Clonality Assessment in Blood of Patients with Mantle Cell Lymphoma

Abstract

The presence of circulating neoplastic cells at diagnosis was assessed in the blood of patients presenting with mantle cell lymphoma (MCL) to determine the feasibility of a diagnostic molecular assay. Blood samples from 16 patients with pathologically reviewed MCL were analysed for the t(11;14)(q13;q32) translocation by the polymerase chain reaction (PCR): 7 (44%) were found positive. The remaining cases were examined by PCR for the presence of circulating neoplastic B-cells by amplifying the third complementarity region (CDR3) of immunoglobulin heavy chain genes and the immunoglobulin light kappa chain deletion rearrangements. A further 7 (44%) patients showed the presence of clonal lymphoma cells, leaving only 2 (12%) of cases negative for circulating lymphomatous cells. This study suggests that there is a high incidence of lymphoma cells in the blood of patients presenting with MCL. PCR for these clonal cells may be diagnostically useful.

Molecular basis of mantle cell lymphoma

“…The rearranged VDJ segment is almost unique for each B‐cell clone, and it is therefore a potential marker of clonality in MCL (Kurokawa et al , 1997; Bertoni et al , 1999a; Pittaluga et al , 1999; Hoeve et al , 2000; Theriault et al , 2000). PCR analysis with consensus upper primers specific for the highly conserved framework region 3 (FR3A) at the 3′‐end of the VH segment and consensus lower primers to the JH is the most commonly used.…”

“…In the t(11;14)(q13;q32) translocation, present virtually in all cases of MCL (Leroux et al , 1991; Rimokh et al , 1994; Zucca et al , 1995; Dreyling et al , 1997; Ott et al , 1997a; Chibbar et al , 1998; Fan et al , 1998; Bertoni et al , 1999a; Li et al , 1999; Stamatopoulos et al , 1999; Katz et al , 2000; Welzel et al , 2001; Belaud‐Rotureau et al , 2002), the cyclin D1 gene, on 11q13, is juxtaposed to the IgH ‘Joining’ (J) region, on 14q32 (Fig 1). The t(11;14) determines the ectopic and deregulated expression of cyclin D1 in lymphoid cells, due to the juxtaposition of the gene to the strong B‐cell IgH transcription enhancers.…”

Identification of novel regions of amplification and deletion within mantle cell lymphoma DNA by comparative genomic hybridization

“…Patients usually present with extensive disease, B symptoms, extranodal involvement and splenomegaly (Vandenberghe et al , 1991; Pittaluga et al , 1995; Zucca et al , 1995). Frequently there is peripheral blood involvement (Deoliveira et al , 1989; Raffeld & Jaffe, 1991; Bertoni et al , 1999) and this has been associated with shortened survival.…”