Abl1-KO Mouse

Abl1, also known as Abelson murine leukemia viral oncogene homolog 1, is a key gene encoding a tyrosine kinase. It is involved in multiple cellular processes such as cell growth, differentiation, and adhesion through its participation in various signaling pathways [1-5].

In leukemia research, a translocation between chromosomes 9 and 22 leads to the formation of the constitutively active BCR-ABL1 oncoprotein, driving chronic myeloid leukemia (CML) [2-5]. Mutations in ABL1 kinase domain can confer resistance to ATP-competitive tyrosine kinase inhibitors (TKIs) used for CML treatment [1,2,3,4,5]. BCR-ABL1-like B-acute lymphoblastic leukemia/lymphoma, lacking the BCR-ABL1 translocation but having a similar gene expression pattern, may have alterations in the ABL class family of genes including ABL1, which determine sensitivity to tyrosine kinase inhibitors.

In conclusion, Abl1 is crucial for normal cellular functions through its kinase activity in signaling pathways. In the context of leukemia, understanding the role of Abl1, especially in the formation of BCR-ABL1 oncoprotein and associated drug resistance, has been significantly advanced through research. Insights from these studies have led to the development of targeted therapies like TKIs and investigational agents such as asciminib, aiming to improve treatment outcomes for leukemia patients [2-5].

References:

1. Réa, Delphine, Hughes, Timothy P. 2022. Development of asciminib, a novel allosteric inhibitor of BCR-ABL1. In Critical reviews in oncology/hematology, 171, 103580. doi:10.1016/j.critrevonc.2022.103580. https://pubmed.ncbi.nlm.nih.gov/35021069/

2. Leak, Steven, Horne, Gillian A, Copland, Mhairi. 2023. Targeting BCR-ABL1-positive leukaemias: a review article. In Cambridge prisms. Precision medicine, 1, e21. doi:10.1017/pcm.2023.9. https://pubmed.ncbi.nlm.nih.gov/38550948/

3. Manley, Paul W, Barys, Louise, Cowan-Jacob, Sandra W. 2020. The specificity of asciminib, a potential treatment for chronic myeloid leukemia, as a myristate-pocket binding ABL inhibitor and analysis of its interactions with mutant forms of BCR-ABL1 kinase. In Leukemia research, 98, 106458. doi:10.1016/j.leukres.2020.106458. https://pubmed.ncbi.nlm.nih.gov/33096322/

4. Amarante-Mendes, Gustavo P, Rana, Aamir, Datoguia, Tarcila Santos, Hamerschlak, Nelson, Brumatti, Gabriela. 2022. BCR-ABL1 Tyrosine Kinase Complex Signaling Transduction: Challenges to Overcome Resistance in Chronic Myeloid Leukemia. In Pharmaceutics, 14, . doi:10.3390/pharmaceutics14010215. https://pubmed.ncbi.nlm.nih.gov/35057108/

5. Branford, Susan, Fernandes, Adelina, Shahrin, NurHezrin, Shanmuganathan, Naranie, Wadham, Carol. . Beyond BCR::ABL1-The Role of Genomic Analyses in the Management of CML. In Journal of the National Comprehensive Cancer Network : JNCCN, 22, . doi:10.6004/jnccn.2023.7335. https://pubmed.ncbi.nlm.nih.gov/38394774/