CoChat
Sign Up
Cited by 97Acute Myeloid Leukemia ResearchRetinoids in leukemia and cellular processesFlavonoids in Medical Research

IL1RAP potentiates multiple oncogenic signaling pathways in AML

Open access
Mitchell, Kelly, Barreyro, Laura, Todorova, Tihomira I., Taylor, Samuel J., Antony-Debré, Iléana, Narayanagari, Swathi-Rao, Carvajal, Luis A., Leite, Joana +7 more·2018·Journal of Experimental Medicine
DOI 10.1084/jem.20180147PMC PMC5987926
Open this paper in CoChat — free accountOpen PDF

Abstract

The surface molecule interleukin-1 receptor accessory protein (IL1RAP) is consistently overexpressed across multiple genetic subtypes of acute myeloid leukemia (AML) and other myeloid malignancies, including at the stem cell level, and is emerging as a novel therapeutic target. However, the cell-intrinsic functions of IL1RAP in AML cells are largely unknown. Here, we show that targeting of IL1RAP via RNA interference, genetic deletion, or antibodies inhibits AML pathogenesis in vitro and in vivo, without perturbing healthy hematopoietic function or viability. Furthermore, we found that the role of IL1RAP is not restricted to the IL-1 receptor pathway, but that IL1RAP physically interacts with and mediates signaling and pro-proliferative effects through FLT3 and c-KIT, two receptor tyrosine kinases with known key roles in AML pathogenesis. Our study provides a new mechanistic basis for the efficacy of IL1RAP targeting in AML and reveals a novel role for this protein in the pathogenesis of the disease.

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.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1084/jem.20180147

Cites

5 of 5 references verified0 citation errors · 0 not checkable

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.

A few free checks a day · papers already verified open instantly · results are public

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?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 66

  1. Ågerstam H., Karlsson C., Hansen N., Sandén C., Askmyr M., von Palffy S., Högberg C., Rissler M., Wunderlich M., Juliusson G., 2015 Antibodies targeting human IL1RAP (IL1R3) show therapeutic effects in xenograft models of acute myeloid leukemia. Proc. Natl. Acad. Sci. USA. 112: 10786– 10791. 10.1073/pnas.1422749112 26261316 PMC4553807 · DOI
  2. Ågerstam H., Hansen N., von Palffy S., Sandén C., Reckzeh K., Karlsson C., Lilljebjörn H., Landberg N., Askmyr M., Högberg C., 2016 IL1RAP antibodies block IL-1-induced expansion of candidate CML stem cells and mediate cell killing in xenograft models. Blood. 128: 2683– 2693. 10.1182/blood-2015-11-679985 27621309 · DOI · Paper page
  3. Ali S., Huber M., Kollewe C., Bischoff S.C., Falk W., and Martin M.U. 2007 IL-1 receptor accessory protein is essential for IL-33-induced activation of T lymphocytes and mast cells. Proc. Natl. Acad. Sci. USA. 104: 18660– 18665. 10.1073/pnas.0705939104 18003919 PMC2141833 · DOI
  4. Askmyr M., Ågerstam H., Hansen N., Gordon S., Arvanitakis A., Rissler M., Juliusson G., Richter J., Järås M., and Fioretos T. 2013 Selective killing of candidate AML stem cells by antibody targeting of IL1RAP. Blood. 121: 3709– 3713. 10.1182/blood-2012-09-458935 23479569 · DOI · Paper page
  5. Barreyro L., Will B., Bartholdy B., Zhou L., Todorova T.I., Stanley R.F., Ben-Neriah S., Montagna C., Parekh S., Pellagatti A., 2012 Overexpression of IL-1 receptor accessory protein in stem and progenitor cells and outcome correlation in AML and MDS. Blood. 120: 1290– 1298. 10.1182/blood-2012-01-404699 22723552 PMC3418722 · DOI · Paper page
  6. Batard P., Szollosi J., Luescher I., Cerottini J.C., MacDonald R., and Romero P. 2002 Use of phycoerythrin and allophycocyanin for fluorescence resonance energy transfer analyzed by flow cytometry: advantages and limitations. Cytometry. 48: 97– 105. 10.1002/cyto.10106 12116371 · DOI
  7. Baum C.M., Weissman I.L., Tsukamoto A.S., Buckle A.M., and Peault B. 1992 Isolation of a candidate human hematopoietic stem-cell population. Proc. Natl. Acad. Sci. USA. 89: 2804– 2808. 10.1073/pnas.89.7.2804 1372992 PMC48751 · DOI
  8. Blumberg H., Dinh H., Trueblood E.S., Pretorius J., Kugler D., Weng N., Kanaly S.T., Towne J.E., Willis C.R., Kuechle M.K., 2007 Opposing activities of two novel members of the IL-1 ligand family regulate skin inflammation. J. Exp. Med. 204: 2603– 2614. 10.1084/jem.20070157 17908936 PMC2118475 · DOI
  9. Bonnet D., and Dick J.E. 1997 Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat. Med. 3: 730– 737. 10.1038/nm0797-730 9212098 · DOI
  10. Brandts C.H., Sargin B., Rode M., Biermann C., Lindtner B., Schwäble J., Buerger H., Müller-Tidow C., Choudhary C., McMahon M., 2005 Constitutive activation of Akt by Flt3 internal tandem duplications is necessary for increased survival, proliferation, and myeloid transformation. Cancer Res. 65: 9643– 9650. 10.1158/0008-5472.CAN-05-0422 16266983 · DOI
  11. Choudhary C., Müller-Tidow C., Berdel W.E., and Serve H. 2005 Signal transduction of oncogenic Flt3. Int. J. Hematol. 82: 93– 99. 10.1532/IJH97.05090 16146838 · DOI
  12. Corces-Zimmerman M.R., Hong W.J., Weissman I.L., Medeiros B.C., and Majeti R. 2014 Preleukemic mutations in human acute myeloid leukemia affect epigenetic regulators and persist in remission. Proc. Natl. Acad. Sci. USA. 111: 2548– 2553. 10.1073/pnas.1324297111 24550281 PMC3932921 · DOI · Paper page
  13. Cullinan E.B., Kwee L., Nunes P., Shuster D.J., Ju G., McIntyre K.W., Chizzonite R.A., and Labow M.A. 1998 IL-1 receptor accessory protein is an essential component of the IL-1 receptor. J. Immunol. 161: 5614– 5620. 9820540
  14. Culver-Cochran A.E., and Starczynowski D.T. 2018 Chronic innate immune signaling results in ubiquitination of splicing machinery. Cell Cycle. Apr 3: 1– 3. 10.1080/15384101.2018.1429082 PMC5927646 29336715 · DOI
  15. Drube S., Heink S., Walter S., Löhn T., Grusser M., Gerbaulet A., Berod L., Schons J., Dudeck A., Freitag J., 2010 The receptor tyrosine kinase c-Kit controls IL-33 receptor signaling in mast cells. Blood. 115: 3899– 3906. 10.1182/blood-2009-10-247411 20200353 · DOI
  16. Dunne A., and O’Neill L.A. 2003 The interleukin-1 receptor/Toll-like receptor superfamily: signal transduction during inflammation and host defense. Sci. STKE. 2003: re3. 12606705
  17. Fang J., Bolanos L.C., Choi K., Liu X., Christie S., Akunuru S., Kumar R., Wang D., Chen X., Greis K.D., 2017 Ubiquitination of hnRNPA1 by TRAF6 links chronic innate immune signaling with myelodysplasia. Nat. Immunol. 18: 236– 245. 10.1038/ni.3654 28024152 PMC5423405 · DOI
  18. Förster T. 1948 Zwischenmolekulare Energiewanderung und Fluoreszenz. Ann. Phys. 437: 55– 75. 10.1002/andp.19484370105 · DOI · Paper page
  19. Gañán-Gómez I., Wei Y., Starczynowski D.T., Colla S., Yang H., Cabrero-Calvo M., Bohannan Z.S., Verma A., Steidl U., and Garcia-Manero G. 2015 Deregulation of innate immune and inflammatory signaling in myelodysplastic syndromes. Leukemia. 29: 1458– 1469. 10.1038/leu.2015.69 25761935 PMC4857136 · DOI · Paper page
  20. Gerber J.M., Gucwa J.L., Esopi D., Gurel M., Haffner M.C., Vala M., Nelson W.G., Jones R.J., and Yegnasubramanian S. 2013 Genome-wide comparison of the transcriptomes of highly enriched normal and chronic myeloid leukemia stem and progenitor cell populations. Oncotarget. 4: 715– 728. 10.18632/oncotarget.990 23651669 PMC3742832 · DOI
  21. Greenfeder S.A., Nunes P., Kwee L., Labow M., Chizzonite R.A., and Ju G. 1995 Molecular cloning and characterization of a second subunit of the interleukin 1 receptor complex. J. Biol. Chem. 270: 13757– 13765. 10.1074/jbc.270.23.13757 7775431 · DOI
  22. György Vereb P.N., and Szöllősi J. 2011 Flow Cytometry Protocols, Methods in Molecular Biology. In Flow Cytometric FRET Analysis of Protein Interaction. Hawley T., and Hawley R., editors. Humana Press, New York. 21 pp. 21116993
  23. Hemmati S., Haque T., and Gritsman K. 2017 Inflammatory Signaling Pathways in Preleukemic and Leukemic Stem Cells. Front. Oncol. 7: 265 10.3389/fonc.2017.00265 29181334 PMC5693908 · DOI
  24. Ho T.C., LaMere M., Stevens B.M., Ashton J.M., Myers J.R., O’Dwyer K.M., Liesveld J.L., Mendler J.H., Guzman M., Morrissette J.D., 2016 Evolution of acute myelogenous leukemia stem cell properties after treatment and progression. Blood. 128: 1671– 1678. 10.1182/blood-2016-02-695312 27421961 PMC5043124 · DOI
  25. Ikeda H., Kanakura Y., Tamaki T., Kuriu A., Kitayama H., Ishikawa J., Kanayama Y., Yonezawa T., Tarui S., and Griffin J.D. 1991 Expression and functional role of the proto-oncogene c-kit in acute myeloblastic leukemia cells. Blood. 78: 2962– 2968. 1720040
  26. Jan M., and Majeti R. 2013 Clonal evolution of acute leukemia genomes. Oncogene. 32: 135– 140. 10.1038/onc.2012.48 22349821 PMC5538364 · DOI
  27. Järås M., Johnels P., Hansen N., Agerstam H., Tsapogas P., Rissler M., Lassen C., Olofsson T., Bjerrum O.W., Richter J., and Fioretos T. 2010 Isolation and killing of candidate chronic myeloid leukemia stem cells by antibody targeting of IL-1 receptor accessory protein. Proc. Natl. Acad. Sci. USA. 107: 16280– 16285. 10.1073/pnas.1004408107 20805474 PMC2941341 · DOI
  28. Jiang P., Liu B.Y., Huang J., Lu J., Sharmili R., Mishra M., Zhao X., Lin J., Hsi E.D., and Junutula J.R. 2016. Proceedings of the 107th Annual Meeting of the American Association for Cancer Research. Abstr. 3337.
  29. Kalaitzidis D., and Neel B.G. 2008 Flow-cytometric phosphoprotein analysis reveals agonist and temporal differences in responses of murine hematopoietic stem/progenitor cells. PLoS One. 3: e3776 10.1371/journal.pone.0003776 19020663 PMC2582484 · DOI
  30. Kiyoi H., Naoe T., Nakano Y., Yokota S., Minami S., Miyawaki S., Asou N., Kuriyama K., Jinnai I., Shimazaki C., 1999 Prognostic implication of FLT3 and N-RAS gene mutations in acute myeloid leukemia. Blood. 93: 3074– 3080. 10216104
  31. Kiyoi H., Yanada M., and Ozekia K. 2005 Clinical significance of FLT3 in leukemia. Int. J. Hematol. 82: 85– 92. 10.1532/IJH97.05066 16146837 · DOI
  32. Landberg N., Hansen N., Askmyr M., Ågerstam H., Lassen C., Rissler M., Hjorth-Hansen H., Mustjoki S., Järås M., Richter J., and Fioretos T. 2016 IL1RAP expression as a measure of leukemic stem cell burden at diagnosis of chronic myeloid leukemia predicts therapy outcome. Leukemia. 30: 255– 258. 10.1038/leu.2015.135 26067823 · DOI
  33. Lapidot T., Sirard C., Vormoor J., Murdoch B., Hoang T., Caceres-Cortes J., Minden M., Paterson B., Caligiuri M.A., and Dick J.E. 1994 A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature. 367: 645– 648. 10.1038/367645a0 7509044 · DOI · Paper page
  34. Lee B.H., Tothova Z., Levine R.L., Anderson K., Buza-Vidas N., Cullen D.E., McDowell E.P., Adelsperger J., Fröhling S., Huntly B.J., 2007 FLT3 mutations confer enhanced proliferation and survival properties to multipotent progenitors in a murine model of chronic myelomonocytic leukemia. Cancer Cell. 12: 367– 380. 10.1016/j.ccr.2007.08.031 17936561 PMC2104473 · DOI
  35. Leung A.Y., Man C.H., and Kwong Y.L. 2013 FLT3 inhibition: a moving and evolving target in acute myeloid leukaemia. Leukemia. 27: 260– 268. 10.1038/leu.2012.195 22797419 · DOI
  36. Liang K., Volk A.G., Haug J.S., Marshall S.A., Woodfin A.R., Bartom E.T., Gilmore J.M., Florens L., Washburn M.P., Sullivan K.D., 2017 Therapeutic Targeting of MLL Degradation Pathways in MLL-Rearranged Leukemia. Cell. 168: 59– 72.e13. 10.1016/j.cell.2016.12.011 28065413 PMC5351781 · DOI
  37. Liang Y., Seymour R.E., and Sundberg J.P. 2011 Inhibition of NF-κB signaling retards eosinophilic dermatitis in SHARPIN-deficient mice. J. Invest. Dermatol. 131: 141– 149. 10.1038/jid.2010.259 20811394 PMC3071979 · DOI
  38. Lingel A., Weiss T.M., Niebuhr M., Pan B., Appleton B.A., Wiesmann C., Bazan J.F., and Fairbrother W.J. 2009 Structure of IL-33 and its interaction with the ST2 and IL-1RAcP receptors--insight into heterotrimeric IL-1 signaling complexes. Structure. 17: 1398– 1410. 10.1016/j.str.2009.08.009 19836339 PMC2766095 · DOI
  39. Lisovsky M., Estrov Z., Zhang X., Consoli U., Sanchez-Williams G., Snell V., Munker R., Goodacre A., Savchenko V., and Andreeff M. 1996 Flt3 ligand stimulates proliferation and inhibits apoptosis of acute myeloid leukemia cells: regulation of Bcl-2 and Bax. Blood. 88: 3987– 3997. 8916965
  40. McKeown M.R., Corces M.R., Eaton M.L., Fiore C., Lee E., Lopez J.T., Chen M.W., Smith D., Chan S.M., Koenig J.L., 2017 Superenhancer Analysis Defines Novel Epigenomic Subtypes of Non-APL AML, Including an RARα Dependency Targetable by SY-1425, a Potent and Selective RARα Agonist. Cancer Discov. 7: 1136– 1153. 10.1158/2159-8290.CD-17-0399 28729405 PMC5962349 · DOI
  41. O’Neill L.A. 2000 The interleukin-1 receptor/Toll-like receptor superfamily: signal transduction during inflammation and host defense. Sci. STKE. 2000: re1 10.1126/stke.2000.44.re1 11752602 · DOI
  42. O’Neill L.A. 2008 The interleukin-1 receptor/Toll-like receptor superfamily: 10 years of progress. Immunol. Rev. 226: 10– 18. 10.1111/j.1600-065X.2008.00701.x 19161412 · DOI
  43. Pandolfi A., Barreyro L., and Steidl U. 2013 Concise review: preleukemic stem cells: molecular biology and clinical implications of the precursors to leukemia stem cells. Stem Cells Transl. Med. 2: 143– 150. 10.5966/sctm.2012-0109 23349328 PMC3659760 · DOI
  44. Papaemmanuil E., Gerstung M., Bullinger L., Gaidzik V.I., Paschka P., Roberts N.D., Potter N.E., Heuser M., Thol F., Bolli N., 2016 Genomic Classification and Prognosis in Acute Myeloid Leukemia. N. Engl. J. Med. 374: 2209– 2221. 10.1056/NEJMoa1516192 27276561 PMC4979995 · DOI · Paper page
  45. Paschka P., Du J., Schlenk R.F., Gaidzik V.I., Bullinger L., Corbacioglu A., Späth D., Kayser S., Schlegelberger B., Krauter J., 2013 Secondary genetic lesions in acute myeloid leukemia with inv(16) or t(16;16): a study of the German-Austrian AML Study Group (AMLSG). Blood. 121: 170– 177. 10.1182/blood-2012-05-431486 23115274 · DOI
  46. Passegué E., Jamieson C.H., Ailles L.E., and Weissman I.L. 2003 Normal and leukemic hematopoiesis: are leukemias a stem cell disorder or a reacquisition of stem cell characteristics? Proc. Natl. Acad. Sci. USA. 100(Suppl 1): 11842– 11849. 10.1073/pnas.2034201100 14504387 PMC304096 · DOI
  47. Pietras E.M. 2017 Inflammation: a key regulator of hematopoietic stem cell fate in health and disease. Blood. 130: 1693– 1698. 10.1182/blood-2017-06-780882 28874349 PMC5639485 · DOI · Paper page
  48. Pietras E.M., Mirantes-Barbeito C., Fong S., Loeffler D., Kovtonyuk L.V., Zhang S., Lakshminarasimhan R., Chin C.P., Techner J.M., Will B., 2016 Chronic interleukin-1 exposure drives haematopoietic stem cells towards precocious myeloid differentiation at the expense of self-renewal. Nat. Cell Biol. 18: 607– 618. 10.1038/ncb3346 27111842 PMC4884136 · DOI · Paper page
  49. Rankin A.L., Mumm J.B., Murphy E., Turner S., Yu N., McClanahan T.K., Bourne P.A., Pierce R.H., Kastelein R., and Pflanz S. 2010 IL-33 induces IL-13-dependent cutaneous fibrosis. J. Immunol. 184: 1526– 1535. 10.4049/jimmunol.0903306 20042577 · DOI
  50. Reilly J.T. 2002 Class III receptor tyrosine kinases: role in leukaemogenesis. Br. J. Haematol. 116: 744– 757. 10.1046/j.0007-1048.2001.03294.x 11886377 · DOI
  51. Rhyasen G.W., and Starczynowski D.T. 2015 IRAK signalling in cancer. Br. J. Cancer. 112: 232– 237. 10.1038/bjc.2014.513 25290089 PMC4453441 · DOI
  52. Rhyasen G.W., Bolanos L., Fang J., Jerez A., Wunderlich M., Rigolino C., Mathews L., Ferrer M., Southall N., Guha R., 2013 Targeting IRAK1 as a therapeutic approach for myelodysplastic syndrome. Cancer Cell. 24: 90– 104. 10.1016/j.ccr.2013.05.006 23845443 PMC3711103 · DOI · Paper page
  53. Sadovnik I., Herrmann H., Eisenwort G., Blatt K., Hoermann G., Mueller N., Sperr W.R., and Valent P. 2017 Expression of CD25 on leukemic stem cells in BCR-ABL1+ CML: Potential diagnostic value and functional implications. Exp. Hematol. 51: 17– 24. 10.1016/j.exphem.2017.04.003 28457753 PMC6044418 · DOI
  54. Saito Y., Kitamura H., Hijikata A., Tomizawa-Murasawa M., Tanaka S., Takagi S., Uchida N., Suzuki N., Sone A., Najima Y., 2010 Identification of therapeutic targets for quiescent, chemotherapy-resistant human leukemia stem cells. Sci. Transl. Med. 2: 17ra9 10.1126/scitranslmed.3000349 PMC3005290 20371479 · DOI
  55. Sarry J.E., Murphy K., Perry R., Sanchez P.V., Secreto A., Keefer C., Swider C.R., Strzelecki A.C., Cavelier C., Récher C., 2011 Human acute myelogenous leukemia stem cells are rare and heterogeneous when assayed in NOD/SCID/IL2Rγc-deficient mice. J. Clin. Invest. 121: 384– 395. 10.1172/JCI41495 21157036 PMC3007135 · DOI
  56. Scheijen B., and Griffin J.D. 2002 Tyrosine kinase oncogenes in normal hematopoiesis and hematological disease. Oncogene. 21: 3314– 3333. 10.1038/sj.onc.1205317 12032772 · DOI
  57. Schneider C.A., Rasband W.S., and Eliceiri K.W. 2012 NIH Image to ImageJ: 25 years of image analysis. Nat. Methods. 9: 671– 675. 10.1038/nmeth.2089 22930834 PMC5554542 · DOI · Paper page
  58. Shastri A., Will B., Steidl U., and Verma A. 2017 Stem and progenitor cell alterations in myelodysplastic syndromes. Blood. 129: 1586– 1594. 10.1182/blood-2016-10-696062 28159737 PMC5364336 · DOI
  59. Stirewalt D.L., and Radich J.P. 2003 The role of FLT3 in haematopoietic malignancies. Nat. Rev. Cancer. 3: 650– 665. 10.1038/nrc1169 12951584 · DOI · Paper page
  60. Towne J.E., Garka K.E., Renshaw B.R., Virca G.D., and Sims J.E. 2004 Interleukin (IL)-1F6, IL-1F8, and IL-1F9 signal through IL-1Rrp2 and IL-1RAcP to activate the pathway leading to NF-kappaB and MAPKs. J. Biol. Chem. 279: 13677– 13688. 10.1074/jbc.M400117200 14734551 · DOI
  61. Warr M.R., Pietras E.M., and Passegué E. 2011 Mechanisms controlling hematopoietic stem cell functions during normal hematopoiesis and hematological malignancies. Wiley Interdiscip. Rev. Syst. Biol. Med. 3: 681– 701. 10.1002/wsbm.145 21412991 · DOI · Paper page
  62. Weber A., Wasiliew P., and Kracht M. 2010 Interleukin-1 (IL-1) pathway. Sci. Signal. 3: cm1. 20086235
  63. Yasuda T., Ueno T., Fukumura K., Yamato A., Ando M., Yamaguchi H., Soda M., Kawazu M., Sai E., Yamashita Y., 2014 Leukemic evolution of donor-derived cells harboring IDH2 and DNMT3A mutations after allogeneic stem cell transplantation. Leukemia. 28: 426– 428. 10.1038/leu.2013.278 24067491 · DOI
  64. Zhang B., Chu S., Agarwal P., Campbell V.L., Hopcroft L., Jørgensen H.G., Lin A., Gaal K., Holyoake T.L., and Bhatia R. 2016 Inhibition of interleukin-1 signaling enhances elimination of tyrosine kinase inhibitor-treated CML stem cells. Blood. 128: 2671– 2682. 10.1182/blood-2015-11-679928 27621307 PMC5146743 · DOI
  65. Zhao K., Yin L.L., Zhao D.M., Pan B., Chen W., Cao J., Cheng H., Li Z.Y., Li D.P., Sang W., 2014 IL1RAP as a surface marker for leukemia stem cells is related to clinical phase of chronic myeloid leukemia patients. Int. J. Clin. Exp. Med. 7: 4787– 4798. 25663975 PMC4307422
  66. Zheng R., Bailey E., Nguyen B., Yang X., Piloto O., Levis M., and Small D. 2011 Further activation of FLT3 mutants by FLT3 ligand. Oncogene. 30: 4004– 4014. 10.1038/onc.2011.110 21516120 PMC3155740 · DOI

Cited by

Sorted by citations

Authors
Mitchell, K., Barreyro, L., Todorova, T. I., Taylor, S. J., Antony-Debré, I., Narayanagari, S.-R., Carvajal, L. A., Leite, J., Piperdi, Z., Pendurti, G., Mantzaris, I., Paietta, E., Verma, A., Gritsman, K., & Steidl, U.
Affiliations
  • Albert Einstein College of Medicine (US)
  • Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 1
Corresponding author
Steidl, Ulrich
ORCID
Venue
Journal of Experimental Medicine
Publisher
Rockefeller University Press
Published
2018-05-17
Volume
215
Issue
6
Pages
1709-1727
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
DOI
10.1084/jem.20180147
PMC
PMC5987926
OpenAlex
W2803596986
Cited by
97
References
5
Citations by year
2026: 7 · 2025: 12 · 2024: 15 · 2023: 8 · 2022: 17 · 2021: 16 · 2020: 13 · 2019: 7 · 2018: 2
FWCI
6.81
Type
journal article
Language
en
Open access
Licence
Locations
  • The Journal of Experimental Medicine (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
Funders
  • New York State Stem Cell Science (C029154, C30292GG)
  • National Institutes of Health (R01CA166429, R01CA196973, U10CA180827, T32 GM007491)
Topics
  • Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
  • Health Sciences › Medicine › Pharmacology › Flavonoids in Medical Research
Keywords
IL1RAP, acute myeloid leukemia, FLT3, CD117, receptor tyrosine kinase, oncogenic signaling, leukemogenesis, hematopoietic stem cells, protein-protein interaction
MeSH terms
Adult, Aged, Animals, Antibodies, Cell Differentiation, Female, Hematopoiesis, Humans, Male, Membrane Proteins, Middle Aged, Models, Biological, Protein Binding, Signal Transduction, Leukemia, Myeloid, Acute, Down-Regulation, Apoptosis, Gene Deletion, Proto-Oncogene Proteins c-kit, Stem Cell Factor, Cell Line, Tumor, Cell Proliferation, Mice, Interleukin-1 Receptor Accessory Protein, Carcinogenesis

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