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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

CR-ABL1 Tyrosine Kinase Complex Signaling Transduction: Challenges to Overcome Resistance in Chronic Myeloid Leukemi

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Amarante-Mendes, Gustavo P. [1, 2] ; Rana, Aamir [1, 3] ; Datoguia, Tarcila Santos [4] ; Hamerschlak, Nelson [4] ; Brumatti, Gabriela [5, 6]
Total Authors: 5
[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Imunol, BR-05508000 Sao Paulo - Brazil
[2] Inst Invest Imunol, Inst Nacl Ciencia Tecnol INCT, BR-05508000 Sao Paulo - Brazil
[3] Beckman Res Inst City Hope, Dept ImmunoOncol, Duarte, CA 91010 - USA
[4] Hosp Israelita Albert Einstein, BR-05652900 Sao Paulo - Brazil
[5] Walter & Eliza Hall Inst Med Res, Inflammat Div, Melbourne, Vic 3052 - Australia
[6] Univ Melbourne, Dept Med Biol, Melbourne, Vic 3010 - Australia
Total Affiliations: 6
Document type: Journal article
Source: HARMACEUTIC; v. 14, n. 1 JAN 2022.
Web of Science Citations: 0

The constitutively active BCR-ABL1 tyrosine kinase, found in t(9;22)(q34;q11) chromosomal translocation-derived leukemia, initiates an extremely complex signaling transduction cascade that induces a strong state of resistance to chemotherapy. Targeted therapies based on tyrosine kinase inhibitors (TKIs), such as imatinib, dasatinib, nilotinib, bosutinib, and ponatinib, have revolutionized the treatment of BCR-ABL1-driven leukemia, particularly chronic myeloid leukemia (CML). However, TKIs do not cure CML patients, as some develop TKI resistance and the majority relapse upon withdrawal from treatment. Importantly, although BCR-ABL1 tyrosine kinase is necessary to initiate and establish the malignant phenotype of Ph-related leukemia, in the later advanced phase of the disease, BCR-ABL1-independent mechanisms are also in place. Here, we present an overview of the signaling pathways initiated by BCR-ABL1 and discuss the major challenges regarding immunologic/pharmacologic combined therapies. (AU)

FAPESP's process: 15/09568-5 - Role of autophagy in the control of infection by Trypanosoma cruzi and the influence of the innate immunity receptors in this process
Grantee:Kely Catarine Matteucci
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 18/25395-1 - Role of RASSF9 in melanoma using the CRISPR/Cas9 system
Grantee:João Gustavo Pessini Amarante Mendes
Support Opportunities: Regular Research Grants