{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T12:36:11Z","timestamp":1792067771095,"version":"4.4.0"},"reference-count":80,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"800","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Signal."],"published-print":{"date-parts":[[2023,8,29]]},"abstract":"<jats:p>\n            Cell stemness is characterized by quiescence, pluripotency, and long-term self-renewal capacity. Therapy-resistant leukemic stem cells (LSCs) are the primary cause of relapse in patients with chronic and acute myeloid leukemia (CML and AML). However, the same signaling pathways frequently support stemness in both LSCs and normal hematopoietic stem cells (HSCs), making LSCs difficult to therapeutically target. In cell lines and patient samples, we found that interleukin-33 (IL-33) signaling promoted stemness only in leukemia cells in a subtype-specific manner. The IL-33 receptor ST2 was abundant on the surfaces of CD34\n            <jats:sup>+<\/jats:sup>\n            <jats:italic>BCR\/ABL1<\/jats:italic>\n            CML and CD34\n            <jats:sup>+<\/jats:sup>\n            AML cells harboring\n            <jats:italic>AML1\/ETO<\/jats:italic>\n            and\n            <jats:italic>DEK\/NUP214<\/jats:italic>\n            translocations or deletion of chromosome 9q [del(9q)]. The cell surface abundance of ST2, which was lower or absent on other leukemia subtypes and HSCs, correlated with stemness, activated Wnt signaling, and repressed Notch signaling. IL-33\u2013ST2 signaling promoted the maintenance and expansion of AML1\/ETO\u2013, DEK\/NUP214\u2013, and BCR\/ABL1\u2013positive LSCs in culture and in mice by activating Wnt, MAPK, and NF-\u03baB signaling. Wnt signaling and its inhibition of the Notch pathway up-regulated the expression of the gene encoding ST2, thus forming a cell-autonomous loop. IL-33\u2013ST2 signaling promoted the resistance of CML cells to the tyrosine kinase inhibitor (TKI) nilotinib and of AML cells to standard chemotherapy. Thus, inhibiting IL-33\u2013ST2 signaling may target LSCs to overcome resistance to chemotherapy or TKIs in these subtypes of leukemia.\n          <\/jats:p>","DOI":"10.1126\/scisignal.add7705","type":"journal-article","created":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T17:59:02Z","timestamp":1693331942000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":20,"title":["IL-33\u2013ST2 signaling promotes stemness in subtypes of myeloid leukemia cells through the Wnt and Notch pathways"],"prefix":"10.1126","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9579-3805","authenticated-orcid":true,"given":"Pascal","family":"Naef","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern 3010, Switzerland."},{"name":"Tumor Immunology, Department for BioMedical Research (DBMR), University of Bern, Bern 3008, Switzerland."},{"name":"Graduate School of Cellular and Biomedical Sciences, University of Bern, Bern 3012, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5632-7833","authenticated-orcid":true,"given":"Ramin","family":"Radpour","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern 3010, Switzerland."},{"name":"Tumor Immunology, Department for BioMedical Research (DBMR), University of Bern, Bern 3008, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1685-2078","authenticated-orcid":true,"given":"Carla A.","family":"Jaeger-Ruckstuhl","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern 3010, Switzerland."},{"name":"Tumor Immunology, Department for BioMedical Research (DBMR), University of Bern, Bern 3008, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nils","family":"Bodmer","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern 3010, Switzerland."},{"name":"Tumor Immunology, Department for BioMedical Research (DBMR), University of Bern, Bern 3008, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9771-746X","authenticated-orcid":true,"given":"Gabriela M.","family":"Baerlocher","sequence":"additional","affiliation":[{"name":"Laboratory for Hematopoiesis and Molecular Genetics, Experimental Hematology, Department of BioMedical Research (DBMR), University of Bern, Bern 3008, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2116-5536","authenticated-orcid":true,"given":"Hartmut","family":"Doehner","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, University Hospital of Ulm, Ulm 89081, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstanze","family":"Doehner","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, University Hospital of Ulm, Ulm 89081, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7512-513X","authenticated-orcid":true,"given":"Carsten","family":"Riether","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern 3010, Switzerland."},{"name":"Tumor Immunology, Department for BioMedical Research (DBMR), University of Bern, Bern 3008, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1773-5436","authenticated-orcid":true,"given":"Adrian F.","family":"Ochsenbein","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern 3010, Switzerland."},{"name":"Tumor Immunology, Department for BioMedical Research (DBMR), University of Bern, Bern 3008, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2014.89"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)69780-8"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-12-86"},{"key":"e_1_3_2_5_2","first-page":"485","article-title":"Cytosine arabinoside (NSC-63878) and daunorubicin (NSC-83142) therapy in acute nonlymphocytic leukemia","volume":"57","author":"Yates J. 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