IRAK1 and IRAK4 as emerging therapeutic targets in hematologic malignancies

Targeting the IRAK1-S100A9 Axis Overcomes Resistance to Paclitaxel in Nasopharyngeal Carcinoma

(2021) Lizhen Liu et al.   CANCER RESEARCH

Chemotherapy induces senescence-like resilient cells capable of initiating AML recurrence

(2021) Cihangir Duy et al.   Cancer Discovery

Sequential CRISPR gene editing in human iPSCs charts the clonal evolution of myeloid leukemia and identifies early disease targets

(2021) Tiansu Wang et al.   Cell Stem Cell

Inhibition of IRAK1/4 enhances the antitumor effect of lenvatinib in anaplastic thyroid cancer cells

(2021) Yoshifumi Kawamura et al.   CANCER SCIENCE

Innate immune pathways and inflammation in hematopoietic aging, clonal hematopoiesis, and MDS

(2021) Jennifer J. Trowbridge et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Discovery of Highly Potent and Selective IRAK1 Degraders to Probe Scaffolding Functions of IRAK1 in ABC DLBCL

(2021) Liqiang Fu et al.   JOURNAL OF MEDICINAL CHEMISTRY

SMARCA4 oncogenic potential via IRAK1 enhancer to activate Gankyrin and AKR1B10 in liver cancer

(2021) Sang Yean Kim et al.   ONCOGENE

Therapeutic targeting of the inflammasome in myeloid malignancies

(2021) Samarpana Chakraborty et al.   Blood Cancer Journal

MyD88 Death-Domain Oligomerization Determines Myddosome Architecture: Implications for Toll-like Receptor Signaling

(2020) Martin C. Moncrieffe et al.   STRUCTURE

Glucocorticoids enhance the anti-leukemic activity of FLT3 inhibitors in FLT3 mutant acute myeloid leukemia

(2020) Melat T. Gebru et al.   BLOOD

Targeting AML-associated FLT3 mutations with a type I kinase inhibitor

(2020) LaQuita M. Jones et al.   JOURNAL OF CLINICAL INVESTIGATION

The Nlrp3 inflammasome as a “rising star” in studies of normal and malignant hematopoiesis

(2020) Mariusz Z. Ratajczak et al.   LEUKEMIA

Adaptive response to inflammation contributes to sustained myelopoiesis and confers a competitive advantage in myelodysplastic syndrome HSCs

(2020) Tomoya Muto et al.   NATURE IMMUNOLOGY

Oncogenic KrasG12D causes myeloproliferation via NLRP3 inflammasome activation

(2020) Shaima’a Hamarsheh et al.   Nature Communications

TPL2 enforces RAS-induced inflammatory signaling and is activated by point mutations

(2020) Paarth B. Dodhiawala et al.   JOURNAL OF CLINICAL INVESTIGATION

S100A14 suppresses metastasis of nasopharyngeal carcinoma by inhibition of NF-kB signaling through degradation of IRAK1

(2020) Dong-Fang Meng et al.   ONCOGENE

Contribution of Aberrant Toll Like Receptor Signaling to the Pathogenesis of Myelodysplastic Syndromes

(2020) Luana Chiquetto Paracatu et al.   Frontiers in Immunology

Discovery of Proteolysis-Targeting Chimera Molecules that Selectively Degrade the IRAK3 Pseudokinase

(2020) Sébastien L. Degorce et al.   JOURNAL OF MEDICINAL CHEMISTRY

Myelodysplastic Syndromes

(2020) Mario Cazzola   NEW ENGLAND JOURNAL OF MEDICINE

Discovery of a Selective, Covalent IRAK1 Inhibitor with Antiproliferative Activity in MYD88 Mutated B-Cell Lymphoma

(2020) John M. Hatcher et al.   ACS Medicinal Chemistry Letters

miR-146b-5p Enhances the Sensitivity of NSCLC to EGFR Tyrosine Kinase Inhibitors by Regulating the IRAK1/NF-κB Pathway

(2020) Yi-Nan Liu et al.   Molecular Therapy-Nucleic Acids

Dimeric Structure of the Pseudokinase IRAK3 Suggests an Allosteric Mechanism for Negative Regulation

(2020) Sven M. Lange et al.   STRUCTURE

An IRAK1–PIN1 signalling axis drives intrinsic tumour resistance to radiation therapy

(2019) Peter H. Liu et al.   NATURE CELL BIOLOGY

The central role of inflammatory signaling in the pathogenesis of myelodysplastic syndromes

(2019) David A. Sallman et al.   BLOOD

Preclinical activity and a pilot phase I study of pacritinib, an oral JAK2/FLT3 inhibitor, and chemotherapy in FLT3-ITD-positive AML

(2019) Jae Yoon Jeon et al.   INVESTIGATIONAL NEW DRUGS

U2AF1 mutations induce oncogenic IRAK4 isoforms and activate innate immune pathways in myeloid malignancies

(2019) Molly A. Smith et al.   NATURE CELL BIOLOGY

Targeting IRAK4 disrupts inflammatory pathways and delays tumor development in chronic lymphocytic leukemia

(2019) Neus Giménez et al.   LEUKEMIA

Neutrophils deficient in innate suppressor IRAK-M enhances anti-tumor immune responses

(2019) Yao Zhang et al.   MOLECULAR THERAPY

Overcoming adaptive therapy resistance in AML by targeting immune response pathways

(2019) Katelyn Melgar et al.   Science Translational Medicine

SF3B1 Mutations Induce Oncogenic IRAK4 Isoforms and Activate Targetable Innate Immune Pathways in MDS and AML

(2019) Gaurav S Choudhary et al.   BLOOD

The Oral JAK2/IRAK1 Inhibitor Pacritinib Demonstrates Spleen Volume Reduction in Myelofibrosis Patients Independent of JAK2V617F Allele Burden

(2019) Srdan Verstovsek et al.   BLOOD

IRAK3 modulates downstream innate immune signalling through its guanylate cyclase activity

(2019) L. A. Freihat et al.   Scientific Reports

Tumor–Stroma IL1β-IRAK4 Feedforward Circuitry Drives Tumor Fibrosis, Chemoresistance, and Poor Prognosis in Pancreatic Cancer

(2018) Daoxiang Zhang et al.   CANCER RESEARCH

IRAK1 Augments Cancer Stemness and Drug Resistance via the AP-1/AKR1B10 Signaling Cascade in Hepatocellular Carcinoma

(2018) Bowie Y. Cheng et al.   CANCER RESEARCH

IRAK2 counterbalances oncogenic Smurf1 in colon cancer cells by dictating ER stress

(2018) Jingwen Liu et al.   CELLULAR SIGNALLING

Genetic variant of IRAK2 in the toll-like receptor signaling pathway and survival of non-small cell lung cancer

(2018) Yinghui Xu et al.   INTERNATIONAL JOURNAL OF CANCER

Expression of microRNAs and IRAK1 pathway genes are altered in gastric cancer patients with Helicobacter pylori infection

(2018) Reza Ranjbar et al.   JOURNAL OF CELLULAR BIOCHEMISTRY

Inhibition of interleukin-1 receptor-associated kinase-1 is a therapeutic strategy for acute myeloid leukemia subtypes

(2018) Mona M. Hosseini et al.   LEUKEMIA

A multiprotein supercomplex controlling oncogenic signalling in lymphoma

(2018) James D. Phelan et al.   NATURE

The E3 ubiquitin ligase Pellino2 mediates priming of the NLRP3 inflammasome

(2018) Fiachra Humphries et al.   Nature Communications

Disordered Immune Regulation and its Therapeutic Targeting in Myelodysplastic Syndromes

(2018) Kathryn S. Ivy et al.   Current Hematologic Malignancy Reports

TLR Signaling Is Activated in Lymph Node–Resident CLL Cells and Is Only Partially Inhibited by Ibrutinib

(2018) Eman L. Dadashian et al.   CANCER RESEARCH

Tet2 restrains inflammatory gene expression in macrophages

(2017) Alyssa H. Cull et al.   EXPERIMENTAL HEMATOLOGY

IRAK4 kinase activity controls Toll-like receptor–induced inflammation through the transcription factor IRF5 in primary human monocytes

(2017) Leah Cushing et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Discovery and Optimization of Pyrrolopyrimidine Inhibitors of Interleukin-1 Receptor Associated Kinase 4 (IRAK4) for the Treatment of Mutant MYD88L265P Diffuse Large B-Cell Lymphoma

(2017) James S. Scott et al.   JOURNAL OF MEDICINAL CHEMISTRY

Chromosome 1q21.3 amplification is a trackable biomarker and actionable target for breast cancer recurrence

(2017) Jian Yuan Goh et al.   NATURE MEDICINE

Crystal structure of human IRAK1

(2017) Li Wang et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Diagnostic and prognostic roles of IRAK1 in hepatocellular carcinoma tissues: an analysis of immunohistochemistry and RNA-sequencing data from the cancer genome atlas

(2017) Zhi-hua Ye et al.   OncoTargets and Therapy

Identification of Interleukin-1 by Functional Screening as a Key Mediator of Cellular Expansion and Disease Progression in Acute Myeloid Leukemia

(2017) Alyssa Carey et al.   Cell Reports

IRAK2 directs stimulus-dependent nuclear export of inflammatory mRNAs

(2017) Hao Zhou et al.   eLife

The NLRP3 inflammasome functions as a driver of the myelodysplastic syndrome phenotype

(2016) A. A. Basiorka et al.   BLOOD

Mesenchymal Inflammation Drives Genotoxic Stress in Hematopoietic Stem Cells and Predicts Disease Evolution in Human Pre-leukemia

(2016) Noemi A. Zambetti et al.   Cell Stem Cell

Constitutive IRAK4 Activation Underlies Poor Prognosis and Chemoresistance in Pancreatic Ductal Adenocarcinoma

(2016) Daoxiang Zhang et al.   CLINICAL CANCER RESEARCH

Epistasis between TIFAB and miR-146a: neighboring genes in del(5q) myelodysplastic syndrome

(2016) M E Varney et al.   LEUKEMIA

Ubiquitination of hnRNPA1 by TRAF6 links chronic innate immune signaling with myelodysplasia

(2016) Jing Fang et al.   NATURE IMMUNOLOGY

Rps14 haploinsufficiency causes a block in erythroid differentiation mediated by S100A8 and S100A9

(2016) Rebekka K Schneider et al.   NATURE MEDICINE

Comprehensive RNAi-based screening of human and mouse TLR pathways identifies species-specific preferences in signaling protein use

(2016) Jing Sun et al.   Science Signaling

Mechanism and Regulation of NLRP3 Inflammasome Activation

(2016) Yuan He et al.   TRENDS IN BIOCHEMICAL SCIENCES

Sensitizing leukemia stem cells to NF-κB inhibitor treatment in vivo by inactivation of both TNF and IL-1 signaling

(2016) Jing Li et al.   Oncotarget

Comprehensive RNAi-based screening of human and mouse TLR pathways identifies species-specific preferences in signaling protein use

(2016) Jing Sun et al.   Science Signaling

The Role of Toll-Like Receptors in Hematopoietic Malignancies

(2016) Darlene A. Monlish et al.   Frontiers in Immunology

Unraveling the Pathogenesis of MDS: The NLRP3 Inflammasome and Pyroptosis Drive the MDS Phenotype

(2016) David A. Sallman et al.   Frontiers in Oncology

Deconstructing innate immune signaling in myelodysplastic syndromes

(2015) Melinda E. Varney et al.   EXPERIMENTAL HEMATOLOGY

Toll-like receptor stimulation in splenic marginal zone lymphoma can modulate cell signaling, activation and proliferation

(2015) E. Fonte et al.   HAEMATOLOGICA

Inhibition of IRAK1/4 sensitizes T cell acute lymphoblastic leukemia to chemotherapies

(2015) Zhaoyang Li et al.   JOURNAL OF CLINICAL INVESTIGATION

Loss ofTifab, a del(5q) MDS gene, alters hematopoiesis through derepression of Toll-like receptor–TRAF6 signaling

(2015) Melinda E. Varney et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Deregulation of innate immune and inflammatory signaling in myelodysplastic syndromes

(2015) I Gañán-Gómez et al.   LEUKEMIA

Methylation ofIRAK3is a novel prognostic marker in hepatocellular carcinoma

(2015) Chih-Chi Kuo   WORLD JOURNAL OF GASTROENTEROLOGY

IRAK1 is a therapeutic target that drives breast cancer metastasis and resistance to paclitaxel

(2015) Zhen Ning Wee et al.   Nature Communications

Targeting IRAK1 in T-cell acute lymphoblastic leukemia

(2015) Charles Dussiau et al.   Oncotarget

IRAK1 is a novel DEK transcriptional target and is essential for head and neck cancer cell survival

(2015) Allie K. Adams et al.   Oncotarget

Toll-like receptor stimulation in splenic marginal zone lymphoma can modulate cell signaling, activation and proliferation

(2015) E. Fonte et al.   HAEMATOLOGICA

Expansion of myeloid derived suppressor cells correlates with number of T regulatory cells and disease progression in myelodysplastic syndrome

(2015) Astrid Olsnes Kittang et al.   OncoImmunology

Mutations in TLR/MYD88 pathway identify a subset of young chronic lymphocytic leukemia patients with favorable outcome

(2014) A. Martinez-Trillos et al.   BLOOD

The structure function of the death domain of human IRAK-M

(2014) Jiangfeng Du et al.   Cell Communication and Signaling

A Coding IRAK2 Protein Variant Compromises Toll-like receptor (TLR) Signaling and Is Associated with Colorectal Cancer Survival

(2014) Hui Wang et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Proinflammatory S100 Proteins Regulate the Accumulation of Myeloid-Derived Suppressor Cells

(2014) P. Sinha et al.   JOURNAL OF IMMUNOLOGY

IRAK4 Dimerization and trans -Autophosphorylation Are Induced by Myddosome Assembly

(2014) Ryan Ferrao et al.   MOLECULAR CELL

Interleukin 1 receptor-associated kinase 1 (IRAK1) mutation is a common, essential driver for Kaposi sarcoma herpesvirus lymphoma

(2014) D. Yang et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Myeloid Malignancies with Chromosome 5q Deletions Acquire a Dependency on an Intrachromosomal NF-κB Gene Network

(2014) Jing Fang et al.   Cell Reports

Whole-genome integrative analysis reveals expression signatures predicting transformation in follicular lymphoma

(2013) M. Brodtkorb et al.   BLOOD

MYD88 L265P mutation in Waldenstrom macroglobulinemia

(2013) S. Poulain et al.   BLOOD

Targeting IRAK1 as a Therapeutic Approach for Myelodysplastic Syndrome

(2013) Garrett W. Rhyasen et al.   CANCER CELL

Evolution and Impact of Subclonal Mutations in Chronic Lymphocytic Leukemia

(2013) Dan A. Landau et al.   CELL

IRAK-M mediates Toll-like receptor/IL-1R-induced NFκB activation and cytokine production

(2013) Hao Zhou et al.   EMBO JOURNAL

Induction of myelodysplasia by myeloid-derived suppressor cells

(2013) Xianghong Chen et al.   JOURNAL OF CLINICAL INVESTIGATION

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

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

Cutting Edge: TLR Signaling Licenses IRAK1 for Rapid Activation of the NLRP3 Inflammasome

(2013) T. Fernandes-Alnemri et al.   JOURNAL OF IMMUNOLOGY

Two Phases of Inflammatory Mediator Production Defined by the Study of IRAK2 and IRAK1 Knock-in Mice

(2013) E. Pauls et al.   JOURNAL OF IMMUNOLOGY

Toll-like receptor alterations in myelodysplastic syndrome

(2013) Y Wei et al.   LEUKEMIA

Overexpression of the Toll-Like Receptor (TLR) Signaling Adaptor MYD88, but Lack of Genetic Mutation, in Myelodysplastic Syndromes

(2013) Sophie Dimicoli et al.   PLoS One

IRAK-1 bypasses priming and directly links TLRs to rapid NLRP3 inflammasome activation

(2013) K.-M. Lin et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Activation of the canonical IKK complex by K63/M1-linked hybrid ubiquitin chains

(2013) C. H. Emmerich et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Augmentation of Therapeutic Responses in Melanoma by Inhibition of IRAK-1,-4

(2012) R. Srivastava et al.   CANCER RESEARCH

MYD88 L265P Somatic Mutation in Waldenström's Macroglobulinemia

(2012) Steven P. Treon et al.   NEW ENGLAND JOURNAL OF MEDICINE

Triggering of toll-like receptor-4 in human multiple myeloma cells promotes proliferation and alters cell responses to immune and chemotherapy drug attack

(2011) Hanying Bao et al.   CANCER BIOLOGY & THERAPY

Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia

(2011) Xose S. Puente et al.   NATURE

TGF-β-induced IRAK-M expression in tumor-associated macrophages regulates lung tumor growth

(2011) T J Standiford et al.   ONCOGENE

NF- B dysregulation in microRNA-146a-deficient mice drives the development of myeloid malignancies

(2011) J. L. Zhao et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Deregulated gene expression pathways in myelodysplastic syndrome hematopoietic stem cells

(2010) A Pellagatti et al.   LEUKEMIA

Oncogenically active MYD88 mutations in human lymphoma

(2010) Vu N. Ngo et al.   NATURE

Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma

(2010) R. Eric Davis et al.   NATURE

Helical assembly in the MyD88–IRAK4–IRAK2 complex in TLR/IL-1R signalling

(2010) Su-Chang Lin et al.   NATURE

Expression of toll-like receptor-9 is increased in poorly differentiated prostate tumors

(2010) Marja-Riitta Väisänen et al.   PROSTATE

Expression of Interleukin-1 Receptor-Associated Kinase-1 in Non-Small Cell Lung Carcinoma and Preneoplastic Lesions

(2009) C. Behrens et al.   CLINICAL CANCER RESEARCH

Interleukin-1 Receptor-associated Kinase 2 Is Critical for Lipopolysaccharide-mediated Post-transcriptional Control

(2009) Youzhong Wan et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Induction of a Chronic Disease State in Patients With Smoldering or Indolent Multiple Myeloma by Targeting Interleukin 1β-Induced Interleukin 6 Production and the Myeloma Proliferative Component

(2009) John A. Lust et al.   MAYO CLINIC PROCEEDINGS

The kinase activities of interleukin-1 receptor associated kinase (IRAK)-1 and 4 are redundant in the control of inflammatory cytokine expression in human cells

(2009) Kyung W. Song et al.   MOLECULAR IMMUNOLOGY

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

(2009) Daniel T Starczynowski et al.   NATURE MEDICINE

Inhibition of dendritic cell differentiation and accumulation of myeloid-derived suppressor cells in cancer is regulated by S100A9 protein

(2008) Pingyan Cheng et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Lys63-Linked Polyubiquitination of IRAK-1 Is Required for Interleukin-1 Receptor- and Toll-Like Receptor-Mediated NF- B Activation

(2008) D. B. Conze et al.   MOLECULAR AND CELLULAR BIOLOGY

Sequential control of Toll-like receptor–dependent responses by IRAK1 and IRAK2

(2008) Tatsukata Kawagoe et al.   NATURE IMMUNOLOGY