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Updated: Jan 19, 2026

Tumor Engraftment in a Xenograft Mouse Model of Human Mantle Cell Lymphoma
10:52

Tumor Engraftment in a Xenograft Mouse Model of Human Mantle Cell Lymphoma

Published on: March 30, 2018

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Cutting Edge: ROR1/CD19 Receptor Complex Promotes Growth of Mantle Cell Lymphoma Cells Independently of the B Cell

Qian Zhang1, Hong Y Wang2, Xiaobin Liu2

  • 1Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104; Mariusz.Wasik@fccc.edu qian2@pennmedicine.upenn.edu.

Journal of Immunology (Baltimore, Md. : 1950)
|September 20, 2019
PubMed

Insights

Aberrant ROR1 expression drives mantle cell lymphoma (MCL) growth independently of BCR/BTK signaling. Targeting ROR1/CD19 offers a new strategy for MCL patients resistant to BTK inhibitors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Bruton tyrosine kinase (BTK) inhibitors show efficacy in mantle cell lymphoma (MCL).
  • Drug resistance to BTK inhibitors is a significant clinical challenge in MCL.
  • Aberrant signaling pathways can drive resistance to targeted therapies.

Purpose of the Study:

  • To investigate the role of receptor tyrosine kinase-like orphan receptor 1 (ROR1) in MCL.
  • To determine if ROR1 expression contributes to resistance against BTK inhibitors.
  • To explore ROR1/CD19 complex as a potential therapeutic target in MCL.

Main Methods:

  • Analysis of ROR1 expression in MCL patient samples.
  • Investigating the formation of ROR1/CD19 complexes.
  • Assessing the activation of PI3K-AKT and MEK-ERK signaling pathways.
  • Evaluating the impact of ROR1/CD19 on MCL cell growth.

Main Results:

  • Aberrant ROR1 expression was observed in a significant subset of MCL.
  • ROR1 forms a functional complex with CD19, activating PI3K-AKT and MEK-ERK pathways.
  • This ROR1/CD19 complex drives BCR/BTK-independent signaling and MCL cell growth.
  • ROR1/CD19 signaling effectively substitutes for BCR-BTK signaling in promoting MCL activation.

Conclusions:

  • ROR1 expression represents a novel mechanism of resistance to BTK inhibitors in MCL.
  • The ROR1/CD19 complex is a key driver of BCR/BTK-independent MCL progression.
  • Targeting ROR1 and/or CD19 presents a promising therapeutic strategy for ROR1-expressing MCL.

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