CCMCL 1: A New Model of Aggressive Mantle Cell Lymphoma

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Eric Hsi, MD

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Jason Ospina, PhD

What is it? What does it do?

Mantle cell lymphoma (MCL) is incurable using current standard therapeutic regimens.  Additionally, there are relatively few cell lines and mouse models to support drug discovery and development efforts. Currently available fully human MCL lines have not been well characterized at the molecular level, nor have they been compared with primary tumor cells. Dr. Hsi and colleagues at Cleveland Clinic have developed CCMCL1, a new well-characterized, aggressive MCL cell line.  CCMCL1 has the IGH-CCND1 genetic hallmark of MCL and closely resembles the terminal-phase leukemic MCL cells as evidenced by immunophenotyping, karyotyping, IGHV sequence, and WES.  Additionally primary cells harbor a MYC translocation, a known albeit unusual abnormality in MCL progression, typically seen in blastoid MCL.

Why is it better?

WES provides unbiased, direct evidence for conservation of the MCL genome in CCMCL1 at single-nucleotide resolution. WES detected no mutation in genes of the B-cell receptor or phosphatidylinositol 3-kinase pathway, including BTK and AKT. However, CCMCL1 constitutively expressed phosphorylated AKT and BTK, suggesting CCMCL1 is an appropriate model for investigating therapeutic targeting of these two pathways in MCL.

Other MCL cell lines have mutations or deletions in either ATM or TP53; with this respect CCMCL1 also offers an opportunity for MCL studies without the interference of ATM or TP53 loss.

What is its current status?

Clinically active agents ibrutinib and bortezomib have been tested in our cell line and results support the clinical relevance or our MCL model.

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