CXCR4, CXCR5 and CD44 May Be Involved in Homing of Lymphoma Cells into the Eye in a Patient Derived Xenograft Homing Mouse Model for Primary Vitreoretinal Lymphoma

Babst, Neele; Isbell, Lisa K; Rommel, Felix; Tura, Aysegül; Ranjbar, Mahdy; Grisanti, Salvatore; Tschuch, Cordula; Schueler, Julia; Doostkam, Soroush; Reinacher, Peter C.; Duyster, Justus; Kakkassery, Vinodh; Bubnoff, Nikolas von

doi:10.3390/ijms231911757

Cited by 4 publications

(2 citation statements)

References 68 publications

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“…Thus, we explored the regulation of CD44 expression by MyD88 L265P in more detail. Many previous studies reported an important functional role of CD44 in various types of cancer [ 48 , 49 , 50 , 51 , 52 , 53 , 54 ] and increased CD44 expression has also been observed in lymphoma [ 55 , 56 , 57 , 58 , 59 , 60 ]. Since we identified CD44 as a prominent downstream target of MyD88 L265P oncogenic NF-κB signaling, we wondered whether CD44 might serve as a cell surface marker of MyD88 L265P -dependent DLBCL lymphoma.…”

Section: Resultsmentioning

confidence: 99%

Transcriptome Analysis of Diffuse Large B-Cell Lymphoma Cells Inducibly Expressing MyD88 L265P Mutation Identifies Upregulated CD44, LGALS3, NFKBIZ, and BATF as Downstream Targets of Oncogenic NF-κB Signaling

Turi

Sithara

Hofmanová

et al. 2023

IJMS

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During innate immune responses, myeloid differentiation primary response 88 (MyD88) functions as a critical signaling adaptor protein integrating stimuli from toll-like receptors (TLR) and the interleukin-1 receptor (IL-1R) family and translates them into specific cellular outcomes. In B cells, somatic mutations in MyD88 trigger oncogenic NF-κB signaling independent of receptor stimulation, which leads to the development of B-cell malignancies. However, the exact molecular mechanisms and downstream signaling targets remain unresolved. We established an inducible system to introduce MyD88 to lymphoma cell lines and performed transcriptomic analysis (RNA-seq) to identify genes differentially expressed by MyD88 bearing the L265P oncogenic mutation. We show that MyD88L265P activates NF-κB signaling and upregulates genes that might contribute to lymphomagenesis, including CD44, LGALS3 (coding Galectin-3), NFKBIZ (coding IkBƺ), and BATF. Moreover, we demonstrate that CD44 can serve as a marker of the activated B-cell (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) and that CD44 expression is correlated with overall survival in DLBCL patients. Our results shed new light on the downstream outcomes of MyD88L265P oncogenic signaling that might be involved in cellular transformation and provide novel therapeutical targets.

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Section: Resultsmentioning

confidence: 99%

Transcriptome Analysis of Diffuse Large B-Cell Lymphoma Cells Inducibly Expressing MyD88 L265P Mutation Identifies Upregulated CD44, LGALS3, NFKBIZ, and BATF as Downstream Targets of Oncogenic NF-κB Signaling

Turi

Sithara

Hofmanová

et al. 2023

IJMS

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“…PCNSL xenografted mice. PVRL lymphoma cells in this model expressed chemokine receptors CXCR4 and CXCR5 as well as CD44 [45].…”

Section: Discussionmentioning

confidence: 99%

Patient‐derived xenograft mouse models to investigate tropism to the central nervous system and retina of primary and secondary central nervous system lymphoma

Isbell

Tschuch

Doostkam

et al. 2023

Neuropathology Appl Neurobio

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Aims How and why lymphoma cells home to the central nervous system and vitreoretinal compartment in primary diffuse large B‐cell lymphoma of the central nervous system remain unknown. Our aim was to create an in vivo model to study lymphoma cell tropism to the central nervous system. Methods We established a patient‐derived central nervous system lymphoma xenograft mouse model and characterised xenografts derived from four primary and four secondary central nervous system lymphoma patients using immunohistochemistry, flow cytometry and nucleic acid sequencing technology. In reimplantation experiments, we analysed dissemination patterns of orthotopic and heterotopic xenografts and performed RNA sequencing of different involved organs to detect differences at the transcriptome level. Results We found that xenografted primary central nervous system lymphoma cells home to the central nervous system and eye after intrasplenic transplantation, mimicking central nervous system and primary vitreoretinal lymphoma pathology, respectively. Transcriptomic analysis revealed distinct signatures for lymphoma cells in the brain in comparison to the spleen as well as a small overlap of commonly regulated genes in both primary and secondary central nervous system lymphoma. Conclusion This in vivo tumour model preserves key features of primary and secondary central nervous system lymphoma and can be used to explore critical pathways for the central nervous system and retinal tropism with the goal to find new targets for novel therapeutic approaches.

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Role and application of chemokine CXCL13 in central nervous system lymphoma

Li,

Zhang,

Jin

et al. 2023

Ann Hematol

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CXCR4, CXCR5 and CD44 May Be Involved in Homing of Lymphoma Cells into the Eye in a Patient Derived Xenograft Homing Mouse Model for Primary Vitreoretinal Lymphoma

Cited by 4 publications

References 68 publications

Transcriptome Analysis of Diffuse Large B-Cell Lymphoma Cells Inducibly Expressing MyD88 L265P Mutation Identifies Upregulated CD44, LGALS3, NFKBIZ, and BATF as Downstream Targets of Oncogenic NF-κB Signaling

Transcriptome Analysis of Diffuse Large B-Cell Lymphoma Cells Inducibly Expressing MyD88 L265P Mutation Identifies Upregulated CD44, LGALS3, NFKBIZ, and BATF as Downstream Targets of Oncogenic NF-κB Signaling

Patient‐derived xenograft mouse models to investigate tropism to the central nervous system and retina of primary and secondary central nervous system lymphoma

Role and application of chemokine CXCL13 in central nervous system lymphoma

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