98%
921
2 minutes
20
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.leukres.2020.106494 | DOI Listing |
Cureus
June 2025
Department of Medicine, College of Medicine, King Saud University, Riyadh, SAU.
Tyrosine kinase inhibitors (TKIs) have transformed outcomes in chronic myeloid leukemia (CML) and FLT3-mutated acute myeloid leukemia (AML), yet durable remissions are curtailed by the emergence of drug resistance. This review summarizes the principal mechanisms that underlie that resistance. In CML, the most common mechanism is the development of point mutations in the BCR::ABL1 kinase domain (KD).
View Article and Find Full Text PDFCancers (Basel)
May 2025
Department of Hematopathology and Lab Medicines, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
Myeloproliferative neoplasms (MPNs) are a group of rare blood cancers characterized by the excessive production of blood cells in the bone marrow. These disorders arise from acquired genetic driver mutations, with or without underlying genetic predispositions, resulting in the uncontrolled production of red blood cells, white blood cells, or platelets. The excessive cell production and abnormal signaling from driver mutations cause chronic inflammation and a higher risk of blood clots and vascular complications.
View Article and Find Full Text PDFCureus
April 2025
Pediatrics, Global Leukemia Cell-Line Assembly Network, University of Yamanashi, Chuo, JPN.
Background Recent genomic analyses of poor prognostic and relapsed leukemia have revealed the involvement of diverse gene mutations in treatment resistance. These gene mutations are classified into two groups: mutations involving resistance to specific agents such as the fusion gene mutations (typically T315I mutation) in tyrosine kinase inhibitor (TKI) resistance and those involving the resistance to diverse therapeutic modalities such as the gene mutations. In the latter type, although their associations with drug resistance have been clinically demonstrated, the direct association with resistance to each therapeutic modality remains to be fully elucidated.
View Article and Find Full Text PDFCell Commun Signal
April 2025
Department of Biology, University of Rome Tor Vergata, Rome, Italy.
Background: About 40% of relapsed or non-responder tumors exhibit therapeutic resistance in the absence of a clear genetic cause, suggesting a pivotal role of intracellular communication. A deeper understanding of signaling pathways rewiring occurring in resistant cells is crucial to propose alternative effective strategies for cancer patients.
Methods: To achieve this goal, we developed a novel multi-step strategy, which integrates high sensitive mass spectrometry-based phosphoproteomics with network-based analysis.
Int J Hematol
August 2025
Global Leukemia Cell-Line Assembly Network and Department of Pediatrics, School of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409 - 3898, Japan.
In Philadelphia chromosome-positive (Ph +) leukemia, substitution of threonine at the 315 position of BCR::ABL1 with isoleucine (T315I) induces severe resistance to tyrosine kinase inhibitors (TKIs). Of clinical importance, the substitution of the baseline T315I mutation by methionine (I315M) was reported in a Ph + leukemia patient treated with ponatinib. The resultant T315M mutation induces severe TKI-resistance in a murine Ba/F3 model.
View Article and Find Full Text PDF