Blastoid Variants of Mantle Cell Lymphoma: Frequent bcl-1 Rearrangements at the Major Translocation Cluster Region and Tetraploid Chromosome Clones

Abstract

Sixty-four cases of mantle cell (centrocytic) non-Hodgkin's lymphomas have been analyzed for their cytomorphologic features, proliferation indices, bcl-1 rearrangements, p53 expression patterns, and DNA content by both interphase cytogenetic and DNA flow cytometric analyses. According to cytomorphology, three subtypes were recognized: a common, a lymphoblastoid, and a pleomorphic variant of mantle cell lymphoma (MCL). Blastoid MCL subtypes were characterized by distinctly elevated mitotic counts (57 and 51/10 HPF v 21/10 high-power fields in common MCL), proliferation indices (58% and 53% v 27% in common types, respectively; P < .001), frequent bcl-1 rearrangements at the major translocation cluster locus (59% v 40%), and overexpression of p53 (21% v 6%). However, the most interesting finding was a striking tendency of blastoid MCL subtypes to harbor chromosome numbers in the tetraploid range (36% of lymphoblastoid and 80% of pleomorphic types v 8% of common variants, P < .001), a feature clearly separating these neoplasms from other types of B-cell non-Hodgkin's lymphoma and possibly being related to cyclin D1 overexpression. Our data indicate that, although characterized by a uniform immunophenotype and common biologic background, MCL shows a broad spectrum of morphologic features ranging from small cell to blastoid types and that the morphologic spectrum is mirrored by distinct biologic features.

Delineation of distinct tumour profiles in mantle cell lymphoma by detailed cytogenetic, interphase genetic and morphological analysis

“…However, several additional chromosomal regions have been found to be altered in MCL, the molecular consequence of which has not been yet elucidated (Bea et al, 1999;Au et al, 2002;Salaverria et al, 2007). Of importance, the genetic constitution of bMCL and tetraploid MCL (tMCL) and their possible impact on the enhanced proliferation in these subtypes has not yet been fully characterized (Dreyling et al, 1997;Ott et al, 1997a;Au et al, 2002).…”

Antagonizing inactivated tumor suppressor genes and activated oncogenes by a versatile transgenesis system: application in mantle cell lymphoma

“…Key Words: functional genomics ⅐ RNA ⅐ transgenes ⅐ oncogenomics ⅐ genomic complementation ⅐ genetics of disease Mantle cell lymphoma (MCL) represents a non-Hodgkin lymphoma (NHL) (1), which is characterized by a block in differentiation, deregulation of cell proliferation as well as insufficient induction of apoptosis in B-cell lymphocytes (2,3). The characteristic translocation t(11;14)(q31;q32) results in a strong overexpression of the cyclin D1 gene (CCND1) (4).…”

“…While 1 Correspondence: Abteilung "Molekulare Genetik" (B060), Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. E-mail: m.macleod@dkfz.de 2 Conflict of Interest statement: The authors declare that they have no potential conflicts of interests. doi: 10.1096/fj.05-4854fje this expression is driven by ectopic gene promoters, reconstitution of gene defects regulated via endogenous promoters, enhancers, alternative transcription start sites, and splice variants of a specific gene is of distinct advantage (16) and was recently used to rescue phenotypes in RNAi-experiments (17).…”

Splenectomy in mantle cell lymphoma with leukaemia: a comparison with chronic lymphocytic leukaemia

“…Splenomegaly and peripheral blood lymphocytosis have been correlated with a bad prognosis and a shorter survival in MCL (Pittaluga et al, 1996;Argatoff et al, 1997;Ott et al, 1997;Bosch et al, 1998;Samaha et al, 1998;Hankin & Hunter, 1999). In the present study, despite the bad prognostic features of the patients with MCL who presented with splenomegaly and frank leukaemia, splenectomy enabled prolonged periods free from chemotherapy and a median post-splenectomy survival of 36 months.…”