Cyclin D2 is overexpressed in proliferation centers of CLL/SLL

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BlankCyclin D2 is overexpressed in proliferation centers of chronic lymphocytic

leukemia/small lymphocytic lymphoma.

T Igawa, Y Sato, K Takata, S Fushimi, M Tamura, N Nakamura, Y Maeda, Y Orita, M

Tanimoto, and T Yoshino

Cancer Sci, July 25, 2011; .

Department of Pathology, Okayama University Graduate School of Medicine,

Dentistry and Pharmaceutical Sciences, Okayama, Japan Department of Pathology

and Experimental Medicine, Graduate School of Medicine, Dentistry and

Pharmaceutical Sciences, Okayama University, Japan Department of Pathology,

Tokai University School of Medicine, Japan Department of Hematology and

Oncology, Okayama University Graduate School of Medicine, Dentistry and

Pharmaceutical Sciences, Japan Department of Otolaryngology-Head and Neck

Surgery, Okayama University Graduate School of Medicine, Dentistry and

Pharmaceutical Sciences, Japan.

D cyclins are important cell-cycle regulatory proteins involved in the

pathogenesis of some lymphomas. Cyclin D1 overexpression is a hallmark of mantle

cell lymphoma, whereas cyclins D2 and D3 have not been shown to be closely

associated with any particular subtype of lymphoma. In the present study, we

found that cyclin D2 was specifically overexpressed in the proliferation centers

(PCs) of all examined cases of chronic lymphocytic leukemia/small lymphocytic

lymphoma (CLL/SLL) (19/19). To examine the molecular mechanisms underlying this

overexpression, we immunohistochemically examined nuclear factor (NF)-?B, p15,

p16, p18, and p27 expression in the PCs of 6 patients. Five cases showed the

upregulation of NF-?B, which is known to directly induce cyclin D2 by binding to

the promoter region of CCND2. All 6 examined PCs demonstrated p27

downregulation; in contrast, p15 upregulation was detected in 5 out of 6

examined PCs. This discrepancy suggests that unknown cell-cycle regulatory

mechanisms involving NF-?B-related pathways are also involved, because NF-?B

upregulates cyclin D2 not only directly but also through c-Myc, which is

believed to downregulate both p27 and p15. In conclusion, cyclin D2 is

overexpressed in the PCs of CLL/SLL, and this overexpression is partly due to

the upregulation of NF-?B-related pathways.

PMID: 21790895