{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,8]],"date-time":"2026-11-08T04:53:18Z","timestamp":1794113598821,"version":"4.8.0"},"reference-count":32,"publisher":"Ferrata Storti Foundation (Haematologica)","issue":"6","license":[{"start":{"date-parts":[[2020,5,28]],"date-time":"2020-05-28T00:00:00Z","timestamp":1590624000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/legalcode"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["haematol"],"abstract":"<jats:p>Early recognition of Ph-like acute lymphoblastic leukemia cases could impact on the management and outcome of this subset of B-lineage ALL. To assess the prognostic value of the Ph-like status in a pediatric-inspired, minimal residual disease (MRD)-driven trial, we screened 88 B-lineage ALL cases negative for the major fusion genes (BCR-ABL1, ETV6-RUNX1, TCF3-PBX1 and KTM2Ar) enrolled in the GIMEMA LAL1913 front-line protocol for adult BCR\/ABL1-negative ALL. The screening - performed using the BCR\/ABL1-like predictor - identified 28 Ph-like cases (31.8%), characterized by CRLF2 overexpression (35.7%), JAK\/STAT pathway mutations (33.3%), IKZF1 (63.6%), BTG1 (50%) and EBF1 (27.3%) deletions, and rearrangements targeting tyrosine kinases or CRLF2 (40%). The correlation with outcome highlighted that: i) the complete remission (CR) rate was significantly lower in Ph-like compared to non-Ph-like cases (74.1% vs 91.5%, p=0.044); ii) at time point 2 (TP2), decisional for transplant allocation, 52.9% of Ph-like cases vs 20% of non-Ph-like were MRD-positive (p=0.025); iii) the Ph-like profile was the only parameter associated with a higher risk of being MRD-positive at TP2 (p=0.014); iv) at 24 months, Ph-like patients had a significantly inferior event-free and disease-free survival compared to non-Ph-like patients (33.5% vs 66.2%, p=0.005 and 45.5% vs 72.3%, p=0.062, respectively). This study documents that Ph-like patients have a lower CR rate, EFS and DFS, as well as a greater MRD persistence also in a pediatric-oriented and MRD-driven adult ALL protocol, thus reinforcing that the early recognition of Ph-like ALL patients at diagnosis is crucial to refine risk-stratification and to optimize therapeutic strategies.<\/jats:p>","DOI":"10.3324\/haematol.2020.247973","type":"journal-article","created":{"date-parts":[[2020,5,28]],"date-time":"2020-05-28T13:15:40Z","timestamp":1590671740000},"page":"1559-1568","source":"Crossref","is-referenced-by-count":74,"title":["Philadelphia-like acute lymphoblastic leukemia is associated with minimal residual disease persistence and poor outcome. First report of the minimal residual disease-oriented GIMEMA LAL1913"],"prefix":"10.3324","volume":"106","author":[{"family":"Sabina Chiaretti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Monica Messina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Irene Della Starza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Alfonso Piciocchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Luciana Cafforio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Marzia Cavalli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Akram Taherinasab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Michela Ansuinelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Loredana Elia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Guglielmo Albertini Petroni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Roberta La Starza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Martina Canichella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Alessia Lauretti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Maria Ctristina Puzzolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Valentina Pierini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Alessandra Santoro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Orietta Spinelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Valerio Apicella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Saveria Capria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Francesco Di Raimondo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Paolo De Fabritiis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Cristina Papayannidis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Anna Candoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Roberto Cairoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Marco Cerrano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Nicola Fracchiolla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Daniele Mattei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Chiara Cattaneo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Antonella Vitale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Enrico Crea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Paola Fazi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Cristina Mecucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Alessandro Rambaldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Anna Guarini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Renato Bassan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Robin Fo\u00e0","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1856","published-online":{"date-parts":[[2020,5,28]]},"reference":[{"key":"25818","doi-asserted-by":"crossref","unstructured":"Den Boer ML, van Slegtenhorst M, De Menezes RX. 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Tyrosine kinase inhibitor therapy induces remission in a patient with refractory EBF1- PDGFRB-positive acute lymphoblastic leukemia. J Clin Oncol. 2013; 31(25):e413-416.","DOI":"10.1200\/JCO.2012.47.6770"},{"key":"25828","doi-asserted-by":"crossref","unstructured":"Fazio F, Barberi W, Cazzaniga G. Efficacy of imatinib and chemotherapy in a pediatric patient with Philadelphia-like acute lymphoblastic leukemia with EBF1- PDGFRB fusion transcript. Leuk Lymphoma. 2020; 61(2):469-472.","DOI":"10.1080\/10428194.2019.1668938"},{"key":"25829","doi-asserted-by":"crossref","unstructured":"Tasian SK, Teachey DT, Li Y. Potent efficacy of combined PI3K\/mTOR and JAK or ABL inhibition in murine xenograft models of Ph-like acute lymphoblastic leukemia. Blood. 2017; 129(2):177-187.","DOI":"10.1182\/blood-2016-05-707653"},{"key":"25830","doi-asserted-by":"crossref","unstructured":"Harvey RC, Kang H, Roberts KG. Development and validation of a highly sensitive and specific gene expression classifier to prospectively screen and identify B-precursor acute lymphoblastic leukemia (ALL) patients with a Philadelphia chromosomelike (\u201cPh-like\u201d or \u201cBCR-ABL1-Like\u201d) signature for therapeutic targeting and clinical intervention. Blood. 2013; 122(21):826.","DOI":"10.1182\/blood.V122.21.826.826"},{"key":"25831","doi-asserted-by":"crossref","unstructured":"Heatley SL, Sadras T, Kok CH. High prevalence of relapse in children with Philadelphia-like acute lymphoblastic leukemia despite risk-adapted treatment. Haematologica. 2017; 102(12):e490-e493.","DOI":"10.3324\/haematol.2016.162925"},{"key":"25832","doi-asserted-by":"crossref","unstructured":"Roberts KG. The biology of Philadelphia chromosome-like ALL. Best Pract Res Clin Haematol. 2017; 30(3):212-221.","DOI":"10.1016\/j.beha.2017.07.003"},{"key":"25833","doi-asserted-by":"crossref","unstructured":"Roberts KG, Pei D, Campana D. 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The Validation of the BCR\/ABL1-like predictor across laboratories shows reproducibility of results. Blood. 2019; 134(Suppl 1):S5211.","DOI":"10.1182\/blood-2019-122116"},{"key":"25847","doi-asserted-by":"crossref","unstructured":"Chiaretti S, Messina M, Fo\u00e0 R. BCR\/ABL1- like acute lymphoblastic leukemia: how to diagnose and treat?. Cancer. 2019; 125(2):194-204.","DOI":"10.1002\/cncr.31848"},{"key":"25848","doi-asserted-by":"crossref","unstructured":"Tanasi I, Ba I, Sirvent N. Efficacy of tyrosine kinase inhibitors in Ph-like acute lymphoblastic leukemia harboring ABLclass rearrangements. Blood. 2019; 134(16):1351-1355.","DOI":"10.1182\/blood.2019001244"},{"key":"25849","doi-asserted-by":"crossref","unstructured":"Fo\u00e0 R, Bassan R, Vitale A. GIMEMA Investigators. Dasatinib-nlinatumomab for Ph-positive acute lymphoblastic leukemia in adults. 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