{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:58:44Z","timestamp":1760151524001,"version":"build-2065373602"},"reference-count":43,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,3,25]],"date-time":"2022-03-25T00:00:00Z","timestamp":1648166400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"National Council for Scientific and Technological Development","doi-asserted-by":"publisher","award":["2021"],"award-info":[{"award-number":["2021"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The Philadelphia (Ph+) chromosome, t(9;22)(q34;q11.2), originates from a chimeric gene called BCR-ABL and is present in more than 90% of CML patients. Most patients with CML express the protein p210 BCR-ABL and, with a frequency lower than 5%, express rare isoforms, the main one being p190. In the transition from the chronic phase to the blast phase (BP), additional chromosomal abnormalities, such as the presence of the double Ph+ chromosome, are revealed. Of the 1132 patients analyzed via molecular biology in this study, two patients (0.17%) showed the co-expression of the p210 and p190 isoforms for the BCR-ABL transcript, with the concomitant presence of a double Ph+ chromosome, which was observed via conventional cytogenetics and confirmed by fluorescent in situ hybridization. The BCR-ABL\/ABL% p210 and p190 ratio increased in these two patients from diagnosis to progression to blast crisis. To our knowledge, this is the first report in the literature of patients who co-expressed the two main BCR-ABL transcript isoforms and concomitantly presented Ph+ chromosome duplication. The evolution from the chronic phase to BP often occurs within 5 to 7 years, and, in this study, the evolution to BP was earlier, since disease-free survival was on average 4.5 months and overall survival was on average 9.5 months. The presence of the p190 transcript and the double Ph+ chromosome in CML may be related to the vertiginous progression of the disease.<\/jats:p>","DOI":"10.3390\/genes13040580","type":"journal-article","created":{"date-parts":[[2022,3,25]],"date-time":"2022-03-25T15:31:21Z","timestamp":1648222281000},"page":"580","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chronic Myelogenous Leukemia with Double Philadelphia Chromosome and Coexpression of p210 and p190 Fusion Transcripts"],"prefix":"10.3390","volume":"13","author":[{"given":"Samara Silveira da","family":"Cruz","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Biology, Ophir Loyola Hospital, Bel\u00e9m 66063-240, Brazil"},{"name":"Human Cytogenetics Laboratory, Biological Science Institute, Federal University of Par\u00e1, Bel\u00e9m 66075-110, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aline Damasceno","family":"Seabra","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Ophir Loyola Hospital, Bel\u00e9m 66063-240, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lais Helena Rescinho","family":"Macambira","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Ophir Loyola Hospital, Bel\u00e9m 66063-240, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2199-4246","authenticated-orcid":false,"given":"D\u00e9bora Monteiro","family":"Carneiro","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Ophir Loyola Hospital, Bel\u00e9m 66063-240, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8137-1596","authenticated-orcid":false,"given":"Patr\u00edcia Ferreira","family":"Nunes","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Ophir Loyola Hospital, Bel\u00e9m 66063-240, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thais Brilhante","family":"Pontes","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Ophir Loyola Hospital, Bel\u00e9m 66063-240, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando Augusto Rodrigues","family":"Mello-Junior","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Ophir Loyola Hospital, Bel\u00e9m 66063-240, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucyana Barbosa Cardoso","family":"Le\u00e3o","sequence":"additional","affiliation":[{"name":"Department of Hematology, Ophir Loyola Hospital, Bel\u00e9m 66063-240, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernanda de Nazar\u00e9 Cardoso dos Santos","family":"Cordeiro","sequence":"additional","affiliation":[{"name":"Department of Hematology, Ophir Loyola Hospital, Bel\u00e9m 66063-240, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thiago Xavier","family":"Carneiro","sequence":"additional","affiliation":[{"name":"Department of Hematology, Ophir Loyola Hospital, Bel\u00e9m 66063-240, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5845-3481","authenticated-orcid":false,"given":"Caroline Aquino","family":"Moreira-Nunes","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Ophir Loyola Hospital, Bel\u00e9m 66063-240, Brazil"},{"name":"Pharmacogenetics Laboratory, Department of Medicine, Drug Research and Development Center (NPDM), Federal University of Cear\u00e1, Fortaleza 60430-275, Brazil"},{"name":"Northeast Biotechnology Network (RENORBIO), Itaperi Campus, Cear\u00e1 State University, Fortaleza 60740-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4872-234X","authenticated-orcid":false,"given":"Rommel Mario Rodr\u00edguez","family":"Burbano","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Ophir Loyola Hospital, Bel\u00e9m 66063-240, Brazil"},{"name":"Human Cytogenetics Laboratory, Biological Science Institute, Federal University of Par\u00e1, Bel\u00e9m 66075-110, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/243290a0","article-title":"A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining","volume":"243","author":"Rowley","year":"1973","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Abdulmawjood, B., Costa, B., Roma-Rodrigues, C., Baptista, P.V., and Fernandes, A.R. (2021). Genetic Biomarkers in Chronic Myeloid Leukemia: What Have We Learned So Far?. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222212516"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/0092-8674(92)90241-4","article-title":"Dominant negative MYC blocks transformation by ABL oncogenes","volume":"70","author":"Sawyers","year":"1992","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1038\/nrc2147","article-title":"Chronic myeloid leukaemia as a model of disease evolution in human cancer","volume":"7","author":"Melo","year":"2007","journal-title":"Nat. Rev. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1002\/ajh.23691","article-title":"Chronic myeloid leukemia: 2014 update on diagnosis, monitoring, and management","volume":"89","author":"Jabbour","year":"2014","journal-title":"Am. J. Hematol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1007\/s11010-022-04376-6","article-title":"Transport and metabolism of tyrosine kinase inhibitors associated with chronic myeloid leukemia therapy: A review","volume":"477","author":"Kumar","year":"2022","journal-title":"Mol. Cell. Biochem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1006\/scbi.2001.0387","article-title":"Molecular evolution of chronic myeloid leukaemia","volume":"11","author":"Shteper","year":"2001","journal-title":"Semin. Cancer Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"S241","DOI":"10.1007\/s00277-015-2314-2","article-title":"Epidemiology of chronic myeloid leukaemia: An update","volume":"94","author":"Sandin","year":"2015","journal-title":"Ann. Hematol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1016\/j.clml.2015.09.007","article-title":"Prognostic Factors, Response to Treatment, and Survival in Patients With Chronic Myeloid Leukemia in Blast Phase: A Single-Institution Survey","volume":"15","author":"Aguayo","year":"2015","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2232","DOI":"10.1182\/blood-2009-02-204693","article-title":"Chronic myeloid leukemia (CML) with p190 BCR-ABL: Analysis of characteristics, outcomes, and prognostic significance","volume":"114","author":"Verma","year":"2009","journal-title":"Blood"},{"key":"ref_11","first-page":"850","article-title":"Heterogeneity of BCR-ABL rearrangement in patients with chronic myeloid leukemia in Pakistan","volume":"30","author":"Tabassum","year":"2014","journal-title":"Pak. J. Med. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e193","DOI":"10.1097\/MPH.0000000000000582","article-title":"Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia or Chronic Myeloid Leukemia in Lymphoid Blast Crisis","volume":"38","author":"Kolenova","year":"2016","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"ref_13","first-page":"5171","article-title":"Coexistence of p210BCR-ABL and CBF\u03b2-MYH11 fusion genes in myeloid leukemia: A report of 4 cases","volume":"14","author":"Wang","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e549","DOI":"10.3324\/haematol.2018.192534","article-title":"A double Philadelphia chromosome-positive chronic myeloid leukemia patient, co-expressing P210BCR-ABL1 and P195BCR-ABL1 isoforms","volume":"103","author":"Vinhas","year":"2018","journal-title":"Haematologica"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1964","DOI":"10.1038\/s41375-020-01082-4","article-title":"Characterization of p190-Bcr-Abl chronic myeloid leukemia reveals specific signaling pathways and therapeutic targets","volume":"35","author":"Kim","year":"2021","journal-title":"Leukemia"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"6760","DOI":"10.1182\/blood-2011-08-373902","article-title":"Impact of additional cytogenetic aberrations at diagnosis on prognosis of CML: Long-term observation of 1151 patients from the randomized CML Study IV","volume":"118","author":"Fabarius","year":"2011","journal-title":"Blood"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1111\/j.1751-553X.2007.00957.x","article-title":"Double Philadelphia-chromosome: A resistance factor on the imatinib mesylate therapy for chronic myeloid leukemia","volume":"30","author":"Otero","year":"2008","journal-title":"Int. J. Lab. Hematol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e130-3","DOI":"10.1200\/JCO.2013.51.1188","article-title":"Molecular Response of e19a2 BCR-ABL1 Chronic Myeloid Leukemia With Double Philadelphia Chromosome to Dasatinib","volume":"34","author":"Ikeda","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_19","first-page":"253","article-title":"Identification of two Robertsonian translocations with a Giemsa banding technique","volume":"15","author":"Scheres","year":"1972","journal-title":"Humangenetik"},{"key":"ref_20","unstructured":"McGowan-Jordan, J., Hastings, R., and Moore, S. (2020). ISCN. An International System for Human Cytogenomic Nomenclature, Karger AG."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/BF00500631","article-title":"In situ hybridization as a tool to study numerical chromosome aberrations in solid bladder tumors","volume":"89","author":"Hopman","year":"1988","journal-title":"Histochemistry"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1186\/s13256-021-02885-4","article-title":"A unique three-way Philadelphia chromosome variant t(4;9;22)(q21;q34;q11.2) in a newly diagnosed patient with chronic phase chronic myeloid leukemia: A case report and review of the literature","volume":"15","author":"Torii","year":"2021","journal-title":"J. Med. Case Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2074","DOI":"10.1038\/s41375-020-0826-9","article-title":"High-risk additional chromosomal abnormalities at low blast counts herald death by CML","volume":"34","author":"Hehlmann","year":"2020","journal-title":"Leukemia"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3163","DOI":"10.1182\/blood-2010-10-314682","article-title":"Mixed-phenotype acute leukemia: Clinical and laboratory features and outcome in 100 patients defined according to the WHO 2008 classification","volume":"117","author":"Matutes","year":"2011","journal-title":"Blood"},{"key":"ref_25","first-page":"25","article-title":"Mixed Phenotype Acute Leukemia with Two Immunophenotypically Distinct B and T Blasts Populations, Double Ph+ Chromosome and Complex Karyotype: Report of an Unusual Case","volume":"8","author":"Kohla","year":"2015","journal-title":"Clin. Med. Insights Blood Disord."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1038\/leu.2011.7","article-title":"p53 stabilization induces apoptosis in chronic myeloid leukemia blast crisis cells","volume":"25","author":"Peterson","year":"2011","journal-title":"Leukemia"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1080\/15384047.2016.1219821","article-title":"Novel BCR-ABL1 fusion and leukemic mutations of SETBP1, PAX5, and TP53 detected by next generation sequencing in chronic myeloid leukemia","volume":"17","author":"Fu","year":"2016","journal-title":"Cancer Biol. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4808","DOI":"10.1182\/blood-2008-07-077958","article-title":"Translation of the Philadelphia chromosome into therapy for CML","volume":"112","author":"Druker","year":"2008","journal-title":"Blood"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.leukres.2018.10.002","article-title":"A phase I clinical trial of ruxolitinib in combination with nilotinib in chronic myeloid leukemia patients with molecular evidence of disease","volume":"74","author":"Sweet","year":"2018","journal-title":"Leuk. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1056\/NEJMoa011573","article-title":"Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia","volume":"346","author":"Kantarjian","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3331","DOI":"10.1182\/blood-2012-08-452409","article-title":"Integrating in vitro sensitivity and dose-response slope is predictive of clinical response to ABL kinase inhibitors in chronic myeloid leukemia","volume":"122","author":"Vainstein","year":"2013","journal-title":"Blood"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1186\/s40064-015-0930-x","article-title":"Coexistence of P190 and P210 BCR\/ABL transcripts in chronic myeloid leukemia blast crisis resistant to imatinib","volume":"4","author":"Junmei","year":"2015","journal-title":"Springerplus"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"850","DOI":"10.3892\/etm.2015.2173","article-title":"Extramedullary T-lymphoblastic blast crisis in chronic myelogenous leukemia: A case report of successful diagnosis and treatment","volume":"9","author":"Zeng","year":"2015","journal-title":"Exp. Ther. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.beha.2007.11.010","article-title":"Is it important to decipher the heterogeneity of \u201cnormal karyotype AML\u201d?","volume":"21","author":"Nimer","year":"2008","journal-title":"Best Pract. Res. Clin. Haematol."},{"key":"ref_35","first-page":"472","article-title":"Molecular and genomic landscapes in secondary & therapy related acute myeloid leukemia","volume":"11","author":"Goel","year":"2021","journal-title":"Am. J. Blood Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1111\/bjh.13184","article-title":"Long-term outcome of chronic myeloid leukaemia patients with p210 and p190 co-expression at baseline","volume":"169","author":"Molica","year":"2015","journal-title":"Br. J. Haematol."},{"key":"ref_37","first-page":"65","article-title":"BCR-ABL fusion genes and laboratory findings in patients with chronic myeloid leukemia in northeast Iran","volume":"9","author":"Ayatollahi","year":"2018","journal-title":"Caspian J. Intern. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1007\/s11899-019-00546-4","article-title":"Towards a Personalized Treatment of Patients with Chronic Myeloid Leukemia","volume":"14","author":"Rabian","year":"2019","journal-title":"Curr Hematol Malig. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5213","DOI":"10.1182\/blood.V87.12.5213.bloodjournal87125213","article-title":"P190 BCR-ABL mRNA is expressed at low levels in p210 positive chronic myeloid leukemia and acute lymphoblastic leukemias","volume":"87","author":"Hochaaus","year":"1996","journal-title":"Blood"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/s00277-002-0433-z","article-title":"Lymphoid preponderance and the absence of basophilia and splenomegaly are frequent in m-bcr-positive chronic myelogenous leukemia","volume":"81","author":"Hur","year":"2002","journal-title":"Ann. Hematol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1002\/hon.822","article-title":"First and second line imatinib treatment in chronic myelogenous leukemia patients expressing rare e1a2 or e19a2 BCR-ABL transcripts","volume":"25","author":"Andrikovics","year":"2007","journal-title":"Hematol. Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1007\/s00428-015-1802-z","article-title":"BCR-ABL1 e6a2 transcript in chronic myeloid leukemia: Biological features and molecular monitoring by droplet digital PCR","volume":"467","author":"Zagaria","year":"2015","journal-title":"Virchows Arch."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.cancergencyto.2004.11.010","article-title":"Coexistence of different clonal populations harboring the b3a2 (p210) and e1a2 (p190) BCR-ABL1 fusion transcripts in chronic myelogenous leukemia resistant to imatinib","volume":"160","author":"Agirre","year":"2005","journal-title":"Cancer Genet. Cytogenet."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/4\/580\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:42:55Z","timestamp":1760136175000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/4\/580"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,25]]},"references-count":43,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["genes13040580"],"URL":"https:\/\/doi.org\/10.3390\/genes13040580","relation":{},"ISSN":["2073-4425"],"issn-type":[{"type":"electronic","value":"2073-4425"}],"subject":[],"published":{"date-parts":[[2022,3,25]]}}}