Blastoid and common variants of mantle cell lymphoma exhibit distinct immunophenotypic and interphase FISH features

Parrens, Marie; Belaud-Rotureau, M.-A.; Fitoussi, Olivier; Carerre, N.; Bouabdallah, Kamal; Marit, Gérald; Dubus, Pierre; Mascarel, A. De; Merlio, Jean-Philippe

doi:10.1111/j.1365-2559.2005.02323.x

Cited by 30 publications

(14 citation statements)

References 34 publications

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“…Sequence analysis of the VDJ regions of the rearranged IgH allele proved clonal identity in each set of paired samples in all five patients. These results support the concept that blastoid MCL arising in patients with typical MCL represents histologically detectable transformation of the original neoplastic clone [16].…”

Section: Discussionsupporting

confidence: 71%

Immunophenotypic profile and clinical characteristics in patients with advanced stage mantle cell lymphoma

Todorović¹,

Pavlović

Balint

et al. 2007

Med Oncol

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The objective of this study was to evaluate immunophenotypic profile along with clinical follow-up in patients with advanced stage mantle cell lymphoma (MCL), and their possible influence on overall survival (OS). Bone marrow (BM) cell and/or peripheral blood mononuclear cell flow cytometric analyses of the following antigens were performed: HLA-DR, CD19, CD20, CD22, CD23, CD25, CD10, SmIg, kappa, lambda, CD79b, CD38, FMC7, CD3, CD2, and CD5. There were 14 patients in IV CS, and 26 patients in CS V. All patients were treated with CHOP. Immunological markers showed a typical phenotype (CD5+ CD23-, Cyclin D1) in all cases. Pathohistological type of BM infiltration was predominantly diffuse (72.5%), and in remainder of patients, nodular. Comparison of patients with leukemic phase of MCL with CSIV (BM), has shown significantly higher expression of CD19, CD20, and CD23, followed by permanently negative expression of CD23. Patients with blastic variant of MCL had higher expression of CD23, compared to typical MCL (P < 0.001). Median OS was 20 months, and there were no significant OS-differences between CS IV and leukemic phase patients. Survival analyses showed that negative prognostic influence had high IPI (P < 0.01), presence of extranodal localization (P < 0.01), and diffuse type of BM involvement (P < 0.01). Using Cox regression according to OS, IPI had independent prognostic value (P < 0.001). Our results demonstrated that in the advanced MCL patients the most powerful prognostic factor was IPI, while extranodal localization and type of BM infiltration were of a limited value.

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Section: Discussionsupporting

confidence: 71%

Immunophenotypic profile and clinical characteristics in patients with advanced stage mantle cell lymphoma

Todorović¹,

Pavlović

Balint

et al. 2007

Med Oncol

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“…Three more samples had a distal UTR/proximal UTR ratio ranging from 0.73 to 0.83; one scenario that may explain these intermediate ratios is amplification of the CCND1 locus with deletion in the 3ЈUTR region in one amplified copy of the gene, as described previously. 24 In summary, all 7 cases had distal UTR/proximal UTR ratios below the 5th percentile (0.93) of the normal data and are therefore considered to have a genomic deletion (P Ͻ .001). Interestingly, no genomic deletions were detected by qPCR in 7 cases expressing truncated cyclin D1a mRNA, implying that other molecular mechanisms were responsible for the aberrant cyclin D1a transcripts in these cases.…”

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confidence: 99%

Point mutations and genomic deletions in CCND1 create stable truncated cyclin D1 mRNAs that are associated with increased proliferation rate and shorter survival

Wiestner

Tehrani

Chiorazzi

et al. 2007

Blood

220

172

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A gene expression signature of tumor proliferation rate in mantle cell lymphoma (MCL) is an overriding molecular predictor of the length of survival following diagnosis. Many strongly proliferative MCL tumors have exceptionally high cyclin D1 mRNA levels and preferentially express short cyclin D1 mRNA isoforms. We demonstrate here that these short mRNAs are cyclin D1a isoforms with truncated 3UTRs, not alternatively spliced cyclin D1b mRNA isoforms. Among 15 MCL tumors with truncated cyclin D1 mRNAs, 7 had genomic deletions in the CCND1 3UTR region. In 3 others, CCND1 contained point mutations that created premature polyadenylation signals, giving rise to 1.5-kb mRNAs lacking most of the 3UTR. Both types of genomic alteration created transcripts lacking mRNA destabilization elements present in the wild-type cyclin D1a mRNA. Premature polyadenylation due to a 3UTR mutation also was present in the Z-138 MCL cell line, which expressed both truncated and full-length cyclin D1a mRNAs. In these cells, the half-life of the short cyclin D1a mRNA was much longer than that of the full-length mRNA. We conclude that alterations of CCND1 3UTR IntroductionMantle cell lymphoma (MCL) comprises about 6% of all nonHodgkin lymphoma and is considered incurable with standard chemotherapy. 1,2 Median survival is approximately 3 years, but survival ranges from less than one year to Ͼ 6 years. The hallmark genetic feature of MCL is the t(11;14) translocation that leads to misexpression of cyclin D1 in the malignant cells. [3][4][5] The t(11;14) is not unique to MCL and occurs also in multiple myeloma. 6 Cyclin D1 is a member of the D-type cyclins that regulate the transition from G 0 /G 1 phase to S phase of the cell cycle. 7 Cyclin D1 is not normally expressed at high levels in lymphoid cells, and its expression from the t(11;14) translocated allele is driven by enhancer elements in the immunoglobulin heavy chain locus. Most t(11;14) translocations take place at the 5Ј end of the cyclin D1 locus, but translocations at the 3Јend of the gene also have been described in some cases. 8 CCND1 has 5 exons, which can be alternatively spliced to create 2 major isoforms, cyclin D1a and D1b. The cyclin D1a isoform is 4.5 kb in length, with a coding region of only 882 bp. The majority of this mRNA consists of 3ЈUTR sequences containing mRNA destabilizing elements. The cyclin D1b isoform lacks exon 5 but retains intron 4, which contains a translation stop codon after 99 bp and a polyadenylation signal less then 300 bp 3Ј from this stop codon. The 1.7-kb cyclin D1b mRNA is found in most tumors and cell lines that express cyclin D1 and encodes a 274 amino acid protein that differs at the C terminus from the 294 amino acid protein encoded by the cyclin D1a mRNA. [9][10][11][12][13] In contrast to cyclin D1a, cyclin D1b is potently transforming in experimental models. 13,14 The relative abundance of the cyclin D1b isoform is reportedly affected by a G/A single nucleotide polymorphism at the last base of exon 4 (position 870, codon 241), which is the...

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“…1 The blastoid and pleomorphic types are morphological variants of MCL, and their recognition is of clinical significance as they are associated with a worse clinical outcome. 2,12 The immunophenotype of MCL lymphoma is unique and consists of CD20 + , CD5 + , cyclin D1 + , CD23 2 , and CD10 2 . BV-MCL has a higher proliferation rate compared with the usual MCL.…”

Section: Discussionmentioning

confidence: 99%

“…3), a complex genetic profile typically seen in the blastoid variant of MCL. 12 Biochemical and hematological tests were normal, and computed tomography scans of the head and neck, thorax, abdomen, and pelvis were unremarkable. A bilateral bone marrow biopsy revealed normal findings with no infiltration by lymphoma.…”

Section: Case Report Pathological and Fluorescence In Situ Hybridizamentioning

confidence: 96%

Primary Cutaneous Blastoid Mantle Cell Lymphoma-Case Report

Estrozi

Sanches²,

Varela³

et al. 2009

The American Journal of Dermatopathology

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Mantle cell lymphoma (MCL) commonly involves extranodal sites, usually as a manifestation of disseminated disease. In rare cases, MCLs may arise as a primary tumor in the skin. Blastoid mantle cell lymphoma (BV-MCL) is a rare variant and has a more aggressive clinical course. The phenotype of BV-MCL is characterized as CD20+, CD5+, cyclin D1+, CD23-, and CD10-. Interphase fluorescence in situ hybridization shows a characteristic t(11;14) fusion pattern. We report a case of a BV-MCL arising in skin as primary cutaneous MCL with the characteristic immunophenotype and translocation.

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Blastoid and common variants of mantle cell lymphoma exhibit distinct immunophenotypic and interphase FISH features

Abstract: Since distinction between BV and common MCL is of clinical relevance, our data underline the need to add phenotypic and cytogenetic criteria to cytomorphology for a better recognition of BV-MCL.

Cited by 30 publications

References 34 publications

Immunophenotypic profile and clinical characteristics in patients with advanced stage mantle cell lymphoma

Immunophenotypic profile and clinical characteristics in patients with advanced stage mantle cell lymphoma

Point mutations and genomic deletions in CCND1 create stable truncated cyclin D1 mRNAs that are associated with increased proliferation rate and shorter survival

Primary Cutaneous Blastoid Mantle Cell Lymphoma-Case Report

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