Wang, Li

Abstract Background: As a key receptor tyrosine kinase (RTK) regulating tumorigenesis, AXL is overexpressed in multiple different types of cancers. AXL can be activated by homodimerization after binding with its ligand, growth arrest specific 6 protein (Gas6) or by heterodimerization with other RTKs. AXL overexpression and/or activation have been reported to promote cancer cell proliferation, migration/invasion and to induce resistance to targeted therapy. However, the AXL downstream signaling network has not yet been fully elucidated. Methods: We employed a CRISPR-CAS9-based knockout technology to create AXL inducible knockout cells in a human triple negative breast cancer (TNBC) cell line, HCC1395. In order to explore the downstream signaling events driven by AXL, we induced AXL knockout for 72 hours and used a 6-plex TMT-labeling-based quantitative proteomic approach to characterize the protein phosphorylation alterations induced by AXL knockout. IMAC and anti-phosphotyrosine antibody (pY1000)-based phosphopeptide enrichment methods were used to comprehensively quantify the phosphoproteome changes induced by AXL knockout. Results: In this study, we identified 38,525 phospho serine/threonine sites and 1,427 phosphotyrosine sites. In response to AXL knockout, 1,581 phospho serine/threonine sites and 40 phosphotyrosine sites showed significant differences between AXL-KO and AXL-WT groups with >1.5-fold change and p<0.05 as the cutoff. Among them, 982 phosphoserine/threonine sites and 30 phosphotyrosine sites were decreased, while 599 phospho serine/threonine sites and 10 phosphotyrosine sites were increased in AXL-KO cells. Signaling pathway enrichment analysis revealed that suppressing AXL expression could inhibit multiple important cancer related signaling pathways, including cell cycle, focal adhesion, MAPK signaling pathway, p53 signaling pathway and mTOR signaling pathway. Conclusion: Quantitative analysis of the phosphoproteome driven by AXL demonstrated that AXL plays a pivotal role in regulating canonical oncogenic signaling but also signaling pathways involved in RNA processing and DNA repair. Our data also suggest that targeting AXL could suppress these oncogenic signaling pathways and have therapeutic potential to improve clinical outcomes for patients with AXL overexpression. Citation Format: Li Wang, Nicole Pearson, Yuning Xiong, Santosh Renuse, Ran Cheng, Jodi M. Carter, Akhilesh Pandey, Xinyan Wu. Quantitative phosphoproteomic analysis of AXL signaling network in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3913.

Abstract Introduction: Primary mucosa-associated lymphoid tissue (MALT) lymphomas originating in thymus is rare. And, there have been few reports of patients with MALT coexisting with amyloidosis. As far as we know, this was the first case report on MALT lymphoma associated with renal amyloidosis. Patient concerns: A 57-year-old man presented with nephrotic syndrome. Further workup revealed IgM-Lambda type monoclonal gammopathy. Bone marrow biopsy showed 8% clonal plasma cells. Renal biopsy confirmed the diagnosis of Lambda light chain AL amyloidosis. positron emission tomography/computed tomography showed thymic lesions which upon biopsy were diagnosed as MALT lymphoma of the thymus. Diagnosis: Primary thymic MALT lymphoma complicated with renal amyloidosis. Interventions: The patient underwent surgical resection of the thymus mass and 2 courses of chemotherapy. Outcomes: Follow-up data showed that the patient survived 18 months after surgical excision and chemotherapy. Conclusion: The case highlights the importance of screening for malignancy in patients with renal amyloidosis.