MLL-Rearranged Leukemias—An Update on Science and Clinical Approaches

Venetoclax responses of pediatric ALL xenografts reveal sensitivity of MLL-rearranged leukemia

(2016) S. L. Khaw et al.   BLOOD

Acquisition of a CD19-negative myeloid phenotype allows immune escape of MLL-rearranged B-ALL from CD19 CAR-T-cell therapy

(2016) R. Gardner et al.   BLOOD

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

(2016) D. A. Arber et al.   BLOOD

Long-term follow-up of therapy-related myelodysplasia and AML patients treated with allogeneic hematopoietic cell transplantation

(2016) J Finke et al.   BONE MARROW TRANSPLANTATION

A Phase I Study of Quizartinib Combined with Chemotherapy in Relapsed Childhood Leukemia: A Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) Study

(2016) Todd M. Cooper et al.   CLINICAL CANCER RESEARCH

Discovery of Novel Inhibitors Targeting the Menin-Mixed Lineage Leukemia Interface Using Pharmacophore- and Docking-Based Virtual Screening

(2016) Yuan Xu et al.   Journal of Chemical Information and Modeling

Pharmacological inhibition of LSD1 for the treatment of MLL-rearranged leukemia

(2016) Zizhen Feng et al.   Journal of Hematology & Oncology

Property Focused Structure-Based Optimization of Small Molecule Inhibitors of the Protein–Protein Interaction between Menin and Mixed Lineage Leukemia (MLL)

(2016) Dmitry Borkin et al.   JOURNAL OF MEDICINAL CHEMISTRY

Identification of phenoxyacetamide derivatives as novel DOT1L inhibitors via docking screening and molecular dynamics simulation

(2016) Minghao Luo et al.   JOURNAL OF MOLECULAR GRAPHICS & MODELLING

Systematic chemical and molecular profiling of MLL-rearranged infant acute lymphoblastic leukemia reveals efficacy of romidepsin

(2016) M N Cruickshank et al.   LEUKEMIA

Molecular Coupling of Histone Crotonylation and Active Transcription by AF9 YEATS Domain

(2016) Yuanyuan Li et al.   MOLECULAR CELL

PAX5 promotes pre-B cell proliferation by regulating the expression of pre-B cell receptor and its downstream signaling

(2016) Kai Xue et al.   MOLECULAR IMMUNOLOGY

Structural basis for activity regulation of MLL family methyltransferases

(2016) Yanjing Li et al.   NATURE

Functional interdependence of BRD4 and DOT1L in MLL leukemia

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

Targeting BCL2 with Venetoclax in Relapsed Chronic Lymphocytic Leukemia

(2016) Andrew W. Roberts et al.   NEW ENGLAND JOURNAL OF MEDICINE

Lineage Switch in MLL-Rearranged Infant Leukemia Following CD19-Directed Therapy

(2016) Ahmad Rayes et al.   PEDIATRIC BLOOD & CANCER

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

MEK inhibition is a promising therapeutic strategy for MLL-rearranged infant acute lymphoblastic leukemia patients carrying RAS mutations

(2016) Mark Kerstjens et al.   Oncotarget

Systematic Classification of Mixed-Lineage Leukemia Fusion Partners Predicts Additional Cancer Pathways

(2016) Rolf Marschalek   Annals of Laboratory Medicine

Leukemogenic MLL-ENL Fusions Induce Alternative Chromatin States to Drive a Functionally Dichotomous Group of Target Genes

(2016) Maria-Paz Garcia-Cuellar et al.   Cell Reports

Targeting epigenetic pathways in acute myeloid leukemia and myelodysplastic syndrome: a systematic review of hypomethylating agents trials

(2016) Seongseok Yun et al.   Clinical Epigenetics

Maintenance of leukemic cell identity by the activity of the Polycomb complex PRC1 in mice

(2016) A. Rossi et al.   Science Advances

Functional-genetic dissection of HDAC dependencies in mouse lymphoid and myeloid malignancies

(2015) G. M. Matthews et al.   BLOOD

Subclonality and prenatal origin ofRASmutations inKMT2A (MLL)-rearranged infant acute lymphoblastic leukaemia

(2015) Mariana Emerenciano et al.   BRITISH JOURNAL OF HAEMATOLOGY

New insights into the pathophysiology and therapy of adult acute lymphoblastic leukemia

(2015) Elias Jabbour et al.   CANCER

The CDK9 Inhibitor Dinaciclib Exerts Potent Apoptotic and Antitumor Effects in Preclinical Models of MLL-Rearranged Acute Myeloid Leukemia

(2015) A. Baker et al.   CANCER RESEARCH

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

(2015) S. Picaud et al.   CANCER RESEARCH

Selective Inhibition of HDAC1 and HDAC2 as a Potential Therapeutic Option for B-ALL

(2015) M. C. Stubbs et al.   CLINICAL CANCER RESEARCH

The potential of clofarabine in MLL -rearranged infant acute lymphoblastic leukaemia

(2015) Dominique J.P.M. Stumpel et al.   EUROPEAN JOURNAL OF CANCER

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

Collaborative Efforts Driving Progress in Pediatric Acute Myeloid Leukemia

(2015) C. Michel Zwaan et al.   JOURNAL OF CLINICAL ONCOLOGY

Menin-MLL inhibitors block oncogenic transformation by MLL-fusion proteins in a fusion partner-independent manner

(2015) S He et al.   LEUKEMIA

The PZP Domain of AF10 Senses Unmodified H3K27 to Regulate DOT1L-Mediated Methylation of H3K79

(2015) Shoudeng Chen et al.   MOLECULAR CELL

The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias

(2015) Anna K Andersson et al.   NATURE GENETICS

The transcriptomic landscape and directed chemical interrogation of MLL-rearranged acute myeloid leukemias

(2015) Vincent-Philippe Lavallée et al.   NATURE GENETICS

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

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

Acute Lymphoblastic Leukemia in Children

(2015) Stephen P. Hunger et al.   NEW ENGLAND JOURNAL OF MEDICINE

AF4 uses the SL1 components of RNAP1 machinery to initiate MLL fusion- and AEP-dependent transcription

(2015) Hiroshi Okuda et al.   Nature Communications

MLL-Rearranged Acute Lymphoblastic Leukemias Activate BCL-2 through H3K79 Methylation and Are Sensitive to the BCL-2-Specific Antagonist ABT-199

(2015) Juliana M. Benito et al.   Cell Reports

MLL-AF6 fusion oncogene sequesters AF6 into the nucleus to trigger RAS activation in myeloid leukemia

(2014) E. Manara et al.   BLOOD

Requirement for CDK6 in MLL-rearranged acute myeloid leukemia

(2014) T. Placke 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

Proteasome Inhibitors Evoke Latent Tumor Suppression Programs in Pro-B MLL Leukemias through MLL-AF4

(2014) Han Liu et al.   CANCER CELL

AF10 Regulates Progressive H3K79 Methylation and HOX Gene Expression in Diverse AML Subtypes

(2014) Aniruddha J. Deshpande et al.   CANCER CELL

Inhibition of histone methyltransferase EZH2 depletes leukemia stem cell of mixed lineage leukemia fusion leukemia through upregulation of p16

(2014) Koki Ueda et al.   CANCER SCIENCE

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

(2014) Yuanyuan Li et al.   CELL

MLL fusion-driven activation ofCDK6potentiates proliferation inMLL-rearranged infant ALL

(2014) Marieke Van der Linden et al.   CELL CYCLE

FISH analysis ofMLLgene rearrangements: detection of the concurrent loss or gain of the 3′ signal and its prognostic significance

(2014) J.-H. Lim et al.   International Journal of Laboratory Hematology

Loss of TBL1XR1 Disrupts Glucocorticoid Receptor Recruitment to Chromatin and Results in Glucocorticoid Resistance in a B-Lymphoblastic Leukemia Model

(2014) Courtney L. Jones et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Positive feedback between NF-κB and TNF-α promotes leukemia-initiating cell capacity

(2014) Yuki Kagoya et al.   JOURNAL OF CLINICAL INVESTIGATION

Intensified chemotherapy without SCT in infant ALL: Results from COG P9407 (Cohort 3)

(2014) ZoAnn E. Dreyer et al.   PEDIATRIC BLOOD & CANCER

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

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

Inhibition of class I HDACs abrogates the dominant effect of MLL-AF4 by activation of wild-type MLL

(2014) K Ahmad et al.   Oncogenesis

The Biology and Targeting of FLT3 in Pediatric Leukemia

(2014) Colleen E. Annesley et al.   Frontiers in Oncology

Potent inhibition of DOT1L as treatment of MLL-fusion leukemia

(2013) S. R. Daigle et al.   BLOOD

Potent obatoclax cytotoxicity and activation of triple death mode killing across infant acute lymphoblastic leukemia

(2013) K. A. Urtishak et al.   BLOOD

The distribution ofMLLbreakpoints correlates with outcome in infant acute leukaemia

(2013) Mariana Emerenciano et al.   BRITISH JOURNAL OF HAEMATOLOGY

Epigenetic Roles of MLL Oncoproteins Are Dependent on NF-κB

(2013) Hsu-Ping Kuo et al.   CANCER CELL

Clofarabine, a novel adenosine analogue, reactivates DNA methylation-silenced tumour suppressor genes and inhibits cell growth in breast cancer cells

(2013) Katarzyna Lubecka-Pietruszewska et al.   EUROPEAN JOURNAL OF PHARMACOLOGY

The clinical characteristics, therapy and outcome of 85 adults with acute lymphoblastic leukemia and t(4;11)(q21;q23)/MLL-AFF1 prospectively treated in the UKALLXII/ECOG2993 trial

(2013) D. I. Marks et al.   HAEMATOLOGICA

Frequencies and prognostic impact of RAS mutations in MLL-rearranged acute lymphoblastic leukemia in infants

(2013) E. M. C. Driessen et al.   HAEMATOLOGICA

Differential mRNA Expression Levels of Human Histone-Modifying Enzymes in Normal Karyotype B Cell Pediatric Acute Lymphoblastic Leukemia

(2013) Yan-Fang Tao et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Excess congenital non-synonymous variation in leukemia-associated genes in MLL− infant leukemia: a Children’s Oncology Group report

(2013) M C Valentine et al.   LEUKEMIA

Insights in dynamic kinome reprogramming as a consequence of MEK inhibition in MLL-rearranged AML

(2013) K R Kampen et al.   LEUKEMIA

The MLL recombinome of acute leukemias in 2013

(2013) C Meyer et al.   LEUKEMIA

The expression of histone deacetylase 4 is associated with prednisone poor-response in childhood acute lymphoblastic leukemia

(2013) Bernd Gruhn et al.   LEUKEMIA RESEARCH

Quizartinib (AC220) is a potent second generation class III tyrosine kinase inhibitor that displays a distinct inhibition profile against mutant-FLT3, -PDGFRA and -KIT isoforms

(2013) Kerstin Maria Kampa-Schittenhelm et al.   Molecular Cancer

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

(2013) Woojin Kim et al.   Nature Chemical Biology

ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets

(2013) Andrew J Souers et al.   NATURE MEDICINE

Histone H2B ubiquitin ligase RNF20 is required for MLL-rearranged leukemia

(2013) E. Wang et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

RUNX1 Is a Key Target in t(4;11) Leukemias that Contributes to Gene Activation through an AF4-MLL Complex Interaction

(2013) Adam C. Wilkinson et al.   Cell Reports

MLL-ENL Inhibits Polycomb Repressive Complex 1 to Achieve Efficient Transformation of Hematopoietic Cells

(2013) Emanuel Maethner et al.   Cell Reports

EVI1 is critical for the pathogenesis of a subset of MLL-AF9-rearranged AMLs

(2012) E. M. J. Bindels et al.   BLOOD

Epigenetic reprogramming reverses the relapse-specific gene expression signature and restores chemosensitivity in childhood B-lymphoblastic leukemia

(2012) T. Bhatla et al.   BLOOD

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

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

Proteasome Inhibitors: An Expanding Army Attacking a Unique Target

(2012) Alexei F. Kisselev et al.   CHEMISTRY & BIOLOGY

Prognostic significance of FLT3 mutational status and expression levels in MLL-AF4+ and MLL-germline acute lymphoblastic leukemia

(2012) M C Chillón et al.   LEUKEMIA

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

(2012) A V Krivtsov et al.   LEUKEMIA

Secondary mutations in t(4;11) leukemia patients

(2012) C Prelle et al.   LEUKEMIA

Menin-MLL inhibitors reverse oncogenic activity of MLL fusion proteins in leukemia

(2012) Jolanta Grembecka et al.   Nature Chemical Biology

The Polycomb complex PRC2 supports aberrant self-renewal in a mouse model of MLL-AF9;NrasG12D acute myeloid leukemia

(2012) J Shi et al.   ONCOGENE

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

The Pathogenesis of Mixed-Lineage Leukemia

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

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

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

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

CBX8, a Polycomb Group Protein, Is Essential for MLL-AF9-Induced Leukemogenesis

(2011) Jiaying Tan et al.   CANCER CELL

Functional Crosstalk between Bmi1 and MLL/Hoxa9 Axis in Establishment of Normal Hematopoietic and Leukemic Stem Cells

(2011) Lan-Lan Smith et al.   Cell Stem Cell

Proteolytically cleaved MLL subunits are susceptible to distinct degradation pathways

(2011) A. Yokoyama et al.   JOURNAL OF CELL SCIENCE

Connectivity mapping identifies HDAC inhibitors for the treatment of t(4;11)-positive infant acute lymphoblastic leukemia

(2011) D J P M Stumpel et al.   LEUKEMIA

Bmi1 is essential for leukemic reprogramming of myeloid progenitor cells

(2011) J Yuan 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

Trithorax group proteins: switching genes on and keeping them active

(2011) Bernd Schuettengruber et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

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

Human Polymerase-Associated Factor complex (PAFc) connects the Super Elongation Complex (SEC) to RNA polymerase II on chromatin

(2011) N. He et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Acute Myeloid Leukemia With t(9;11)(p21–22;q23)

(2010) Pranil Chandra et al.   AMERICAN JOURNAL OF CLINICAL PATHOLOGY

MLL-aberrant leukemia: complete cytogenetic remission following treatment with a histone deacetylase inhibitor (HDACi)

(2010) Kate L. Burbury et al.   ANNALS OF HEMATOLOGY

Improved outcome with hematopoietic stem cell transplantation in a poor prognostic subgroup of infants with mixed-lineage-leukemia (MLL)-rearranged acute lymphoblastic leukemia: results from the Interfant-99 Study

(2010) G. Mann et al.   BLOOD

Promoter hypermethylation in MLL-r infant acute lymphoblastic leukemia: biology and therapeutic targeting

(2010) E. Schafer et al.   BLOOD

research paper: Differential expression of HDAC3, HDAC7 and HDAC9 is associated with prognosis and survival in childhood acute lymphoblastic leukaemia

(2010) Daniel Antunes Moreno et al.   BRITISH JOURNAL OF HAEMATOLOGY

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

MLL-AF9-Induced Leukemogenesis Requires Coexpression of the Wild-Type Mll Allele

(2010) Austin T. Thiel 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

Linking H3K79 trimethylation to Wnt signaling through a novel Dot1-containing complex (DotCom)

(2010) M. Mohan et al.   GENES & DEVELOPMENT

Histone deacetylases 1 and 2 act in concert to promote the G1-to-S progression

(2010) T. Yamaguchi et al.   GENES & DEVELOPMENT

Analysis of the Role of Hematopoietic Stem-Cell Transplantation in Infants With Acute Lymphoblastic Leukemia in First Remission andMLLGene Rearrangements: A Report From the Children's Oncology Group

(2010) ZoAnn E. Dreyer et al.   JOURNAL OF CLINICAL ONCOLOGY

Multiple Interactions Recruit MLL1 and MLL1 Fusion Proteins to the HOXA9 Locus in Leukemogenesis

(2010) Thomas A. Milne et al.   MOLECULAR CELL

AFF4, a Component of the ELL/P-TEFb Elongation Complex and a Shared Subunit of MLL Chimeras, Can Link Transcription Elongation to Leukemia

(2010) Chengqi Lin et al.   MOLECULAR CELL

Specific promoter methylation identifies different subgroups of MLL-rearranged infant acute lymphoblastic leukemia, influences clinical outcome, and provides therapeutic options

(2009) D. J. P. M. Stumpel et al.   BLOOD

Outcome of congenital acute lymphoblastic leukemia treated on the Interfant-99 protocol

(2009) M. H. van der Linden et al.   BLOOD

Menin regulates the function of hematopoietic stem cells and lymphoid progenitors

(2009) I. Maillard et al.   BLOOD

AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML)

(2009) P. P. Zarrinkar et al.   BLOOD

Allogeneic transplantation for therapy-related myelodysplastic syndrome and acute myeloid leukemia

(2009) M. R. Litzow et al.   BLOOD

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

(2009) B. V. Balgobind et al.   BLOOD

The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes

(2009) J. W. Vardiman et al.   BLOOD

Consistent Deregulation of Gene Expression between Human and Murine MLL Rearrangement Leukemias

(2009) Z. Li et al.   CANCER RESEARCH

Prognostic significance of minimal residual disease in infants with acute lymphoblastic leukemia treated within the Interfant-99 protocol

(2009) V H J Van der Velden et al.   LEUKEMIA

Outcome of recurrent or refractory acute lymphoblastic leukemia in infants withMLLgene rearrangements: A report from the Japan infant leukemia study group

(2009) Daisuke Tomizawa et al.   PEDIATRIC BLOOD & CANCER

Misguided Transcriptional Elongation Causes Mixed Lineage Leukemia

(2009) Dorothee Mueller et al.   PLOS BIOLOGY

HOXA9 is required for survival in human MLL-rearranged acute leukemias

(2008) J. Faber et al.   BLOOD

A role for MEIS1 in MLL-fusion gene leukemia

(2008) A. R. Kumar et al.   BLOOD

Abundant anti-apoptotic BCL-2 is a molecular target in leukaemias with t(4;11) translocation

(2008) Blaine W. Robinson et al.   BRITISH JOURNAL OF HAEMATOLOGY

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

Microenvironment Determines Lineage Fate in a Human Model of MLL-AF9 Leukemia

(2008) Junping Wei et al.   CANCER CELL

Loss of MLL PHD Finger 3 Is Necessary for MLL-ENL-Induced Hematopoietic Stem Cell Immortalization

(2008) J. Chen et al.   CANCER RESEARCH

MLLT3 Regulates Early Human Erythroid and Megakaryocytic Cell Fate

(2008) Cristina Pina et al.   Cell Stem Cell

Clinical features and outcome of MLL gene rearranged acute lymphoblastic leukemia in infants with additional chromosomal abnormalities other than 11q23 translocation

(2008) Hisamichi Tauchi et al.   LEUKEMIA RESEARCH

Chemically ubiquitylated histone H2B stimulates hDot1L-mediated intranucleosomal methylation

(2008) Robert K. McGinty et al.   NATURE

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