Clinicopathologic features of CDK6 translocation-associated B-cell lymphoproliferative disorders

Dong Chen, Mark E. Law, Jason D. Theis, Jeffrey D. Gamez, Lynn B. Caron, Julie A. Vrana, Ahmet Dogan

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Cyclin-dependent protein kinase 6 (CDK6), in cooperation with cyclin Ds, drives cell cycle progression from G1 to S phase through phosphorylation and subsequent inactivation of retinoblastoma 1 protein. Alteration of this pathway results in both nonhematologic and hematologic malignancies, which include a small subset of B-cell lymphoproliferative disorders (BLPDs). We identified 5 cases of BLPD that carried CDK6 chromosomal translocations and characterized their clinical, pathologic, immunophenotypic, and genetic features. Common clinical characteristics included marked neoplastic lymphocytosis, systemic lymphadenopathy, splenomegaly, and bone marrow involvement. Three patients were diagnosed with low-grade B-cell lymphoma and had an indolent clinical course, and 2 patients (one who transformed to large B-cell lymphoma, and the other who was initially diagnosed with a high-grade B-cell lymphoma) had an aggressive clinical course. Immunophenotypically, the neoplastic B cells expressed CD5, CDK6, and cytoplasmic retinoblastoma 1 protein in all cases, expressed phospho-RB, p27kip1, and cyclin D2 in most cases, and uniformly lacked expression of all other cyclins. In 4 cases, the CDK6 translocation partner was kappa immunoglobulin light-chain gene; and in the fifth case, the CDK6 translocation partner was unknown. These distinct clinicopathologic and cytogenetic features distinguish the CDK6 translocation-associated BLPDs (CDK6-BLPDs) from other mature B-cell lymphomas.

Original languageEnglish (US)
Pages (from-to)720-729
Number of pages10
JournalAmerican Journal of Surgical Pathology
Issue number5
StatePublished - May 2009


  • Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)
  • Cyclin D
  • Cyclin-dependent protein kinase (CDK)
  • Mantle cell lymphoma (MCL)
  • Retinoblastoma protein (Rb)
  • Splenic marginal zone lymphoma (SMZL)

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine


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