{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T07:03:15Z","timestamp":1790492595652,"version":"4.1.0"},"reference-count":167,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2020,8,12]],"date-time":"2020-08-12T00:00:00Z","timestamp":1597190400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2015\/18\/E\/NZ5\/00723"],"award-info":[{"award-number":["2015\/18\/E\/NZ5\/00723"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004569","name":"Ministerstwo Nauki i Szkolnictwa Wy\u017cszego","doi-asserted-by":"publisher","award":["013\/RID\/2018\/19"],"award-info":[{"award-number":["013\/RID\/2018\/19"]}],"id":[{"id":"10.13039\/501100004569","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Philadelphia chromosome (Ph) results from a translocation between the breakpoint cluster region (BCR) gene on chromosome 9 and ABL proto-oncogene 1 (ABL1) gene on chromosome 22. The fusion gene, BCR-ABL1, is a constitutively active tyrosine kinase which promotes development of leukemia. Depending on the breakpoint site within the BCR gene, different isoforms of BCR-ABL1 exist, with p210 and p190 being the most prevalent. P210 isoform is the hallmark of chronic myeloid leukemia (CML), while p190 isoform is expressed in majority of Ph-positive B cell acute lymphoblastic leukemia (Ph+ B-ALL) cases. The crucial component of treatment protocols of CML and Ph+ B-ALL patients are tyrosine kinase inhibitors (TKIs), drugs which target both BCR-ABL1 isoforms. While TKIs therapy is successful in great majority of CML patients, Ph+ B-ALL often relapses as a drug-resistant disease. Recently, the high-throughput genomic and proteomic analyses revealed significant differences between CML and Ph+ B-ALL. In this review we summarize recent discoveries related to differential signaling pathways mediated by different BCR-ABL1 isoforms, lineage-specific genetic lesions, and metabolic reprogramming. In particular, we emphasize the features distinguishing Ph+ B-ALL from CML and focus on potential therapeutic approaches exploiting those characteristics, which could improve the treatment of Ph+ B-ALL.<\/jats:p>","DOI":"10.3390\/ijms21165776","type":"journal-article","created":{"date-parts":[[2020,8,12]],"date-time":"2020-08-12T09:14:49Z","timestamp":1597223689000},"page":"5776","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Philadelphia Chromosome-Positive Leukemia in the Lymphoid Lineage\u2014Similarities and Differences with the Myeloid Lineage and Specific Vulnerabilities"],"prefix":"10.3390","volume":"21","author":[{"given":"Lukasz","family":"Komorowski","sequence":"first","affiliation":[{"name":"Department of Immunology, Medical University of Warsaw, Nielubowicza 5 St, 02-097 Warsaw, Poland"},{"name":"Postgraduate School of Molecular Medicine, Medical University of Warsaw, Trojdena 2a St, 02-091 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaudyna","family":"Fidyt","sequence":"additional","affiliation":[{"name":"Department of Immunology, Medical University of Warsaw, Nielubowicza 5 St, 02-097 Warsaw, Poland"},{"name":"Postgraduate School of Molecular Medicine, Medical University of Warsaw, Trojdena 2a St, 02-091 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"El\u017cbieta","family":"Patkowska","sequence":"additional","affiliation":[{"name":"Department of Hematology, Institute of Hematology and Transfusion Medicine, Indiry Gandhi 14, 02-776 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1719-5233","authenticated-orcid":false,"given":"Malgorzata","family":"Firczuk","sequence":"additional","affiliation":[{"name":"Department of Immunology, Medical University of Warsaw, Nielubowicza 5 St, 02-097 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1038\/nrc1567","article-title":"Mechanisms of BCR-ABL in the pathogenesis of chronic myelogenous leukaemia","volume":"5","author":"Ren","year":"2005","journal-title":"Nat. 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