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Published on: December 4, 2018
Identification of Annexin A1 interacting proteins in chronic myeloid leukemia KCL22 cells
Irene Colavita1, Nicola Esposito, Concetta Quintarelli
1CEINGE-Biotecnologie Avanzate scarl, Napoli, Italy.
Abstract:
In the present study, we used a functional proteomic approach to identify Annexin A1 (Anxa1) interacting proteins in the Philadelphia-positive KCL22 cell line. We focused on Anxa1 because it is one of the major proteins upregulated in imatinib-sensitive KCL22S cells versus imatinib-resistant KCL22R. Our proteomic strategy revealed 21 interactors. Bioinformatic analysis showed that most of these proteins are involved in cell death processes. Among the proteins identified, we studied the interaction of Anxa1 with two phosphatases, Shp1 and Shp2, which were recently identified as biomarkers of imatinib sensitivity in patients affected by chronic myeloid leukemia. Our data open new perspectives in the search for annexin-mediated signaling pathways and may shed light on mechanisms of resistance to imatinib that are unrelated to Bcr-Abl activity. All mass spectrometry data have been deposited in the ProteomeXchange with identifier PXD000030.
Insights
Researchers identified proteins interacting with Annexin A1 (Anxa1) in leukemia cells, revealing potential new signaling pathways. This discovery may explain imatinib resistance mechanisms not linked to Bcr-Abl activity.
Area of Science:
- Proteomics
- Cell Biology
- Biochemistry
Background:
- Annexin A1 (Anxa1) is upregulated in imatinib-sensitive KCL22S cells compared to resistant KCL22R cells.
- Understanding Anxa1 interactions is crucial for deciphering imatinib sensitivity and resistance.
- Chronic myeloid leukemia (CML) treatment resistance remains a significant clinical challenge.
Purpose of the Study:
- To identify Annexin A1 (Anxa1) interacting proteins in Philadelphia-chromosome-positive KCL22 cells using a functional proteomic approach.
- To investigate the role of Anxa1 in signaling pathways relevant to imatinib sensitivity and resistance.
- To explore potential biomarkers for imatinib sensitivity beyond Bcr-Abl.
Main Methods:
- Functional proteomic analysis of KCL22 cell line.
- Mass spectrometry to identify Anxa1 interactors.
- Bioinformatic analysis of identified proteins.
- Focused study on Anxa1 interactions with Shp1 and Shp2 phosphatases.
Main Results:
- Identified 21 proteins interacting with Annexin A1 (Anxa1).
- Bioinformatic analysis indicated involvement of interactors in cell death pathways.
- Confirmed interactions between Anxa1 and phosphatases Shp1 and Shp2.
- Shp1 and Shp2 are potential biomarkers for imatinib sensitivity in CML.
Conclusions:
- The study identified novel Anxa1-interacting proteins, expanding knowledge of annexin-mediated signaling.
- Findings suggest potential mechanisms of imatinib resistance independent of Bcr-Abl activity.
- Anxa1 and its interactors, like Shp1 and Shp2, offer new avenues for understanding and potentially overcoming CML treatment resistance.
