Clinical and biological features of B‐cell neoplasms with CDK6 translocations: an association with a subgroup of splenic marginal zone lymphomas displaying frequent CD5 expression, prolymphocytic cells, and TP53 abnormalities

• Published in: British journal of haematology Vol. 193; no. 1; pp. 72 - 82
• Main Authors: Gailllard, Baptiste, Cornillet‐Lefebvre, Pascale, Le, Quoc‐Hung, Maloum, Karim, Pannetier, Mélanie, Lecoq‐Lafon, Carinne, Grange, Béatrice, Jondreville, Ludovic, Michaux, Lucienne, Nadal, Nathalie, Ittel, Antoine, Luquet, Isabelle, Struski, Stéphanie, Lefebvre, Christine, Gaillard, Jean‐Baptiste, Lafage‐Pochitaloff, Marina, Balducci, Estelle, Penther, Dominique, Barin, Carole, Collonge‐Rame, Marie Agnès, Jimenez‐Poquet, Mélanie, Richebourg, Steven, Lemaire, Pierre, Defasque, Sabine, Radford‐Weiss, Isabelle, Bidet, Audrey, Susin, Santos A., Nguyen‐Khac, Florence, Chapiro, Elise
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.04.2021; Wiley
• Subjects: Bronchus; CD5; CD5 antigen; CDK6; Chronic lymphocytic leukemia; Gene deletion; Heavy chains; Hematology; Human health and pathology; Hybridization; Immunoglobulins; Leukemia; Life Sciences; Lymphocytosis; Lymphoid tissue; Lymphoma; marginal zone lymphoma; Neoplasia; Notch protein; Notch2 protein; p53 Protein; prolymphocytic cell; Spleen; TP53; Translocation; Tumors; CDK6; prolymphocytic cell; CD5; TP53; marginal zone lymphoma
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/bjh.17141

Summary A translocation involving the cyclin‐dependent kinase 6 (CDK6) gene [t(CDK6)] is a rare but recurrent abnormality in B‐cell neoplasms. To further characterise this aberration, we studied 57 cases; the largest series reported to date. Fluorescence in situ hybridisation analysis confirmed the involvement of CDK6 in all cases, including t(2;7)(p11;q21) immunoglobulin kappa locus (IGK)/CDK6 (n = 51), t(7;14)(q21;q32) CDK6/immunoglobulin heavy locus (IGH) (n = 2) and the previously undescribed t(7;14)(q21;q11) CDK6/T‐cell receptor alpha locus (TRA)/T‐cell receptor delta locus (TRD) (n = 4). In total, 10 patients were diagnosed with chronic lymphocytic leukaemia, monoclonal B‐cell lymphocytosis or small lymphocytic lymphoma, and 47 had small B‐cell lymphoma (SmBL) including 36 cases of marginal zone lymphoma (MZL; 34 splenic MZLs, one nodal MZL and one bronchus‐associated lymphoid tissue lymphoma). In all, 18 of the 26 cytologically reviewed cases of MZL (69%) had an atypical aspect with prolymphocytic cells. Among the 47 patients with MZL/SmBL, CD5 expression was found in 26 (55%) and the tumour protein p53 (TP53) deletion in 22 (47%). The TP53 gene was mutated in 10/30 (33%); the 7q deletion was detected in only one case, and no Notch receptor 2 (NOTCH2) mutations were found. Immunoglobulin heavy‐chain variable‐region (IGHV) locus sequencing revealed that none harboured an IGHV1‐02*04 gene. Overall survival was 82% at 10 years and not influenced by TP53 aberration. Our present findings suggest that most t(CDK6)+ neoplasms correspond to a particular subgroup of indolent marginal zone B‐cell lymphomas with distinctive features.