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Control of Ph+ and additional chromosomal abnormalities in chronic myeloid leukemia by tyrosine kinase inhibitors

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Abstract

Chronic myeloid leukemia (CML) is a type of blood cancer that is known to affect hematopoietic stem cells. The presence of the Philadelphia chromosome (Ph+) is the major characteristic of CML. A protein expressed by the Philadelphia chromosome shows elevated tyrosine kinase activity and is considered a tumorigenic factor. The first line of therapy that had been established for CML was “imatinib,” a potent tyrosine kinase inhibitor. Various other second- and third-generation TKIs are taken into account in cases of imatinib failure/resistance. With the subsequent rise in the development of tyrosine kinase inhibitors, optimization in the treatment of CML and amplified total survival were observed throughout TKI dosage. As the disease progresses, additional chromosomal abnormalities (ACAs) have been reported, but their prognostic effect and impact on the response to treatment are still unknown. However, some substantial understandings have been achieved into the disease transformation mechanisms, including the role of somatic mutations, ACAs, and several different genomic mutations that occur during diagnosis or have evolved during treatment. The acquisition of ACAs impedes CML treatment. Due to additional chromosomal lesions, there are greater chances of future disease progression at the time of CML diagnosis beyond the Ph+ translocation. The synchronous appearance of two or more ACAs leads to lower survival and is classified as a poor prognostic group. The key objective of this review is to provide detailed insights into TKIs and their role in controlling Ph+ and ACAs, along with their response, treatment, overall persistence, and survival rate.

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Acknowledgements

MV acknowledges the support he received from the Banaras Hindu University, Varanasi, under the IOE incentive grant in writing this manuscript. SA is grateful to BHU for the award of the UGC Non-NET fellowship.

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    Sana Ansari & Malkhey Verma

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MV conceived and designed this review. SA collected the data and prepared the first draft of the manuscript. Further, the manuscript was improved iteratively by MV and SA. Authors have read and approved the final manuscript.

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Ansari, S., Verma, M. Control of Ph+ and additional chromosomal abnormalities in chronic myeloid leukemia by tyrosine kinase inhibitors. Med Oncol 40, 237 (2023). https://doi.org/10.1007/s12032-023-02116-4

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