Analysis of BCL-6, CD95, PIM1, RHO/TTF and PAX5 mutations in splenic and nodal marginal zone B-cell lymphomas suggests a particular B-cell origin

Traverse-Gléhen, Alexandra; Verney, Aurélie; Baseggio, Lucille; Felman, Pascale; Callet‐Bauchu, Evelyne; Thiéblemont, Catherine; Ffrench, Martine; Jp, Magaud; Berger, Françoise; Salles, Gilles

doi:10.1038/sj.leu.2404706

Cited by 25 publications

(19 citation statements)

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“…The IGHV3-23*01 or *04 gene was involved, as has already been reported for SMZL (Arcaini et al, 2009). This case displayed unmutated BCL6 gene and FAS loci, as expected (Mateo et al, 2001;Traverse-Glehen et al, 2007).…”

Section: Smzl Casesupporting

confidence: 61%

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In non‐follicular lymphoproliferative disorders, IGH/BCL2‐fusion is not restricted to chronic lymphocytic leukaemia

et al. 2012

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SummaryThe translocation t(14;18) and its t(2;18) and t(18,22) variants, which involve the BCL2 genetic hallmark for follicular lymphoma (FL), have been reported in several cases of chronic B‐cell lymphoproliferative disease (CLPD) and frequently in chronic lymphocytic leukaemia (CLL). We describe here the clinical, morphological, immunological, cytogenetic and molecular findings from 37 cases of t(14;18)‐positive CLPD, identified from our series of non‐FL B‐cell neoplasms (n = 993) that were routinely analysed in peripheral blood by conventional cytogenetics analyses. The FL diagnosis was excluded by morphology and immunology (the samples were CD10 negative in all cases). The BCL2 translocations were observed in 22 CLL cases, including 7 monoclonal B‐cell lymphocytosis (MBL) cases re‐classified according to the new International Workshop on CLL criteria, six small lymphocytic lymphoma (SLL) cases, 1 splenic marginal zone lymphoma (SMZL) case and eight cases of unclassifiable CLPD with overlapping CLL/MZL features. In the CLL cases, the IGH/BCL2 fusion was remarkably associated with trisomy 12 (13/22) and mutated IGHV status (20/21) and did not affect the outcome. Moreover, most of these CLLs harboured a low mutation load of BCL6 gene and unmutated FAS (CD95) loci, which points to a post–germinal‐centre cellular origin.

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Section: Smzl Casesupporting

confidence: 61%

“…The BCL6 (region located downstream to the first noncoding BCL6 exon) and FAS (exon 8, exon 9 and 5′UTR) nucleotide sequence analyses were obtained by directly sequencing the amplified PCR fragments in 23 cases, as has been previously described (Traverse-Glehen et al, 2007).…”

Section: Molecular Analysismentioning

confidence: 99%

In non‐follicular lymphoproliferative disorders, IGH/BCL2‐fusion is not restricted to chronic lymphocytic leukaemia

et al. 2012

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“…36 The absence of mutations in BCL6, a gene highly expressed in germinal center B cells and hence also affected by somatic hypermutation in those cells, is an argument in favor of the origin of the clonal B cells in CAD being B cells that have acquired somatic hypermutation without passing through the germinal center. 37 Of interest, normal IGHV4-34-expressing B cells home with preference to the splenic marginal zone and are not normally recruited to the germinal center, except in auto-immune diseases such as lupus erythematosus.…”

Section: © F E R R a T A S T O R T I F O U N D A T I O Nmentioning

confidence: 99%

Primary cold agglutinin-associated lymphoproliferative disease: a B-cell lymphoma of the bone marrow distinct from lymphoplasmacytic lymphoma

et al. 2013

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© F e r r a t a S t o r t i F o u n d a t i o nCAD diagnosed in the time period between 1995 and 2012 were studied. There were 36 women and 18 men with an age range of 40-92 (median 73) years. All patients had a clinical history of CAD with a variable degree of anemia, a positive C3d-specific direct antiglobulin test and a cold agglutinin titer in excess of 64. Monoclonal IgM had been detected in the serum of all patients by agarose electrophoresis and immunofixation. None of the patients had lymphadenopathy or splenomegaly. Clinical follow-up ranged from 3 to 152 months, with a median follow-up of 72 months. The study was approved by the institutional and regional ethical committees. Biopsy materialArchival hematoxylin and eosin-stained sections of bone marrow trephine biopsies from the 54 patients, obtained at diagnosis, were reviewed. Fourteen biopsies were fixed in 4% formaldehyde, 18 in Bplus fixative and 22 in B5 fixative. In addition, part of the diagnostic trephine biopsy of eight patients had been snap-frozen in liquid nitrogen. Two of the patients had undergone splenectomy in an attempt to reduce hemolysis. Hematoxylin and eosin-stained archival sections of formalin-fixed splenic tissue of these patients were reviewed. ImmunohistochemistryImmunohistochemical analysis was extended or repeated whenever archival sections were not available or of bad quality. The primary antibodies and the method used for immunohistochemical analysis of the bone marrow trephine biopsies are described in the Online Supplementary Methods. Flow cytometryFlow cytometry was performed on samples from 25 patients and included a total of 46 bone marrow and 10 paired peripheral blood samples, anticoagulated with heparin and EDTA, respectively. On samples analyzed before 2011, a four-color analysis 18 and from 2011 onwards, an eight-color analysis 19 was performed with antibody combinations as described in the Online Supplementary Methods.Immunoglobulin heavy chain gene sequencing, and BCL6 and MYD88 mutation analyses DNA was extracted from frozen bone marrow trephine samples, obtained from eight patients, using the EZ1 tissue kit (Qiagen, Hilden, Germany) and from formaldehyde-fixed paraffin embedded-tissue sections from another nine patients using the QIAamp DNA FFPE tissue kit (Qiagen). Immunoglobulin heavy chain gene analysis and BCL6 intron 1 mutation analysis was only performed on DNA from frozen tissue samples whereas MYD88 mutation analysis, requiring less intact DNA, was performed on frozen and formaldehyde-fixed tissue samples.BCL6 intron 1 was amplified using three sets of overlapping polymerase chain reaction (PCR) primers covering nucleotides 24 to 790 in GenBank sequence AF191831. The primer pairs and PCR conditions are described in the Online Supplementary Methods. PCR products were sequenced and analyzed using the BLAST database.The MYD88 L265P mutation (NM_002468) was analyzed using PCR and a SNaPshot multiplex kit (Applied Biosystems). PCR primers and conditions are described in the Online Supplementary Me...

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“…In particular, the expression of Pim1 has been correlated with measures of clinical outcome (8). Moreover, pim1 was recently identified as a target of aberrant somatic hypermutation in non-Hodgkin's lymphoma and B-cell lymphoma (9)(10)(11), and some of the mutations significantly increase Pim1 enzymatic activity (12). Thus, it is suggested that Pim kinase overexpression and activation induce tumorigenesis.…”

Section: Introductionmentioning

confidence: 99%

Pim Kinases Promote Cell Cycle Progression by Phosphorylating and Down-regulating p27Kip1 at the Transcriptional and Posttranscriptional Levels

et al. 2008

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Analysis of BCL-6, CD95, PIM1, RHO/TTF and PAX5 mutations in splenic and nodal marginal zone B-cell lymphomas suggests a particular B-cell origin

Cited by 25 publications

References 10 publications

In non‐follicular lymphoproliferative disorders, IGH/BCL2‐fusion is not restricted to chronic lymphocytic leukaemia

In non‐follicular lymphoproliferative disorders, IGH/BCL2‐fusion is not restricted to chronic lymphocytic leukaemia

Primary cold agglutinin-associated lymphoproliferative disease: a B-cell lymphoma of the bone marrow distinct from lymphoplasmacytic lymphoma

Pim Kinases Promote Cell Cycle Progression by Phosphorylating and Down-regulating p27Kip1 at the Transcriptional and Posttranscriptional Levels

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