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

Leukemia. 1999 Sep;13(9):1343-51. doi: 10.1038/sj.leu.2401470.


The conjunction of clinical features, cell morphology and immunological characteristics allows an accurate diagnosis in most cases of B cell chronic lymphoproliferative disorders (CLD). However, the diagnosis remains uncertain in a small percentage of cases, often referred as to unclassified B cell proliferation or atypical chronic lymphocytic leukemia (CLL). We have studied retrospectively the 192 cases of leukemic CLD seen in our institution over 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 unclassified. We assessed cyclin D1 expression in all of these cases and found that 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 cyclin D1 positive patients exhibited a strikingly uniform clinical presentation with elevated leukocytosis, massive spleen enlargement and no superficial lymphadenopathy. Their outcome was very poor with a median survival of 10 months, contrasting with the prolonged survival of the cyclin D1 negative patients. The cytological features of tumor cells from these 10 patients with cyclin D1 positive unclassified leukemic CLD were similar to those of the circulating lymphoid cells from 15 patients with histologically proven mantle cell lymphoma (MCL) and primary or secondary blood involvement. Therefore, cyclin D1 expression allowed identification among the unclassified CLD, a subset of aggressive disorders which represent a leukemic counterpart of MCL (mantle cell leukemia). We suggest that determination of cyclin D1 expression by any technique available should be systematically included when investigating atypical CLL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cyclin D1 / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / physiology*
  • Humans
  • Leukemia, B-Cell / diagnosis
  • Leukemia, B-Cell / metabolism*
  • Leukemia, B-Cell / mortality
  • Male
  • Middle Aged
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Rate
  • Treatment Outcome


  • Cyclin D1