Related Experiment Video

Updated: Jul 13, 2025

Establishment of a Human Multiple Myeloma Xenograft Model in the Chicken to Study Tumor Growth, Invasion and Angiogenesis
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Establishment of a Human Multiple Myeloma Xenograft Model in the Chicken to Study Tumor Growth, Invasion and Angiogenesis

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The Potential of JAG Ligands as Therapeutic Targets and Predictive Biomarkers in Multiple Myeloma

Natalia Platonova1, Elisa Lazzari1,2,3, Michela Colombo1

  • 1Department of Health Sciences, Università degli Studi di Milano, 20142 Milan, Italy.

International Journal of Molecular Sciences
|October 14, 2023
PubMed

Insights

Targeting JAG1 and JAG2 ligands may treat multiple myeloma (MM). Silencing these ligands reduced tumor burden in models and JAG2 expression predicts patient survival, supporting JAG1/2-tailored therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • NOTCH ligands JAG1 and JAG2 are implicated in multiple myeloma (MM) cell proliferation, drug resistance, and tumor microenvironment interactions.
  • These interactions include promoting angiogenesis and osteoclastogenesis, suggesting JAG ligands as potential therapeutic targets.

Purpose of the Study:

  • To investigate the functional role of JAG1 and JAG2 in a multiple myeloma (MM) in vivo model and primary patient samples.
  • To evaluate JAG1 and JAG2 as potential therapeutic targets and biomarkers in MM.

Main Methods:

  • Conditional silencing of JAG1/2 in a MM xenograft mouse model.
  • Analysis of JAG1 and JAG2 protein expression in MM cell lines and patient bone marrow biopsies.
  • Utilizing the MMRF CoMMpass dataset to assess JAG2 gene expression as a predictive biomarker.

Main Results:

  • JAG1 and JAG2 protein expression is common in MM cell lines.
  • Silencing JAG1 and JAG2 led to a reduction in tumor burden in the MM xenograft model.
  • JAG1 and JAG2 protein levels correlated with MM cell presence in patient bone marrow.
  • JAG2 gene expression was a significant predictor of overall and progression-free survival in MM patients.

Conclusions:

  • JAG1 and JAG2 show potential as therapeutic targets for multiple myeloma (MM).
  • JAG2 gene expression serves as a predictive biomarker for patient survival in MM.
  • These findings support the development of JAG1/2-targeted therapies and the clinical utility of JAG2 as a biomarker.
Keywords:
JAG1JAG2NOTCH signalingmicroenvironmentmouse modelmultiple myelomaproliferation

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