Chronic Myelogenous Leukemia with Double Philadelphia Chromosome and Coexpression of p210 and p190 Fusion Transcripts

• Published in: Genes 2022-03, Vol.13 (4), p.580
• Main Authors: Cruz, Samara Silveira da, Seabra, Aline Damasceno, Macambira, Lais Helena Rescinho, Carneiro, Débora Monteiro, Nunes, Patrícia Ferreira, Pontes, Thais Brilhante, Mello-Junior, Fernando Augusto Rodrigues, Leão, Lucyana Barbosa Cardoso, Cordeiro, Fernanda de Nazaré Cardoso Dos Santos, Carneiro, Thiago Xavier, Moreira-Nunes, Caroline Aquino, Burbano, Rommel Mario Rodríguez
• Format: Article
• Language: English
• Subjects: BCR-ABL protein; Blast crisis; Blast Crisis - genetics; Bone marrow; Chromosome aberrations; Chromosomes; Chronic myeloid leukemia; Cytogenetics; Dehydrogenases; Ethanol; Fluorescence in situ hybridization; Fusion protein; Fusion Proteins, bcr-abl - genetics; Gene duplication; GTP-binding protein; Humans; Hybridization; In Situ Hybridization, Fluorescence; Isoforms; Kinases; Laboratories; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics; Life sciences; Medical prognosis; Myeloid leukemia; Patients; Philadelphia Chromosome; Protein Isoforms - genetics; Proteins; Survival; Transcription
• ISSN: 2073-4425; 2073-4425
• DOI: 10.3390/genes13040580

The Philadelphia (Ph+) chromosome, t(9;22)(q34;q11.2), originates from a chimeric gene called and is present in more than 90% of CML patients. Most patients with CML express the protein p210 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 transcript, with the concomitant presence of a double Ph+ chromosome, which was observed via conventional cytogenetics and confirmed by fluorescent in situ hybridization. The / % 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 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.