New Developments in Chronic Myeloid Leukemia: Implications for Therapy
| Autor: | Abolfazl Movafagh, Sanaz Tabarestani |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cancer Research Chronic Myeloid Leukemia Spleen Context (language use) Review Article Tyrosine Kinase Inhibitors 03 medical and health sciences Bcr abl1 0302 clinical medicine hemic and lymphatic diseases Genetics medicine Genetics (clinical) business.industry Myeloid leukemia Imatinib BCR-ABL1 Peripheral blood 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Myeloid cells Cancer research Bone marrow business medicine.drug |
| Zdroj: | Iranian Journal of Cancer Prevention |
| ISSN: | 2008-2401 2008-2398 |
| Popis: | Context: Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by overproduction of immature and matured myeloid cells in the peripheral blood, bone marrow and spleen. Evidence Acquisition: A hallmark of CML is the presence of (9; 22) (q34; q11) reciprocal translocation, which is cytogenetically visible as Philadelphia chromosome (Ph) and results in the formation of BCR-ABL1 fusion protein. This fusion protein is a constitutively active tyrosine kinase which is necessary and sufficient for malignant transformation. The introduction of imatinib, a BCR-ABL1- targeting tyrosine kinase inhibitor (TKI) has revolutionized CML therapy. Subsequently, two other TKIs with increased activity against BCR-ABL1, dasatinib and nilotinib, were developed and approved for CML patients. Nevertheless, CML therapy faces major challenges. Results: The first is the development of resistance to BCR-ABL1 inhibitors in some patients, which can be due to BCR-ABL1 overexpression, differences in cellular drug influx and efflux, activation of alternative signaling pathways, or emergence of BCR-ABL1 kinase domain mutations during TKI treatment. The second is the limited efficiency of BCR-ABL1-TKIs in blast crisis (BC) CML. The third is the insensitivity of CML stem cells to BCR-ABL1 inhibitors. Conventional chemotherapeutics and BCR-ABL1 inhibitors which act by inhibiting cell proliferation and inducing apoptosis, are ineffective against quiescent CML stem cells. Conclusions: A better understanding of the mechanisms that underlie TKI resistance, progression to BC, genomic instability and stem cell quiescence is essential to develop curative strategies for patients with CML. |
| Databáze: | OpenAIRE |
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