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Review
. 2024 Jan 1;20(1):175-181.
doi: 10.7150/ijbs.86305. eCollection 2024.

Mechanisms underlying therapeutic resistance of tyrosine kinase inhibitors in chronic myeloid leukemia

Jingnan Sun  1 , Ruiping Hu  1 , Mengyuan Han  1 , Yehui Tan  1 , Mengqing Xie  1   2 , Sujun Gao  1 , Ji-Fan Hu  1   3
Affiliations
Review

Mechanisms underlying therapeutic resistance of tyrosine kinase inhibitors in chronic myeloid leukemia

Jingnan Sun et al. Int J Biol Sci. .

Abstract

Chronic myeloid leukemia (CML) is a malignant clonal disease involving hematopoietic stem cells that is characterized by myeloid cell proliferation in bone marrow and peripheral blood, and the presence of the Philadelphia (Ph) chromosome with BCR-ABL fusion gene. Treatment of CML has dramatically improved since the advent of tyrosine kinase inhibitors (TKI). However, there are a small subset of CML patients who develop resistance to TKI. Mutations in the ABL kinase domain (KD) are currently recognized as the leading cause of TKI resistance in CML. In this review, we discuss the concept of resistance and summarize recent advances exploring the mechanisms underlying CML resistance. Overcoming TKI resistance appears to be the most successful approach to reduce the burden of leukemia and enhance cures for CML. Advances in new strategies to combat drug resistance may rapidly change the management of TKI-resistant CML and expand the prospects for available therapies.

Keywords: ABL mutation; TKI Resistance; chronic myeloid leukemia; mechanism.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
Mechanisms of TKI resistance in CML patients.
Figure 2
Figure 2
The location of hotspot mutations in the kinase domain.
See this image and copyright information in PMC

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