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Chronic myelogenous leukemia

Chronic myeloid leukemia: the concepts of resistance and persistence and the relationship with the BCR-ABL1 transcript type

Leukemia volume 33, pages 2358–2364 (2019)Cite this article

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Abstract

Chronic myeloid leukemia is driven by a hybrid gene, BCR-ABL1, that codes for a leukemogenic tyrosine kinase (TK) protein of 210 KDa (p210BCR-ABL1). Resistance to TK inhibitor (TKI) therapy occurs in relatively few patients, no more than 10%, while persistence of minimal residual disease during TKI therapy occurs in the great majority of patients. Resistance is a cause of death, persistence is compatible with a fairly normal length and quality of life, but may require lifelong treatment. The causes of resistance are heterogeneous, including the development of other genomic abnormalities or the altered expression of other genes, requiring different treatments. The causes of persistence may not be the same as those of resistance. We hypothesize that the variability in breakpoint position within the Major-breakpoint cluster region (M-bcr), resulting in two different messenger RNAs that may or may not include exon 14 of BCR (e13a2 and e14a2, respectively), and, as a consequence, in two p210BCR-ABL1 proteins that differ by 25 amino acids, may be a cause of persistence. The hypothesis is based on a critical review of the relationships between the BCR-ABL1 transcript types, the response to TKIs, the outcome of treatment, and the immune response, suggesting that the e14a2 transcript is associated with more and deeper molecular responses, hence with a higher probability of achieving treatment-free remission (TFR). Investigating this putative cause of persistence may help bringing more patients into stable TFR.

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  1. Institute of Hematology “Lorenzo and Ariosto Seràgnoli”, Department of Experimental, Diagnostic and Specialty Medicine, S.Orsola-Malpighi University Hospital, University of Bologna, Bologna, Italy

    Michele Baccarani, Gianantonio Rosti & Simona Soverini

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Baccarani, M., Rosti, G. & Soverini, S. Chronic myeloid leukemia: the concepts of resistance and persistence and the relationship with the BCR-ABL1 transcript type. Leukemia 33, 2358–2364 (2019). https://doi.org/10.1038/s41375-019-0562-1

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