{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:55:35Z","timestamp":1789016135554,"version":"build-2803163510"},"reference-count":35,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"vor","delay-in-days":549,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","exphem.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Experimental Hematology"],"published-print":{"date-parts":[[2021,5]]},"DOI":"10.1016\/j.exphem.2021.02.008","type":"journal-article","created":{"date-parts":[[2021,2,21]],"date-time":"2021-02-21T00:32:06Z","timestamp":1613867526000},"page":"57-65.e5","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":8,"special_numbering":"C","title":["The delta isoform of phosphatidylinositol-3-kinase predominates in chronic myelomonocytic leukemia and can be targeted effectively with umbralisib and ruxolitinib"],"prefix":"10.1016","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0857-9542","authenticated-orcid":false,"given":"Matthew T.","family":"Villaume","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Pia","family":"Arrate","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haley E.","family":"Ramsey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn I.","family":"Sunthankar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4884-3926","authenticated-orcid":false,"given":"Matthew T.","family":"Jenkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara K.","family":"Moyo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6905-9196","authenticated-orcid":false,"given":"Brianna N.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2664-3541","authenticated-orcid":false,"given":"Melissa A.","family":"Fischer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0854-784X","authenticated-orcid":false,"given":"Merrida A.","family":"Childress","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka E.","family":"Gorska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1140-9154","authenticated-orcid":false,"given":"P. Brent","family":"Ferrell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Savona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.exphem.2021.02.008_bib0001","doi-asserted-by":"crossref","first-page":"2428","DOI":"10.1200\/JCO.2012.47.3314","article-title":"Prognostic score including gene mutations in chronic myelomonocytic leukemia","volume":"31","author":"Itzykson","year":"2013","journal-title":"J Clin Oncol"},{"key":"10.1016\/j.exphem.2021.02.008_bib0002","doi-asserted-by":"crossref","first-page":"5068","DOI":"10.1182\/blood-2012-10-460170","article-title":"GM-CSF-dependent pSTAT5 sensitivity is a feature with therapeutic potential in chronic myelomonocytic leukemia","volume":"121","author":"Padron","year":"2013","journal-title":"Blood"},{"key":"10.1016\/j.exphem.2021.02.008_bib0003","doi-asserted-by":"crossref","first-page":"3746","DOI":"10.1158\/1078-0432.CCR-15-2781","article-title":"A multi-institution phase I trial of ruxolitinib in patients with chronic myelomonocytic leukemia (CMML)","volume":"22","author":"Padron","year":"2016","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.exphem.2021.02.008_bib0004","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1084\/jem.184.4.1377","article-title":"Interleukin 10 inhibits growth and granulocyte\/macrophage colony-stimulating factor production in chronic myelomonocytic leukemia cells","volume":"184","author":"Geissler","year":"1996","journal-title":"J Exp Med"},{"key":"10.1016\/j.exphem.2021.02.008_bib0005","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1016\/j.ccr.2012.10.023","article-title":"JAK2\/STAT5 inhibition circumvents resistance to PI3K\/mTOR blockade: a rationale for cotargeting these pathways in metastatic breast cancer","volume":"22","author":"Britschgi","year":"2012","journal-title":"Cancer Cell"},{"key":"10.1016\/j.exphem.2021.02.008_bib0006","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1111\/jcmm.12162","article-title":"Co-targeting the PI3K\/mTOR and JAK2 signalling pathways produces synergistic activity against myeloproliferative neoplasms","volume":"17","author":"Bartalucci","year":"2013","journal-title":"J Cell Mol Med"},{"key":"10.1016\/j.exphem.2021.02.008_bib0007","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1111\/jcmm.12156","article-title":"Combination treatment for myeloproliferative neoplasms using JAK and pan-class I PI3K inhibitors","volume":"17","author":"Choong","year":"2013","journal-title":"J Cell Mol Med"},{"key":"10.1016\/j.exphem.2021.02.008_bib0008","doi-asserted-by":"crossref","first-page":"E7554","DOI":"10.1073\/pnas.1703094114","article-title":"Molecularly targeted drug combinations demonstrate selective effectiveness for myeloid- and lymphoid-derived hematologic malignancies","volume":"114","author":"Kurtz","year":"2017","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.exphem.2021.02.008_bib0009","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/S1470-2045(18)30082-2","article-title":"Umbralisib, a novel PI3K\u03b4 and casein kinase-1\u03b5 inhibitor, in relapsed or refractory chronic lymphocytic leukaemia and lymphoma: an open-label, phase 1, dose-escalation, first-in-human study","volume":"19","author":"Burris","year":"2018","journal-title":"Lancet Oncol"},{"key":"10.1016\/j.exphem.2021.02.008_bib0010","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1182\/blood-2004-08-3225","article-title":"Essential role for the p110\u03b4 isoform in phosphoinositide 3-kinase activation and cell proliferation in acute myeloid leukemia","volume":"106","author":"Sujobert","year":"2005","journal-title":"Blood"},{"key":"10.1016\/j.exphem.2021.02.008_bib0011","doi-asserted-by":"crossref","first-page":"6648","DOI":"10.1038\/sj.onc.1209670","article-title":"A selective inhibitor of the p110\u03b4 isoform of PI 3-kinase inhibits AML cell proliferation and survival and increases the cytotoxic effects of VP16","volume":"25","author":"Billottet","year":"2006","journal-title":"Oncogene"},{"key":"10.1016\/j.exphem.2021.02.008_bib0012","first-page":"19","article-title":"Resurrecting response to ruxolitinib: a phase I study testing the combination of ruxolitinib and the PI3K delta inhibitor umbralisib in ruxolitinib-experienced myelofibrosis","volume":"2","author":"Moyo","year":"2018","journal-title":"Hemasphere"},{"key":"10.1016\/j.exphem.2021.02.008_bib0013","doi-asserted-by":"crossref","first-page":"2466","DOI":"10.1158\/0008-5472.CAN-18-2970","article-title":"HEMap: an interactive online resource for characterizing molecular phenotypes across hematologic malignancies","volume":"79","author":"P\u00f6l\u00f6nen","year":"2019","journal-title":"Cancer Res"},{"key":"10.1016\/j.exphem.2021.02.008_bib0014","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/nature11003","article-title":"The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity","volume":"483","author":"Barretina","year":"2012","journal-title":"Nature"},{"key":"10.1016\/j.exphem.2021.02.008_bib0015","doi-asserted-by":"crossref","first-page":"W147","DOI":"10.1093\/nar\/gkw419","article-title":"Heatmapper: web-enabled heat mapping for all","volume":"44","author":"Babicki","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"10.1016\/j.exphem.2021.02.008_bib0016","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.csbj.2015.09.001","article-title":"Searching for drug synergy in complex dose\u2013response landscapes using an interaction potency model","volume":"13","author":"Yadav","year":"2015","journal-title":"Comput Struct Biotechnol J"},{"key":"10.1016\/j.exphem.2021.02.008_bib0017","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1038\/nrc1804","article-title":"Mapping normal and cancer cell signalling networks: towards single-cell proteomics","volume":"6","author":"Irish","year":"2006","journal-title":"Nat Rev Cancer"},{"key":"10.1016\/j.exphem.2021.02.008_bib0018","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-017-02470-8","article-title":"Discovery of human cell selective effector molecules using single cell multiplexed activity metabolomics","volume":"9","author":"Earl","year":"2018","journal-title":"Nat Commun"},{"key":"10.1016\/j.exphem.2021.02.008_bib0019","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/nmeth872","article-title":"Fluorescent cell barcoding in flow cytometry allows high-throughput drug screening and signaling profiling","volume":"3","author":"Krutzik","year":"2006","journal-title":"Nat Methods"},{"key":"10.1016\/j.exphem.2021.02.008_bib0020","doi-asserted-by":"crossref","first-page":"e5145","DOI":"10.1371\/journal.pone.0005145","article-title":"Regulation of p110\u03b4 PI 3-kinase gene expression","volume":"4","author":"Kok","year":"2009","journal-title":"PLoS One"},{"key":"10.1016\/j.exphem.2021.02.008_bib0021","doi-asserted-by":"crossref","first-page":"2359","DOI":"10.1038\/sj.leu.2404805","article-title":"Gene expression profiling separates chronic myelomonocytic leukemia in two molecular subtypes","volume":"21","author":"Gelsi-Boyer","year":"2007","journal-title":"Leukemia"},{"key":"10.1016\/j.exphem.2021.02.008_bib0022","doi-asserted-by":"crossref","first-page":"2274","DOI":"10.1182\/blood-2012-10-460832","article-title":"P110a-mediated constitutive PI3K signaling limits the efficacy of p110d-selective inhibition in mantle cell lymphoma, particularly with multiple relapse","volume":"121","author":"Iyengar","year":"2013","journal-title":"Blood"},{"key":"10.1016\/j.exphem.2021.02.008_bib0023","doi-asserted-by":"crossref","first-page":"2402","DOI":"10.1038\/leu.2016.224","article-title":"The novel PI3K-\u03b4 inhibitor TGR-1202 enhances brentuximab vedotin-induced Hodgkin lymphoma cell death via mitotic arrest","volume":"30","author":"Locatelli","year":"2016","journal-title":"Leukemia"},{"key":"10.1016\/j.exphem.2021.02.008_bib0024","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1182\/blood-2016-08-731240","article-title":"Silencing c-Myc translation as a therapeutic strategy through targeting PI3K\u03b4 and CK1\u03b5 in hematological malignancies","volume":"129","author":"Deng","year":"2017","journal-title":"Blood"},{"key":"10.1016\/j.exphem.2021.02.008_bib0025","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1007\/s11899-017-0408-8","article-title":"Therapy for chronic myelomonocytic leukemia in a new era","volume":"12","author":"Moyo","year":"2017","journal-title":"Curr Hematol Malig Rep"},{"key":"10.1016\/j.exphem.2021.02.008_bib0026","doi-asserted-by":"crossref","first-page":"10767","DOI":"10.1038\/ncomms10767","article-title":"Mutation allele burden remains unchanged in chronic myelomonocytic leukaemia responding to hypomethylating agents","volume":"7","author":"Merlevede","year":"2016","journal-title":"Nat Commun"},{"key":"10.1016\/j.exphem.2021.02.008_bib0027","doi-asserted-by":"crossref","DOI":"10.1016\/j.ebiom.2020.102904","article-title":"Chronic myelomonocytic leukaemia stem cell transcriptomes anticipate disease morphology and outcome","volume":"58","author":"Wiseman","year":"2020","journal-title":"EBioMedicine"},{"key":"10.1016\/j.exphem.2021.02.008_bib0028","doi-asserted-by":"crossref","first-page":"20065","DOI":"10.1074\/jbc.R700003200","article-title":"The interferon regulatory factor family in host defense: mechanism of action","volume":"282","author":"Ozato","year":"2007","journal-title":"J Biol Chem"},{"key":"10.1016\/j.exphem.2021.02.008_bib0029","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/0167-5699(94)90007-8","article-title":"NF-ATp: a transcription factor required for the co-ordinate induction of several cytokine genes","volume":"15","author":"Rao","year":"1994","journal-title":"Immunol Today"},{"key":"10.1016\/j.exphem.2021.02.008_bib0030","doi-asserted-by":"crossref","first-page":"5991","DOI":"10.1182\/blood-2010-04-281527","article-title":"Endogenous oncogenic NRAS mutation promotes aberrant GM-CSF signaling in granulocytic\/monocytic precursors in a murine model of chronic myelomonocytic leukemia","volume":"116","author":"Wang","year":"2010","journal-title":"Blood"},{"key":"10.1016\/j.exphem.2021.02.008_bib0031","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1172\/JCI98785","article-title":"Targeting compensatory MEK\/ERK activation increases JAK inhibitor efficacy in myeloproliferative neoplasms","volume":"129","author":"Stivala","year":"2019","journal-title":"J Clin Invest"},{"key":"10.1016\/j.exphem.2021.02.008_bib0032","doi-asserted-by":"crossref","first-page":"e24574","DOI":"10.4161\/jkst.24574","article-title":"JAK2-V617F-induced MAPK activity is regulated by PI3K and acts synergistically with PI3K on the proliferation of JAK2-V617F-positive cells","volume":"2","author":"Wolf","year":"2013","journal-title":"JAK-STAT"},{"key":"10.1016\/j.exphem.2021.02.008_bib0033","doi-asserted-by":"crossref","first-page":"2838","DOI":"10.1182\/blood-2013-10-535104","article-title":"PI3K p110\u03b4 uniquely promotes gain-of-function Shp2-induced GM-CSF hypersensitivity in a model of JMML","volume":"123","author":"Goodwin","year":"2014","journal-title":"Blood"},{"key":"10.1016\/j.exphem.2021.02.008_bib0034","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.4049\/jimmunol.1701703","article-title":"The PI3K p110\u03b4 isoform inhibitor idelalisib preferentially inhibits human regulatory T cell function","volume":"202","author":"Chellappa","year":"2019","journal-title":"J Immunol"},{"key":"10.1016\/j.exphem.2021.02.008_bib0035","doi-asserted-by":"crossref","first-page":"3072","DOI":"10.1182\/bloodadvances.2020001800","article-title":"The dual PI3K\u03b4\/CK1\u03b5 inhibitor umbralisib exhibits unique immunomodulatory effects on CLL T cells","volume":"4","author":"Maharaj","year":"2020","journal-title":"Blood Adv"}],"container-title":["Experimental Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0301472X21000898?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0301472X21000898?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,4]],"date-time":"2025-10-04T08:35:34Z","timestamp":1759566934000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0301472X21000898"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5]]},"references-count":35,"alternative-id":["S0301472X21000898"],"URL":"https:\/\/doi.org\/10.1016\/j.exphem.2021.02.008","relation":{},"ISSN":["0301-472X"],"issn-type":[{"value":"0301-472X","type":"print"}],"subject":[],"published":{"date-parts":[[2021,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"The delta isoform of phosphatidylinositol-3-kinase predominates in chronic myelomonocytic leukemia and can be targeted effectively with umbralisib and ruxolitinib","name":"articletitle","label":"Article Title"},{"value":"Experimental Hematology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.exphem.2021.02.008","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Published by Elsevier Inc. on behalf of ISEH -- Society for Hematology and Stem Cells.","name":"copyright","label":"Copyright"}]}}