title: Clinicopathologic features of CDK6 translocation-associated B-cell lymphoproliferative disorders.
abstract: 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.
authors.affiliation: Division of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Dong
authors.initials: D
authors.lastname: Chen
authors.forename: Mark E
authors.initials: ME
authors.lastname: Law
authors.forename: Jason D
authors.initials: JD
authors.lastname: Theis
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Gamez
authors.forename: Lynn B
authors.initials: LB
authors.lastname: Caron
authors.forename: Julie A
authors.initials: JA
authors.lastname: Vrana
authors.forename: Ahmet
authors.initials: A
authors.lastname: Dogan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D018956:CD5 Antigens / Q000032:analysis; D056742:Cyclin D2; D051361:Cyclin-Dependent Kinase 6 / Q000032:analysis / Q000235:genetics*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000032:analysis; D019992:Databases as Topic; D005260:Female; D005838:Genotype; D006801:Humans; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis; D016393:Lymphoma, B-Cell / Q000201:enzymology / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000628:therapy; D008232:Lymphoproliferative Disorders / Q000201:enzymology / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D010766:Phosphorylation; D016160:Retinoblastoma Protein / Q000032:analysis; D014178:Translocation, Genetic; D016896:Treatment Outcome
chemical_list: C080336:CCND2 protein, human; D018956:CD5 Antigens; C436291:CDKN1B protein, human; D056742:Cyclin D2; D016213:Cyclins; D007145:Immunoglobulin kappa-Chains; D047908:Intracellular Signaling Peptides and Proteins; D016160:Retinoblastoma Protein; D050760:Cyclin-Dependent Kinase Inhibitor p27; C495911:CDK6 protein, human; D051361:Cyclin-Dependent Kinase 6