spring Harbor Perspectives in Biology

The SIRT1 Activator SRT1720 Extends Lifespan and Improves Health of Mice Fed a Standard Diet

(2014) Sarah J. Mitchell et al.   Cell Reports

The Histone Methyltransferase Activity of MLL1 Is Dispensable for Hematopoiesis and Leukemogenesis

(2014) Bibhu P. Mishra et al.   Cell Reports

The histone LSD1 demethylase in stemness and cancer transcription programs

(2013) Stefano Amente et al.   Biochimica et Biophysica Acta-Gene Regulatory Mechanisms

Diverse functions of PHD fingers of the MLL/KMT2 subfamily

(2013) Muzaffar Ali et al.   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH

Distinct pathways regulated by menin and by MLL1 in hematopoietic stem cells and developing B cells

(2013) B. E. Li et al.   BLOOD

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

Selective Inhibition of Tumor Oncogenes by Disruption of Super-Enhancers

(2013) Jakob Lovén et al.   CELL

Super-Enhancers in the Control of Cell Identity and Disease

(2013) Denes Hnisz et al.   CELL

Role of SWI/SNF in acute leukemia maintenance and enhancer-mediated Myc regulation

(2013) J. Shi et al.   GENES & DEVELOPMENT

Targeting Recruitment of Disruptor of Telomeric Silencing 1-like (DOT1L)

(2013) Chenxi Shen et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

A Medicinal Chemistry Perspective for Targeting Histone H3 Lysine-79 Methyltransferase DOT1L

(2013) Justin L. Anglin et al.   JOURNAL OF MEDICINAL CHEMISTRY

Acute lymphoblastic leukaemia

(2013) Hiroto Inaba et al.   LANCET

Structural basis for high-affinity binding of LEDGF PWWP to mononucleosomes

(2013) Jocelyn O. Eidahl et al.   NUCLEIC ACIDS RESEARCH

Breaking the LSD1/KDM1A Addiction: Therapeutic Targeting of the Epigenetic Modifier in AML

(2012) Alyson A. Lokken 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

MYC on the Path to Cancer

(2012) Chi V. Dang   CELL

Histone Recognition and Large-Scale Structural Analysis of the Human Bromodomain Family

(2012) Panagis Filippakopoulos et al.   CELL

Abrogation of MLL–AF10 and CALM–AF10-mediated transformation through genetic inactivation or pharmacological inhibition of the H3K79 methyltransferase Dot1l

(2012) L Chen et al.   LEUKEMIA

Cell of origin determines clinically relevant subtypes of MLL-rearranged AML

(2012) A V Krivtsov et al.   LEUKEMIA

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

Epigenetic protein families: a new frontier for drug discovery

(2012) Cheryl H. Arrowsmith et al.   NATURE REVIEWS DRUG DISCOVERY

The super elongation complex (SEC) family in transcriptional control

(2012) Zhuojuan Luo et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Perceiving the epigenetic landscape through histone readers

(2012) Catherine A Musselman et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

BRD4 is an atypical kinase that phosphorylates Serine2 of the RNA Polymerase II carboxy-terminal domain

(2012) B. N. Devaiah et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Psip1/Ledgf p52 Binds Methylated Histone H3K36 and Splicing Factors and Contributes to the Regulation of Alternative Splicing

(2012) Madapura M. Pradeepa et al.   PLoS Genetics

The Pathogenesis of Mixed-Lineage Leukemia

(2011) Andrew G. Muntean et al.   Annual Review of Pathology-Mechanisms of Disease

MLL fusion proteins preferentially regulate a subset of wild-type MLL target genes in the leukemic genome

(2011) Q.-f. Wang et al.   BLOOD

Requirement for Dot1l in murine postnatal hematopoiesis and leukemogenesis by MLL translocation

(2011) S. Y. Jo et al.   BLOOD

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

(2011) A. T. Nguyen 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

Dynamic chromatin states in human ES cells reveal potential regulatory sequences and genes involved in pluripotency

(2011) R David Hawkins et al.   CELL RESEARCH

Regulation of chromatin by histone modifications

(2011) Andrew J Bannister et al.   CELL RESEARCH

A Small Molecule Binding to the Coactivator CREB-Binding Protein Blocks Apoptosis in Cardiomyocytes

(2011) Jagat C. Borah et al.   CHEMISTRY & BIOLOGY

Pluripotency-related, Valproic Acid (VPA)-induced Genome-wide Histone H3 Lysine 9 (H3K9) Acetylation Patterns in Embryonic Stem Cells

(2011) Hadas Hezroni et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Activated K-Ras protein accelerates human MLL/AF4-induced leukemo-lymphomogenicity in a transgenic mouse model

(2011) H Tamai et al.   LEUKEMIA

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

Function of leukemogenic mixed lineage leukemia 1 (MLL) fusion proteins through distinct partner protein complexes

(2011) D. Biswas et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Targeting Epigenetic Programs in MLL-Rearranged Leukemias

(2011) K. M. Bernt et al.   Hematology-American Society of Hematology Education Program

A Higher-Order Complex Containing AF4 and ENL Family Proteins with P-TEFb Facilitates Oncogenic and Physiologic MLL-Dependent Transcription

(2010) Akihiko Yokoyama et al.   CANCER CELL

The PAF Complex Synergizes with MLL Fusion Proteins at HOX Loci to Promote Leukemogenesis

(2010) Andrew G. Muntean et al.   CANCER CELL

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

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

Overexpression of LSD1 contributes to human carcinogenesis through chromatin regulation in various cancers

(2010) Shinya Hayami et al.   INTERNATIONAL JOURNAL OF CANCER

Binding of the MLL PHD3 Finger to Histone H3K4me3 Is Required for MLL-Dependent Gene Transcription

(2010) Pei-Yun Chang et al.   JOURNAL OF MOLECULAR BIOLOGY

Genetic aberrations in paediatric acute leukaemias and implications for management of patients

(2010) Tomasz Szczepański et al.   LANCET ONCOLOGY

Suppression of inflammation by a synthetic histone mimic

(2010) Edwige Nicodeme et al.   NATURE

Selective inhibition of BET bromodomains

(2010) Panagis Filippakopoulos et al.   NATURE

Crosstalk between leukemia-associated proteins MOZ and MLL regulates HOX gene expression in human cord blood CD34+ cells

(2010) J Paggetti et al.   ONCOGENE

Histone H3K27ac separates active from poised enhancers and predicts developmental state

(2010) M. P. Creyghton et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Characterization of the DOT1L Network: Implications of Diverse Roles for DOT1L

(2010) Geunyeong Park et al.   PROTEIN JOURNAL

The structure of the FYR domain of transforming growth factor beta regulator 1

(2010) María M. García-Alai et al.   PROTEIN SCIENCE

Novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia: results of an international retrospective study

(2009) B. V. Balgobind et al.   BLOOD

Lysine-specific demethylase 1 (LSD1) is highly expressed in ER-negative breast cancers and a biomarker predicting aggressive biology

(2009) Soyoung Lim et al.   CARCINOGENESIS

The molecular biology of mixed lineage leukemia

(2009) R. K. Slany   HAEMATOLOGICA

On the Mechanism of Multiple Lysine Methylation by the Human Mixed Lineage Leukemia Protein-1 (MLL1) Core Complex

(2009) Anamika Patel et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Genome-wide reduction in H3K9 acetylation during human embryonic stem cell differentiation

(2009) Jana Krejčí et al.   JOURNAL OF CELLULAR PHYSIOLOGY

Global Analysis of H3K4 Methylation Defines MLL Family Member Targets and Points to a Role for MLL1-Mediated H3K4 Methylation in the Regulation of Transcriptional Initiation by RNA Polymerase II

(2009) P. Wang et al.   MOLECULAR AND CELLULAR BIOLOGY

Brd4 Marks Select Genes on Mitotic Chromatin and Directs Postmitotic Transcription

(2009) Anup Dey et al.   MOLECULAR BIOLOGY OF THE CELL

Genomic analysis reveals few genetic alterations in pediatric acute myeloid leukemia

(2009) I. Radtke et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Menin Critically Links MLL Proteins with LEDGF on Cancer-Associated Target Genes

(2008) Akihiko Yokoyama et al.   CANCER CELL

H3K79 Methylation Profiles Define Murine and Human MLL-AF4 Leukemias

(2008) Andrei V. Krivtsov et al.   CANCER CELL

Structure of WDR5 Bound to Mixed Lineage Leukemia Protein-1 Peptide

(2008) Anamika Patel et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Alterations of the CxxC domain preclude oncogenic activation of mixed-lineage leukemia 2

(2008) C Bach et al.   ONCOGENE

Insights from clinical studies into the role of the MLL gene in infant and childhood leukemia

(2007) Tanzina Chowdhury et al.   BLOOD CELLS MOLECULES AND DISEASES