# Development of Mantle Cell Lymphoma Proliferation Signature Assay

> **NIH NIH UH3** · MAYO CLINIC ARIZONA · 2020 · $344,075

## Abstract

PROJECT SUMMARY/ABSTRACT
This proposal, “Assay Development of the MCL35 for Mantle Cell Lymphoma (MCL),” is written to validate a
prognostic assay for MCL based on quantification of a proliferation signature using digital gene expression
analysis. MCL is a B cell malignancy with a broad spectrum of clinical, pathological and biological features.
MCL is defined by the t(11;14)(q13;q32) translocation, which results in over expression of the cyclin D1 protein
and cell cycle dysregulation. MCL cases have markedly variable clinical behavior ranging from indolent to
highly aggressive disease, with treatment options ranging from watchful waiting to high dose chemotherapy
and stem cell transplant. The current approach to treatment is based largely on the patient's age at diagnosis
and currently there is no therapeutic standard. Previously, our research consortium, the Lymphoma and
Leukemia Molecular Profiling Project (LLMPP) analyzed snap frozen MCL tissue biopsies using gene
expression profiling (GEP) and identified a “Proliferation Signature” as the most powerful biomarker correlating
with patient survival in MCL. However, the original techniques using frozen tissues and GEP were impractical
for routine diagnostics. A potentially easy solution has been to use immunohistochemistry on tissue biopsies to
assess the presence of the Ki67 antigen as a global marker of cell proliferation. Ki67 studies have been
prognostic in multiple studies using various thresholds; however, there are serious issues with reproducibility
between different lab techniques and Pathologists' approach to interpretation. Therefore, as part of our work in
the National Cancer Institute's SPECSII program, we developed a novel GEP proliferation signature assay for
MCL that works well in formalin-fixed, paraffin-embedded tissues (FFPET) called the “MCL35”. The MCL35
uses the clinical-grade NanoString nCounter system, which is FDA-approved as the technical platform for the
ProSigna Breast Cancer assay. The MCL35 is accurate, reproducible, with an inter-lab reproducibility of 100%
in our initial work, making it a strong candidate for application in the clinical diagnostic setting. The MCL35
assay has gained attention since first being orally presented at the American Society of Clinical Oncology in
June 2016, and we are in discussions with pharmaceutical companies and clinical trial cooperative groups on
applications for the assay. The goals of the current project are first to thoroughly analytically validate the
MCL35 (UH2 phase); then, use the refined assay to retrospectively interrogate clinical trial cohorts to establish
it's clinical validity (UH3 phase). The long term goal is to use the resulting refined and validated MCL35 to
prospectively identify those MCL patients in need of immediate curative intent therapy in order to design
clinical trials around this high risk subset and improve patient survival.

## Key facts

- **NIH application ID:** 9993385
- **Project number:** 5UH3CA217847-04
- **Recipient organization:** MAYO CLINIC ARIZONA
- **Principal Investigator:** Lisa Rimsza
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $344,075
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9993385

## Citation

> US National Institutes of Health, RePORTER application 9993385, Development of Mantle Cell Lymphoma Proliferation Signature Assay (5UH3CA217847-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9993385. Licensed CC0.

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