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

Autor(es)

Amarante-Mendes, Gustavo P. ^{[1, 2]} ; Rana, Aamir ^{[1, 3]} ; Datoguia, Tarcila Santos ^[4] ; Hamerschlak, Nelson ^[4] ; Brumatti, Gabriela ^{[5, 6]}

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: HARMACEUTIC; v. 14, n. 1 JAN 2022.
• Citações Web of Science: 0

Resumo

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)

• Processo FAPESP: 15/09568-5 - Papel da autofagia no controle da infecção pelo Trypanosoma cruzi e a influência dos receptores da imunidade inata nesse processo
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