{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T21:46:23Z","timestamp":1773697583400,"version":"3.50.1"},"reference-count":50,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2021,7,24]],"date-time":"2021-07-24T00:00:00Z","timestamp":1627084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["21771"],"award-info":[{"award-number":["21771"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Associazione Italiana Contro le Leucemie-Linfomi e Mieloma","award":["AIL-TV"],"award-info":[{"award-number":["AIL-TV"]}]},{"DOI":"10.13039\/501100004710","name":"Fondazione Umberto Veronesi","doi-asserted-by":"publisher","award":["2064"],"award-info":[{"award-number":["2064"]}],"id":[{"id":"10.13039\/501100004710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007479","name":"Fondazione Cassa di Risparmio di Padova e Rovigo","doi-asserted-by":"publisher","award":["17\/07_1FCR"],"award-info":[{"award-number":["17\/07_1FCR"]}],"id":[{"id":"10.13039\/100007479","id-type":"DOI","asserted-by":"publisher"}]},{"name":"progetti di rilevante interesse nazionale","award":["20178S4EK9"],"award-info":[{"award-number":["20178S4EK9"]}]},{"name":"Fondazione Citt\u00e0 della Speranza Istituto di Ricerca Pediatrica","award":["19\/08"],"award-info":[{"award-number":["19\/08"]}]},{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la ricerca sul cancro","doi-asserted-by":"publisher","award":["19186"],"award-info":[{"award-number":["19186"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Lymphoblastic lymphoma (LBL) is the second most common type of non-Hodgkin lymphoma in childhood, mainly of T cell origin (T-LBL). Although current treatment protocols allow a complete remission in 85% of cases, the second-line treatment overall survival for patients with progressive or relapsed disease is around 14%, making this the major issue to be confronted. Thus, we performed a Reverse Phase Protein Array study in a cohort of 22 T-LBL patients to find reliable disease risk marker(s) and new therapeutic targets to improve pediatric T-LBL patients\u2019 outcome. Interestingly, we pinpointed JAK2 Y1007-1008 as a potential prognosis marker as well as a therapeutic target in poor prognosis patients. Hence, the hyperactivation of the JAK1\/2-STAT6 pathway characterizes these latter patients. Moreover, we functionally demonstrated that STAT6 hyperactivation contributes to therapy resistance by binding the glucocorticoid receptor, thus inhibiting its transcriptional activity. This was further confirmed by specific STAT6 gene silencing followed by dexamethasone treatment. Finally, JAK1\/2-STAT6 pathway inhibition by ruxolitinib, an FDA approved drug, in cell line models and in one T-LBL primary sample led to cell proliferation reduction and increased apoptosis. Globally, our results identify a new potential prognostic marker and suggest a novel therapeutic approach to overcome therapy resistance in pediatric T-LBL patients.<\/jats:p>","DOI":"10.3390\/cancers13153724","type":"journal-article","created":{"date-parts":[[2021,7,25]],"date-time":"2021-07-25T22:06:21Z","timestamp":1627250781000},"page":"3724","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Ruxolitinib as a Novel Therapeutic Option for Poor Prognosis T-LBL Pediatric Patients"],"prefix":"10.3390","volume":"13","author":[{"given":"Giulia","family":"Veltri","sequence":"first","affiliation":[{"name":"Maternal and Child Health Department, Division of Pediatric Hematology, Oncology and Stem Cell Transplant, University of Padova, 35128 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Silvestri","sequence":"additional","affiliation":[{"name":"Maternal and Child Health Department, Division of Pediatric Hematology, Oncology and Stem Cell Transplant, University of Padova, 35128 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilaria","family":"Gallingani","sequence":"additional","affiliation":[{"name":"Maternal and Child Health Department, Division of Pediatric Hematology, Oncology and Stem Cell Transplant, University of Padova, 35128 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Max","family":"Sandei","sequence":"additional","affiliation":[{"name":"Fondazione Citt\u00e0 della Speranza Istituto di Ricerca Pediatrica, Oncohematology, Stem Cell Transplant and Gene Therapy Research Area, 35122 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Vencato","sequence":"additional","affiliation":[{"name":"Fondazione Citt\u00e0 della Speranza Istituto di Ricerca Pediatrica, Oncohematology, Stem Cell Transplant and Gene Therapy Research Area, 35122 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"Lovisa","sequence":"additional","affiliation":[{"name":"Maternal and Child Health Department, Division of Pediatric Hematology, Oncology and Stem Cell Transplant, University of Padova, 35128 Padova, Italy"},{"name":"Fondazione Citt\u00e0 della Speranza Istituto di Ricerca Pediatrica, Oncohematology, Stem Cell Transplant and Gene Therapy Research Area, 35122 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuliana","family":"Cortese","sequence":"additional","affiliation":[{"name":"Department of Statistical Sciences, University of Padova, 35121 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Pillon","sequence":"additional","affiliation":[{"name":"Clinic of Pediatric Oncohematology, University of Padova, 35128 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisa","family":"Carraro","sequence":"additional","affiliation":[{"name":"Clinic of Pediatric Oncohematology, University of Padova, 35128 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Bresolin","sequence":"additional","affiliation":[{"name":"Maternal and Child Health Department, Division of Pediatric Hematology, Oncology and Stem Cell Transplant, University of Padova, 35128 Padova, Italy"},{"name":"Fondazione Citt\u00e0 della Speranza Istituto di Ricerca Pediatrica, Oncohematology, Stem Cell Transplant and Gene Therapy Research Area, 35122 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Biffi","sequence":"additional","affiliation":[{"name":"Maternal and Child Health Department, Division of Pediatric Hematology, Oncology and Stem Cell Transplant, University of Padova, 35128 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Basso","sequence":"additional","affiliation":[{"name":"Maternal and Child Health Department, Division of Pediatric Hematology, Oncology and Stem Cell Transplant, University of Padova, 35128 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2359-1056","authenticated-orcid":false,"given":"Benedetta","family":"Accordi","sequence":"additional","affiliation":[{"name":"Maternal and Child Health Department, Division of Pediatric Hematology, Oncology and Stem Cell Transplant, University of Padova, 35128 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4802-1866","authenticated-orcid":false,"given":"Lara","family":"Mussolin","sequence":"additional","affiliation":[{"name":"Maternal and Child Health Department, Division of Pediatric Hematology, Oncology and Stem Cell Transplant, University of Padova, 35128 Padova, Italy"},{"name":"Fondazione Citt\u00e0 della Speranza Istituto di Ricerca Pediatrica, Oncohematology, Stem Cell Transplant and Gene Therapy Research Area, 35122 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6283-7728","authenticated-orcid":false,"given":"Valentina","family":"Serafin","sequence":"additional","affiliation":[{"name":"Maternal and Child Health Department, Division of Pediatric Hematology, Oncology and Stem Cell Transplant, University of Padova, 35128 Padova, Italy"},{"name":"Fondazione Citt\u00e0 della Speranza Istituto di Ricerca Pediatrica, Oncohematology, Stem Cell Transplant and Gene Therapy Research Area, 35122 Padova, 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J. Haematol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"454\u2013461","DOI":"10.1111\/bjh.12042","article-title":"The immunophenotype of T-lymphoblastic lymphoma in children and adolescents: A Children\u2019s Oncology Group report","volume":"159","author":"Patel","year":"2012","journal-title":"Br. J. Haematol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1200\/JCO.1995.13.2.359","article-title":"Non-Hodgkin\u2019s lymphomas of childhood and adolescence: Results of a treatment stratified for biologic subtypes and stage--a report of the Berlin-Frankfurt-M\u00fcnster Group","volume":"13","author":"Reiter","year":"1995","journal-title":"J. Clin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1182\/blood-2010-06-292615","article-title":"Effectiveness of high-dose methotrexate in T-cell lymphoblastic leukemia and advanced-stage lymphoblastic lymphoma: A randomized study by the Children\u2019s Oncology Group (POG 9404)","volume":"118","author":"Asselin","year":"2011","journal-title":"Blood"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1002\/pbc.22162","article-title":"Long-term results of AIEO P LNH\u201392 protocol for the treatment of pediatric lymphoblastic lymphoma: A report of the Italian Association of Pediatric Hematology and Oncology","volume":"53","author":"Pillon","year":"2009","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3363","DOI":"10.1200\/JCO.2008.19.3367","article-title":"Poor outcome for children and adolescents with progressive disease or relapse of lymphoblastic lymphoma: A report from the berlin-frankfurt-muenster group","volume":"27","author":"Burkhardt","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3643","DOI":"10.1021\/acs.jproteome.6b00457","article-title":"Proteomic Alterations in Response to Hypoxia Inducible Factor 2\u03b1 in Normoxic Neuroblastoma Cells","volume":"15","author":"Cimmino","year":"2016","journal-title":"J. Proteome Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"34449","DOI":"10.1038\/srep34449","article-title":"Deciphering KRAS and NRAS mutated clone dynamics in MLL-AF4 paediatric leukaemia by ultra deep sequencing analysis","volume":"6","author":"Trentin","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"88","DOI":"10.3109\/08977194.2012.660936","article-title":"Biology and significance of the JAK\/STAT signalling pathways","volume":"30","author":"Kiu","year":"2012","journal-title":"Growth Factors"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1182\/blood.V99.2.618","article-title":"Signal transducer andactivator of transcription 6 is frequently activated in Hodgkin and Reed\u2013Sternberg cells of Hodgkin lymphoma","volume":"99","author":"Skinnider","year":"2002","journal-title":"Blood"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1182\/blood-2003-10-3545","article-title":"Constitutive STAT6 activation in primary mediastinal large B-cell lymphoma","volume":"104","author":"Guiter","year":"2004","journal-title":"Blood"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1046\/j.0022-202x.2001.01436.x","article-title":"Constitutive and interleukin-7- and interleukin-15-stimulated DNA binding of STAT and novel factors in cutaneous T cell lymphoma cells","volume":"117","author":"Qin","year":"2001","journal-title":"J. Invest. Dermatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"13897","DOI":"10.1073\/pnas.94.25.13897","article-title":"Proliferation of adult T cell leukemia\/lymphoma cells is associated with the constitutive activation of JAK\/STAT proteins","volume":"94","author":"Takemoto","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2535","DOI":"10.1182\/blood-2004-09-3701","article-title":"Biallelic mutation of SOCS-1 impairs JAK2 degradation and sustains phopho-JAK2 action in the MedB-1 mediastinal lymphoma line","volume":"105","author":"Melzner","year":"2005","journal-title":"Blood"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3008","DOI":"10.1158\/1078-0432.CCR-11-3145","article-title":"Ruxolitinib: The first FDA approved therapy for the treatment of myelofibrosis","volume":"18","author":"Mascarenhas","year":"2012","journal-title":"Clin Cancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1038\/bmt.2017.120","article-title":"Regional intra-arterial steroid treatment in 120 patients with steroid-resistant or -dependent GvHD","volume":"52","author":"Shapira","year":"2017","journal-title":"Bone Marrow Transplant."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e427","DOI":"10.3324\/haematol.2018.192088","article-title":"Clinical efficacy of ruxolitinib and chemotherapy in a child with Philadelphia chromosome-like acute lymphoblastic leukemia with GOLGA5-JAK2 fusion and induction failure","volume":"103","author":"Ding","year":"2018","journal-title":"Haematologica"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1093\/bioinformatics\/btg382","article-title":"A global test for groups of genes: Testing association with a clinical outcome","volume":"20","author":"Goeman","year":"2004","journal-title":"Bioinformatics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1996","DOI":"10.1128\/MCB.18.4.1996","article-title":"Stat proteins control lymphocyte proliferation by regulating p27Kip1 expression","volume":"18","author":"Kaplan","year":"1998","journal-title":"Mol. Cell Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1038\/leu.2014.134","article-title":"An aberrant microRNA signature in childhood T-cell lymphoblastic lymphoma affecting CDKN1B expression, NOTCH1 and growth factor signaling pathways","volume":"28","author":"Mussolin","year":"2014","journal-title":"Leukemia"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1146\/annurev.immunol.17.1.701","article-title":"The IL-4 receptor: Signaling mechanisms and biologic functions","volume":"17","author":"Nelms","year":"1999","journal-title":"Ann. Rev. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2750","DOI":"10.1182\/blood-2017-05-784603","article-title":"Glucocorticoid resistance is reverted by LCK inhibition in pediatric T-cell acute lymphoblastic leukemia","volume":"130","author":"Serafin","year":"2017","journal-title":"Blood"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/S0014-5793(00)02297-3","article-title":"The glucocorticoid receptor and STAT6 physically and functionally interact in T-lymphocytes","volume":"487","author":"Biola","year":"2000","journal-title":"FEBS Lett."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/S1074-7613(00)80398-2","article-title":"A new dexamethasone-induced gene of the leucine zipper family protects T lymphocytes from TCR\/CD3-activated cell death","volume":"7","author":"Zollo","year":"1997","journal-title":"Immunity"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1016\/j.bmc.2006.10.015","article-title":"Synthesis and evaluation of 2-{[2-(4-hydroxyphenyl)-ethyl]amino}pyrimidine-5-carboxamide derivatives as novel STAT6 inhibitors","volume":"15","author":"Nagashima","year":"2007","journal-title":"Bioorganic Med. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1111\/bjh.15793","article-title":"Lymphoblastic lymphoma in children and adolescents: Review of current challenges and future opportunities","volume":"185","author":"Burkhardt","year":"2019","journal-title":"Br. J. Haematol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3533","DOI":"10.1200\/JCO.2008.21.1318","article-title":"Minimal disseminated disease in childhood T-cell lymphoblastic lymphoma: A report from the children\u2019s oncology group","volume":"27","author":"Sandlund","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1906","DOI":"10.1002\/pbc.25607","article-title":"Detection and role of minimal disseminated disease in children with lymphoblastic lymphoma: The AIEOP experience","volume":"62","author":"Mussolin","year":"2015","journal-title":"Pediatr. Blood Cancer."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1200\/JCO.2011.39.7661","article-title":"Clinical impact of NOTCH1 and\/or FBXW7 mutations, FLASH deletion, and TCR status in pediatric T-cell lymphoblastic lymphoma","volume":"30","author":"Callens","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"107886","DOI":"10.18632\/oncotarget.22386","article-title":"Clinical impact of miR-223 expression in pediatric T-Cell lymphoblastic lymphoma","volume":"8","author":"Pomari","year":"2017","journal-title":"Oncotarget"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e1900091","DOI":"10.1002\/prca.201900091","article-title":"Utility of a Reverse Phase Protein Array to Evaluate Multiple Biomarkers in Diffuse Large B-Cell Lymphoma","volume":"14","author":"Suzuki","year":"2020","journal-title":"Proteom. Clin. Appl."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e17","DOI":"10.3324\/haematol.2018.199257","article-title":"Pre-clinical evaluation of second generation PIM inhibitors for the treatment of T-cell acute lymphoblastic leukemia and lymphoma","volume":"104","author":"Peirs","year":"2019","journal-title":"Haematologica"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1182\/blood.2019003880","article-title":"Targeting cytokine- and therapy-induced PIM1 activation in preclinical models of T-cell acute lymphoblastic leukemia and lymphoma","volume":"135","author":"Morscio","year":"2020","journal-title":"Blood"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Salguero-Ar, A.C., Sancho-Mensat, D., Canals-Lorente, B., Sultan, S., Reginald, A., and Chapman, L. (2019). STAT6 knockdown using multiple siRNA sequences inhibits proliferation and induces apoptosis of human colorectal and breast cancer cell lines. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0207558"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6081","DOI":"10.1128\/JVI.78.12.6081-6090.2004","article-title":"Interleukin-13 overexpression by tax transactivation: A potential autocrine stimulus in human T-cell leukemia virus-infected lymphocytes","volume":"78","author":"Schneider","year":"2004","journal-title":"J. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1111\/j.1600-0609.1996.tb01936.x","article-title":"Characterization and regulation of interleukin-4 receptor in adult T-cell leukemia cells","volume":"56","author":"Mori","year":"1996","journal-title":"Eur. J. Haematol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1016\/j.jaci.2019.10.037","article-title":"IL-13 and IL-4, but not IL-5 nor IL-17A, induce hyperresponsiveness in isolated human small airways","volume":"145","author":"Manson","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1038\/leu.2017.13","article-title":"Phosphoproteomic analysis reveals hyperactivation of mTOR\/STAT3 and LCK\/Calcineurin axes in pediatric early T-cell precursor ALL","volume":"31","author":"Serafin","year":"2017","journal-title":"Leukemia"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1182\/blood-2014-06-580480","article-title":"Efficacy of JAK\/STAT pathway inhibition in murine xenograft models of early T-cell precursor (ETP) acute lymphoblastic leukemia","volume":"125","author":"Maude","year":"2015","journal-title":"Blood"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e310","DOI":"10.1097\/HS9.0000000000000310","article-title":"Ruxolitinib Synergizes with Dexamethasone for the Treatment of T-cell Acute Lymphoblastic Leukemia","volume":"3","author":"Verbeke","year":"2019","journal-title":"Hemasphere"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"12480","DOI":"10.1073\/pnas.1516208112","article-title":"Selective targeting of JAK\/STAT signaling is potentiated by Bcl-xL blockade in IL-2-dependent adult T-cell leukemia","volume":"112","author":"Zhang","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1800","DOI":"10.1056\/NEJMoa1917635","article-title":"Ruxolitinib for Glucocorticoid-Refractory Acute Graft-versus-Host Disease","volume":"382","author":"Zeiser","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3789","DOI":"10.1182\/bloodadvances.2020002097","article-title":"The development of ruxolitinib for glucocorticoid-refractory acute graft-versus-host disease","volume":"4","author":"Zeiser","year":"2020","journal-title":"Blood Adv."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1038\/s41375-020-0891-0","article-title":"The Janus kinase 1\/2 inhibitor ruxolitinib in COVID-19 with severe systemic hyperinflammation","volume":"34","author":"Bremer","year":"2020","journal-title":"Leukemia"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1182\/blood-2016-03-643544","article-title":"The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia","volume":"127","author":"Arber","year":"2016","journal-title":"Blood"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1002\/pbc.25469","article-title":"Long-term results of the AIEOP LNH-97 protocol for childhood lymphoblastic lymphoma","volume":"62","author":"Pillon","year":"2015","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2086","DOI":"10.3324\/haematol.2015.139162","article-title":"Results and conclusions of the European Intergroup EURO-LB02 trial in children and adolescents with lymphoblastic lymphoma","volume":"102","author":"Landmann","year":"2017","journal-title":"Haematologica"},{"key":"ref_48","first-page":"332","article-title":"Classification, staging and end results of treatment of childhood non-Hodgkin\u2019s lymphomas: Dissimilarities from lymphomas in adults","volume":"7","author":"Murphy","year":"1980","journal-title":"Semin. Oncol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"9440","DOI":"10.1073\/pnas.1530509100","article-title":"Statistical significance for genome-wide experiments","volume":"100","author":"Storey","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e00149","DOI":"10.1002\/prp2.149","article-title":"Analysis of drug combinations: Current methodological landscape","volume":"3","author":"Foucquier","year":"2015","journal-title":"Pharmacol. Res. Perspect."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/15\/3724\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:34:29Z","timestamp":1760164469000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/15\/3724"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,24]]},"references-count":50,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["cancers13153724"],"URL":"https:\/\/doi.org\/10.3390\/cancers13153724","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,24]]}}}