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Mechanisms of Resistance and Implications for Treatment Strategies in Chronic Myeloid Leukaemia.

ABSTRACT: Tyrosine kinase inhibitors (TKIs) have revolutionised the management of chronic myeloid leukaemia (CML), with the disease now having a five-year survival rate over 80%. The primary focus in the treatment of CML has been on improving the specificity and potency of TKIs to inhibit the activation of the BCR::ABL1 kinase and/or overcoming resistance driven by mutations in the BCR::ABL1 oncogene. However, this approach may be limited in a significant proportion of patients who develop TKI resistance despite the effective inhibition of BCR::ABL1. These patients may require novel therapeutic strategies that target both BCR::ABL1-dependent and BCR::ABL1-independent mechanisms of resistance. The combination treatment strategies that target alternative survival signalling, which may contribute towards BCR::ABL1-independent resistance, could be a successful strategy for eradicating residual leukaemic cells and consequently increasing the response rate in CML patients.

SUBMITTER: Poudel G

PROVIDER: S-EPMC9317051 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Mechanisms of Resistance and Implications for Treatment Strategies in Chronic Myeloid Leukaemia.

Poudel Govinda G Tolland Molly G MG Hughes Timothy P TP Pagani Ilaria S IS

Cancers 20220706 14

Tyrosine kinase inhibitors (TKIs) have revolutionised the management of chronic myeloid leukaemia (CML), with the disease now having a five-year survival rate over 80%. The primary focus in the treatment of CML has been on improving the specificity and potency of TKIs to inhibit the activation of the BCR::ABL1 kinase and/or overcoming resistance driven by mutations in the BCR::ABL1 oncogene. However, this approach may be limited in a significant proportion of patients who develop TKI resistance ...[more]

PMID: 35884363

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