Molecular characterization of heavy chain immunoglobulin gene rearrangements in Waldenstrom's macroglobulinemia and IgM monoclonal gammopathy of undetermined significance

Martín-Jiménez, Patricia; García‐Sanz, Ramón; Balanzategui, Ana; Alcoceba, Miguel; Ocio, Enrique M.; Sánchez, María Luz; González, Marcos; Miguel, Jesús F. San

doi:10.3324/haematol.10755

Cited by 51 publications

(39 citation statements)

References 35 publications

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“…When compared to VH distribution of normal B cells, SMZL cases appeared to be characterized by an increased usage of VH1 (45% in our study versus 7.1% in normal B cells, P ¼ 0.01). As previously described in LPL, 3 we found a marked VH3 restriction usage (78.3% of LPL cases in our study versus 33.1% in normal B cells) with a highly significant predominance of VH3-23 subtype (w 2 test, Po10 À6 ).…”

supporting

confidence: 60%

“…2 In contrast, IgVH somatic mutations are frequent with a predominance of VH3 usage in LPL patients. 3 But, it is worthnoting that these results are not fully conclusive because they have been obtained on heterogeneous biological materials and in different separated series.…”

mentioning

confidence: 89%

“…3 In addition, we have reported that pharmacologic inhibition of Src family kinases results in enhancement of ATRA-induced myeloid differentiation. 4 These results indicate that tyrosine kinases in the Src family kinase family act as negative regulators of ATRA-induced differentiation.…”

Section: Letters To the Editormentioning

confidence: 99%

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Splenic marginal zone lymphomas and lymphoplasmacytic lymphomas originate from B-cell compartments with two different antigen-exposure histories

et al. 2008

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supporting

confidence: 60%

mentioning

confidence: 89%

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Splenic marginal zone lymphomas and lymphoplasmacytic lymphomas originate from B-cell compartments with two different antigen-exposure histories

et al. 2008

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“…26 Lymphoplasmacytic lymphoma mostly uses IGHV3 family genes and shows >5% somatic hypermutation, whereas the mutation rate in CAD-associated lymphoproliferative disease is lower. 16,27,28 Importantly, the MYD88 L265P mutation, present in over 90% of cases of lymphoplasmacytic lymphoma, was not found in any of the CAD samples that were tested in our series. 16,17 Furthermore, the bone marrow disease in CAD patients is not typical of that seen in other small cell variants of Bcell non-Hodgkin lymphomas such as follicular lymphoma, chronic lymphocytic leukemia and mantle cell lymphoma because cytological and immunophenotypic characteristics typical of these lymphomas are lacking.…”

mentioning

confidence: 96%

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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“…The CXCL12/CXCR4-axis plays a major role in the homing of WM cells to these protective niches. Furthermore, WM cells express a biased IgHV repertoire, 4 suggesting that (antigen-dependent) BCR signaling plays a role in the pathogenesis of WM.…”

mentioning

confidence: 99%

Ibrutinib and idelalisib target B cell receptor- but not CXCL12/CXCR4-controlled integrin-mediated adhesion in Waldenstrom macroglobulinemia

et al. 2015

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Molecular characterization of heavy chain immunoglobulin gene rearrangements in Waldenstrom's macroglobulinemia and IgM monoclonal gammopathy of undetermined significance

Cited by 51 publications

References 35 publications

Splenic marginal zone lymphomas and lymphoplasmacytic lymphomas originate from B-cell compartments with two different antigen-exposure histories

Splenic marginal zone lymphomas and lymphoplasmacytic lymphomas originate from B-cell compartments with two different antigen-exposure histories

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

Ibrutinib and idelalisib target B cell receptor- but not CXCL12/CXCR4-controlled integrin-mediated adhesion in Waldenstrom macroglobulinemia

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