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

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 im...

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Bibliographic Details
Published in:International journal of biological sciences 2024, Vol.20 (1), p.175-181
Main Authors: Sun, Jingnan, Hu, Ruiping, Han, Mengyuan, Tan, Yehui, Xie, Mengqing, Gao, Sujun, Hu, Ji-Fan
Format: Article
Language:English
Subjects:
BCR-ABL protein
Bone marrow
Cell cycle
Cell proliferation
Chromosomes
Chronic myeloid leukemia
Clinical medicine
Drug resistance
Drug Resistance, Neoplasm - genetics
Enzyme inhibitors
Fusion protein
Fusion Proteins, bcr-abl - genetics
Fusion Proteins, bcr-abl - therapeutic use
Gene amplification
Hematopoietic stem cells
Humans
Kinases
Leukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy
Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics
Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology
Mutation
Myeloid leukemia
Peripheral blood
Protein Kinase Inhibitors - pharmacology
Protein Kinase Inhibitors - therapeutic use
Proteins
Review
Stem cells
Tyrosine
Tyrosine Kinase Inhibitors
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Description
Summary: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.
ISSN:1449-2288
1449-2288
DOI:10.7150/ijbs.86305