Cyclin D1 overexpression allows identification of an aggressive subset of leukemic lymphoproliferative disorder

The conjunction of clinical features, cell morphology and immunological cha racteristics allows an accurate diagnosis in most cases of B cell chronic l ymphoproliferative disorders (CLD). However, the diagnosis remains uncertai n in a small percentage of cases, often referred as to unclassified B cell proliferation or atypical chronic lymphocytic leukemia (CLL). We have studi ed retrospectively the 192 cases of leukemic CLD seen in our institution ov er a 3-year period, for which both clinical and routine biological data at presentation were available. Forty cases (20%) did not fit into any of the well-identified categories according to the FAB criteria and remained uncla ssified. We assessed cyclin D1 expression in all of these cases and found t hat 10 of them expressed a high level of cyclin D1 protein. We compared the characteristics of these 10 cases with those of the 30 cyclin D1 negative CLD. Despite non distinctive cytological and phenotypic features, the 10 cy clin Dt positive patients exhibited a strikingly uniform clinical presentat ion with elevated leukocytosis, massive spleen enlargement and no superfici al lymphadenopathy. Their outcome was very poor with a median survival of 1 0 months, contrasting with the prolonged survival of the cyclin Dt negative patients. The cytological features of tumor cells from these 10 patients w ith cyclin D1 positive unclassified leukemic CLD were similar to those of t he circulating lymphoid cells from 15 patients with histologically proven m antle cell lymphoma (MCL) and primary or secondary blood involvement. There fore, cyclin D1 expression allowed identification among the unclassified CL D, a subset of aggressive disorders which represent a leukemic counterpart of MCL (mantle cell leukemia). We suggest that determination of cyclin D1 e xpression by any technique available should be systematically included when investigating atypical CLL.