Cited by 199Acute Myeloid Leukemia ResearchCancer-related Molecular PathwaysRetinoids in leukemia and cellular processes
Targeting IRAK1 as a therapeutic approach for myelodysplastic syndrome
Open accessRhyasen, Garrett W., Bolanos, Lyndsey, Fang, Jing, Jerez, Andres, Wunderlich, Mark, Rigolino, Carmela, Mathews, Lesley, Ferrer, Marc +11 more·2013·Cancer Cell
Abstract
Myelodysplastic syndromes (MDSs) arise from a defective hematopoietic stem/progenitor cell. Consequently, there is an urgent need to develop targeted therapies capable of eliminating the MDS-initiating clones. We identified that IRAK1, an immune-modulating kinase, is overexpressed and hyperactivated in MDSs. MDS clones treated with a small molecule IRAK1 inhibitor (IRAK1/4-Inh) exhibited impaired expansion and increased apoptosis, which coincided with TRAF6/NF-κB inhibition. Suppression of IRAK1, either by RNAi or with IRAK1/4-Inh, is detrimental to MDS cells, while sparing normal CD34(+) cells. Based on an integrative gene expression analysis, we combined IRAK1 and BCL2 inhibitors and found that cotreatment more effectively eliminated MDS clones. In summary, these findings implicate IRAK1 as a drugable target in MDSs.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Crossref · 10.1016/j.ccr.2013.05.006
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Blockade of these pathways can limit and/or reverse disease progression.
“blockade of these pathways can limit and/or reverse disease progression (Carey et al., 2017; Mitchell et al., 2018; Rhyasen et al., 2013; Zhang et al., 2016)”
From PU.1 enforces quiescence and limits hematopoietic stem cell expansion during inflammatory stress (2021) · cites this paper as Rhyasen et al., 2013
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 46 · Cited by 199
Research works printed but not linked: 40
- Bar M Stirewalt D Pogosova-Agadjanyan E Wagner V Gooley T Abbasi N Bhatia R Deeg HJ Radich J Gene expression patterns in myelodyplasia underline the role of apoptosis and differentiation in disease initiation and progression Translational oncogenomics 2008 3 137 149 20396593 PMC2854514
- Barreyro L Will B Bartholdy B Zhou L Todorova TI Stanley RF Ben-Neriah S Montagna C Parekh S Pellagatti A Overexpression of interleukin 1 receptor accessory protein in stem and progenitor cells and outcome correlation in AML and MDS Blood 2012 PMC3418722 22723552
- Boldin MP Taganov KD Rao DS Yang L Zhao JL Kalwani M Garcia-Flores Y Luong M Devrekanli A Xu J miR-146a is a significant brake on autoimmunity, myeloproliferation, and cancer in mice J Exp Med 2011 208 1189 1201 21555486 PMC3173243
- Breccia M Alimena G NF-kappaB as a potential therapeutic target in myelodysplastic syndromes and acute myeloid leukemia Expert opinion on therapeutic targets 2010 14 1157 1176 20858024
- Camos M Esteve J Jares P Colomer D Rozman M Villamor N Costa D Carrio A Nomdedeu J Montserrat E Campo E Gene expression profiling of acute myeloid leukemia with translocation t(8;16)(p11;p13) and MYST3-CREBBP rearrangement reveals a distinctive signature with a specific pattern of HOX gene expression Cancer Res 2006 66 6947 6954 16849538
- Chen G Zeng W Miyazato A Billings E Maciejewski JP Kajigaya S Sloand EM Young NS Distinctive gene expression profiles of CD34 cells from patients with myelodysplastic syndrome characterized by specific chromosomal abnormalities Blood 2004 104 4210 4218 15315976
- Chen J Bardes EE Aronow BJ Jegga AG ToppGene Suite for gene list enrichment analysis and candidate gene prioritization Nucleic Acids Res 2009 37 W305 W311 19465376 PMC2703978
- Conze DB Wu CJ Thomas JA Landstrom A Ashwell JD Lys63-linked polyubiquitination of IRAK-1 is required for interleukin-1 receptor- and toll-like receptor-mediated NF-kappaB activation Mol Cell Biol 2008 28 3538 3547 18347055 PMC2423148
- Corey SJ Minden MD Barber DL Kantarjian H Wang JC Schimmer AD Myelodysplastic syndromes: the complexity of stem-cell diseases Nat Rev Cancer 2007 7 118 129 17251918
- Ebert BL Preface. The biology and treatment of myelodysplastic syndrome Hematology/oncology clinics of North America 2010 24 xiii xvi 20359625
- Fang J Rhyasen G Bolanos L Rasch C Varney M Wunderlich M Goyama S Jansen G Cloos J Rigolino C Cytotoxic effects of bortezomib in myelodysplastic syndrome/acute myeloid leukemia depend on autophagy-mediated lysosomal degradation of TRAF6 and repression of PSMA1 Blood 2012 PMC3412348 22685174
- Flannery S Bowie AG The interleukin-1 receptor-associated kinases: critical regulators of innate immune signalling Biochem Pharmacol 2011 80 1981 1991 20599782
- Gondek LP Tiu R O'Keefe CL Sekeres MA Theil KS Maciejewski JP Chromosomal lesions and uniparental disomy detected by SNP arrays in MDS, MDS/MPD, and MDS-derived AML Blood 2008 111 1534 1542 17954704 PMC2214746
- Greenberg PL Current therapeutic approaches for patients with myelodysplastic syndromes Br J Haematol 2010 150 131 143 20507314
- Hofmann WK de Vos S Komor M Hoelzer D Wachsman W Koeffler HP Characterization of gene expression of CD34+ cells from normal and myelodysplastic bone marrow Blood 2002 100 3553 3560 12411319
- Kollewe C Mackensen AC Neumann D Knop J Cao P Li S Wesche H Martin MU Sequential autophosphorylation steps in the interleukin-1 receptor-associated kinase-1 regulate its availability as an adapter in interleukin-1 signaling J Biol Chem 2004 279 5227 5236 14625308
- Kristinsson SY Bjorkholm M Hultcrantz M Derolf AR Landgren O Goldin LR Chronic immune stimulation might act as a trigger for the development of acute myeloid leukemia or myelodysplastic syndromes J Clin Oncol 2011 29 2897 2903 21690473 PMC3138717
- Martin MG Welch JS Uy GL Fehniger TA Kulkarni S Duncavage EJ Walter MJ Limited engraftment of low-risk myelodysplastic syndrome cells in NOD/SCID gamma-C chain knockout mice Leukemia 2011 24 1662 1664 20668474 PMC3341627
- Matsuoka A Tochigi A Kishimoto M Nakahara T Kondo T Tsujioka T Tasaka T Tohyama Y Tohyama K Lenalidomide induces cell death in an MDS-derived cell line with deletion of chromosome 5q by inhibition of cytokinesis Leukemia 2010 24 748 755 20130600
- Ngo VN Young RM Schmitz R Jhavar S Xiao W Lim KH Kohlhammer H Xu W Yang Y Zhao H Oncogenically active MYD88 mutations in human lymphoma Nature 2010 470 115 119 21179087 PMC5024568
- Nimer SD Myelodysplastic syndromes Blood 2008 111 4841 4851 18467609
- O'Dwyer ME Mauro MJ Druker BJ STI571 as a targeted therapy for CML Cancer Invest 2003 21 429 438 12901289
- Pellagatti A Cazzola M Giagounidis A Perry J Malcovati L Della Porta MG Jadersten M Killick S Verma A Norbury CJ Deregulated gene expression pathways in myelodysplastic syndrome hematopoietic stem cells Leukemia 2010 24 756 764 20220779
- Powers JP Li S Jaen JC Liu J Walker NP Wang Z Wesche H Discovery and initial SAR of inhibitors of interleukin-1 receptor-associated kinase-4 Bioorg Med Chem Lett 2006 16 2842 2845 16563752
- Sekeres MA Are we nearer to curing patients with MDS? Best Pract Res Clin Haematol 2010a 23 481 487 21130411
- Sekeres MA The epidemiology of myelodysplastic syndromes Hematology/oncology clinics of North America 2010b 24 287 294 20359626
- Sokol L Caceres G Volinia S Alder H Nuovo GJ Liu CG McGraw K Clark JA Sigua CA Chen DT Identification of a risk dependent microRNA expression signature in myelodysplastic syndromes Br J Haematol 2011 153 24 32 21332710 PMC4294220
- Starczynowski DT Karsan A Innate immune signaling in the myelodysplastic syndromes Hematol Oncol Clin North Am 2010 24 343 359 20359630
- Starczynowski DT Kuchenbauer F Argiropoulos B Sung S Morin R Muranyi A Hirst M Hogge D Marra M Wells RA Identification of miR-145 and miR-146a as mediators of the 5q- syndrome phenotype Nat Med 2010 16 49 58 19898489
- Starczynowski DT Kuchenbauer F Wegrzyn J Rouhi A Petriv O Hansen CL Humphries RK Karsan A MicroRNA-146a disrupts hematopoietic differentiation and survival Exp Hematol 2011a 39 167 178 e164 20933052
- Starczynowski DT Morin R McPherson A Lam J Chari R Wegrzyn J Kuchenbauer F Hirst M Tohyama K Humphries RK Genome-wide identification of human microRNAs located in leukemia-associated genomic alterations Blood 2011b 117 595 607 20962326
- Tehranchi R Woll PS Anderson K Buza-Vidas N Mizukami T Mead AJ Astrand-Grundstrom I Strombeck B Horvat A Ferry H Persistent malignant stem cells in del(5q) myelodysplasia in remission N Engl J Med 2010 363 1025 1037 20825315
- Thomadaki H Scorilas A Molecular profile of the BCL2 family of the apoptosis related genes in breast cancer cells after treatment with cytotoxic/cytostatic drugs Connect Tissue Res 2008 49 261 264 18661356
- Tohyama K Tohyama Y Nakayama T Ueda T Nakamura T Yoshida Y A novel factor-dependent human myelodysplastic cell line, MDS92, contains haemopoietic cells of several lineages Br J Haematol 1995 91 795 799 8547120
- Vanderwerf SM Svahn J Olson S Rathbun RK Harrington C Yates J Keeble W Anderson DC Anur P Pereira NF TLR8-dependent TNF-(alpha) overexpression in Fanconi anemia group C cells Blood 2009 114 5290 5298 19850743 PMC2796134
- Vasikova A Belickova M Budinska E Cermak J A distinct expression of various gene subsets in CD34+ cells from patients with early and advanced myelodysplastic syndrome Leuk Res 2010 34 1566 1572 20303173
- Wang Z Wesche H Stevens T Walker N Yeh WC IRAK-4 inhibitors for inflammation Curr Top Med Chem 2009 9 724 737 19689377 PMC3182414
- Wunderlich M Chou FS Link KA Mizukawa B Perry RL Carroll M Mulloy JC AML xenograft efficiency is significantly improved in NOD/SCID-IL2RG mice constitutively expressing human SCF, GM-CSF and IL-3 Leukemia 2010 24 1785 1788 20686503 PMC5439963
- Yang YF Chen Z Hu SL Hu J Li B Li JT Wei LJ Qian ZM Lin JK Feng H Zhu G Interleukin-1 receptor associated kinases-1/4 inhibition protects against acute hypoxia/ischemia-induced neuronal injury in vivo and in vitro Neuroscience 2011 196 25 34 21925238
- Zhao JL Rao DS Boldin MP Taganov KD O'Connell RM Baltimore D NF-kappaB dysregulation in microRNA-146a-deficient mice drives the development of myeloid malignancies Proc Natl Acad Sci U S A 2011 108 9184 9189 21576471 PMC3107319
- Authors
- Rhyasen, G. W., Bolanos, L., Fang, J., Jerez, A., Wunderlich, M., Rigolino, C., Mathews, L., Ferrer, M., Southall, N., Guha, R., Keller, J., Thomas, C., Beverly, L. J., Cortelezzi, A., Oliva, E. N., Cuzzola, M., Maciejewski, J. P., Mulloy, J. C., & Starczynowski, D. T.
- Affiliations
- Cincinnati Children's Hospital Medical Center (US)
- Azienda ospedaliera "Bianchi-Melacrino-Morelli" (IT)
- National Institutes of Health (US)
- University of Louisville (US)
- University of Milan (IT)
- Cleveland Clinic (US)
- Corresponding author
- Starczynowski, Daniel T.
- ORCID
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2013-07
- Volume
- 24
- Issue
- 1
- Pages
- 90-104
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC3711103
- OpenAlex
- W2018317651
- Cited by
- 199
- References
- 46
- Citations by year
- 2026: 7 · 2025: 16 · 2024: 8 · 2023: 10 · 2022: 9 · 2021: 21 · 2020: 20 · 2019: 17 · 2018: 23 · 2017: 15 · 2016: 14 · 2015: 19 · 2014: 14 · 2013: 6
- FWCI
- 11.49
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UL1TR000077)
- National Heart, Lung, and Blood Institute (R01HL111103)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK090971)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Keywords
- myelodysplastic syndrome, IRAK1, TRAF6, NF-κB signaling, BCL-2 inhibitor, hematopoietic stem and progenitor cells, apoptosis, targeted therapy
- MeSH terms
- Animals, Cell Line, Humans, Myelodysplastic Syndromes, Phosphorylation, NF-kappa B, Apoptosis, Proto-Oncogene Proteins c-bcl-2, Gene Expression Profiling, Xenograft Model Antitumor Assays, TNF Receptor-Associated Factor 6, Mice, Interleukin-1 Receptor-Associated Kinases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
