{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T01:56:47Z","timestamp":1790647007058,"version":"4.1.0"},"reference-count":0,"publisher":"American Society of Hematology","license":[{"start":{"date-parts":[[2023,4,6]],"date-time":"2023-04-06T00:00:00Z","timestamp":1680739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:p>T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with a dismal prognosis related to refractory\/relapsing diseases, raising the need for new targeted-therapies. Activating mutations of the IL7-receptor pathway genes (IL7Rp) play a proven leukemia-supportive role in T-ALL. JAK-inhibitors such as ruxolitinib have recently demonstrated preclinical efficacy. However, prediction markers for sensitivity to JAK-inhibitors are still lacking. Herein, we show that IL7R (CD127) expression is more frequent (~70%) than IL7Rp-mutations in T-ALL (~30%). We compared the so-called non-expressers (no IL7R-expression\/IL7Rp-mutation), expressers (IL7R-expression without IL7Rp-mutation) and mutants (IL7Rp-mutations). Integrative multi-omics analysis outlined IL7R-deregulation in virtually all T-ALL subtypes, at the epigenetic-level in non-expressers, genetic-level in mutants, and post-transcriptional level in expressers. Ex-vivo data using primary-derived xenografts support that IL7Rp is functional whenever the IL7R is expressed, regardless of the IL7Rp mutational status. Consequently, ruxolitinib impaired T-ALL survival in both expressers and mutants. Interestingly, we show that expressers displayed ectopic IL7R-expression and IL7Rp-addiction conferring a deeper sensitivity to ruxolitinib. Conversely, mutants were more sensitive to venetoclax than expressers. Overall, combination of ruxolitinib and venetoclax resulted in synergistic effects in both groups. We illustrate the clinical relevance of this association by reporting achievement of complete remission in two patients with refractory\/relapsed-T-ALL. This provides proof of concept for translation of this strategy into clinics as bridge to transplant. Altogether, IL7R-expression can be used as a biomarker for sensitivity to JAK-inhibition, thereby expanding the fraction of T-ALL patients eligible to ruxolitinib up to nearly ~70% of T-ALL.<\/jats:p>","DOI":"10.1182\/blood.2022017948","type":"journal-article","created":{"date-parts":[[2023,4,6]],"date-time":"2023-04-06T20:01:46Z","timestamp":1680811306000},"update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":16,"title":["IL7-receptor expression is frequent in T-cell acute lymphoblastic leukemia and predicts sensitivity to JAK-inhibition"],"prefix":"10.1182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4156-3008","authenticated-orcid":false,"given":"Lucien","family":"Courtois","sequence":"first","affiliation":[{"name":"Institut Necker Enfants-Malades, INSERM U1151, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurelie","family":"Cabannes-Hamy","sequence":"additional","affiliation":[{"name":"Centre Hospitalier de Versailles, Le Chesnay, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9987-7237","authenticated-orcid":false,"given":"Rathana","family":"Kim","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9 - Hopital Saint-Louis APHP - INSERM U944, PARIS, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9017-9516","authenticated-orcid":false,"given":"Marine","family":"Delecourt","sequence":"additional","affiliation":[{"name":"APHP Hopital Necker Enfants Malades, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine","family":"Pinton","sequence":"additional","affiliation":[{"name":"Institut Necker Enfants-Malades, INSERM U1151, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5615-1287","authenticated-orcid":false,"given":"Guillaume","family":"Charbonnier","sequence":"additional","affiliation":[{"name":"Hopital Necker Enfants-Malades, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9lanie","family":"F\u00e9roul","sequence":"additional","affiliation":[{"name":"Laboratory of Onco-Hematology, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), H\u00f4pital Necker Enfants-Malades, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7209-9287","authenticated-orcid":false,"given":"Charlotte","family":"Smith","sequence":"additional","affiliation":[{"name":"Institut Necker Enfants Malades, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Tueur","sequence":"additional","affiliation":[{"name":"H\u00f4pital Necker Enfants-Malades, Laboratoire d'Onco-H\u00e9matologie, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecile","family":"Pivert","sequence":"additional","affiliation":[{"name":"H\u00f4pital Necker Enfants-Malades, Laboratoire d'Onco-H\u00e9matologie, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6792-1291","authenticated-orcid":false,"given":"Estelle","family":"Balducci","sequence":"additional","affiliation":[{"name":"H\u00f4pital Necker-Enfants Malades, APHP, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"Simonin","sequence":"additional","affiliation":[{"name":"Institut Necker Enfants-Malades, INSERM U1151, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laure H\u00e9l\u00e8ne","family":"Angel","sequence":"additional","affiliation":[{"name":"Assistance Publique-H\u00f4pitaux de Paris (AP-HP), H\u00f4pital Necker Enfants-Malades, Paris, France, Paris, Alabama, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8101-7108","authenticated-orcid":false,"given":"Salvatore","family":"Spicuglia","sequence":"additional","affiliation":[{"name":"Inserm, MArseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2091-7927","authenticated-orcid":false,"given":"Nicolas","family":"Boissel","sequence":"additional","affiliation":[{"name":"Hopital Saint-Louis, AP-HP, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0289-4952","authenticated-orcid":false,"given":"Guillaume P","family":"Andrieu","sequence":"additional","affiliation":[{"name":"Institut Necker Enfants-Malades, INSERM U1151, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vahid","family":"Asnafi","sequence":"additional","affiliation":[{"name":"H\u00f4pital Necker Enfants-Malades, Laboratoire d'Onco-H\u00e9matologie, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3238-4494","authenticated-orcid":false,"given":"Philippe","family":"Rousselot","sequence":"additional","affiliation":[{"name":"Centre Hospitalier de Versailles, Le Chesnay, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludovic","family":"Lhermitte","sequence":"additional","affiliation":[{"name":"H\u00f4pital Necker Enfants-Malades, Laboratoire d'Onco-H\u00e9matologie, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), 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