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Cyclin D1-negative mantle cell lymphoma: a clinicopathologic study based on gene expression profiling
Kai Fu1, Dennis D Weisenburger, Timothy C Greiner
1Department of Pathology and Microbiology, University of Nebraska Medical Center, 983135 Nebraska Medical Center, Omaha, NE 68198-3135, USA. kfu@unmc.edu
Blood
|August 27, 2005
Summary
Cyclin D1-negative mantle cell lymphoma (MCL) cases exist, characterized by cyclin D2 or D3 expression instead of cyclin D1. These cases share clinical and genetic similarities with typical MCL, expanding the disease spectrum.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- Cyclin D1 overexpression is considered crucial in mantle cell lymphoma (MCL) pathogenesis.
- The existence of cyclin D1-negative MCL has been debated due to diagnostic challenges.
Purpose of the Study:
- To investigate the clinical, pathological, and genetic characteristics of cyclin D1-negative MCL.
- To determine if alternative D-type cyclins are involved in cyclin D1-negative MCL.
Main Methods:
- Gene expression profiling to identify MCL cases lacking cyclin D1.
- Fluorescence in situ hybridization (FISH) to analyze chromosomal translocations and gene loci.
- Protein and mRNA expression analysis of D-type cyclins.
Main Results:
- Six cases of cyclin D1-negative MCL were identified, exhibiting characteristic MCL morphology and gene expression signatures.
- These cases lacked the t(11;14) translocation but showed cyclin D2 (2 cases) or cyclin D3 (4 cases) expression.
- No chromosomal translocations or amplifications involving CCND2 and CCND3 were detected.
Conclusions:
- Cyclin D1-negative MCL is a distinct entity within the MCL spectrum.
- Upregulation of cyclin D2 or cyclin D3 can potentially substitute for cyclin D1 in MCL pathogenesis.
- Clinical presentation of cyclin D1-negative MCL is similar to cyclin D1-positive MCL.