The Experts below are selected from a list of 10242 Experts worldwide ranked by ideXlab platform
Lucile Baseggio - One of the best experts on this subject based on the ideXlab platform.
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Toll-like receptor expression and function differ between splenic marginal zone B cell lymphoma and splenic diffuse Red Pulp B cell lymphoma
Oncotarget, 2018Co-Authors: Aurelie Verney, Jean-pierre Magaud, Alexandra Traverse-glehen, Evelyne Callet-bauchu, Gilles Salles, Laurent Jallades, Laurent Genestier, Lucile BaseggioAbstract:In splenic marginal zone lymphoma (SMZL), specific and functional Toll-like Receptor (TLR) patterns have been recently described, suggesting their involvement in tumoral proliferation. Splenic diffuse Red Pulp lymphoma with villous lymphocytes (SDRPL) is close to but distinct from SMZL, justifying here the comparison of TLR patterns and functionality in both entities. Distinct TLR profiles were observed in both lymphoma subtypes. SDRPL B cells showed higher expression of TLR7 and to a lesser degree TLR9, in comparison to SMZL B cells. In both entities, TLR7 and TLR9 pathways appeaRed functional, as shown by IL-6 production upon TLR7 and TLR9 agonists stimulations. Interestingly, circulating SDRPL, but not SMZL B cells, constitutively expressed CD86. In addition, stimulation with both TLR7 and TLR9 agonists significantly increased CD80 expression in circulating SDRPL but not SMZL B cells. Finally, TLR7 and TLR9 stimulations had no impact on proliferation and apoptosis of SMZL or SDRPL B cells. In conclusion, SMZL and SDRPL may derive from different splenic memory B cells with specific immunological features that can be used as diagnosis markers in the peripheral blood.
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Exome sequencing identifies recurrent BCOR alterations and the absence of KLF2, TNFAIP3 and MYD88 mutations in splenic diffuse Red Pulp small B-cell lymphoma.
Haematologica, 2017Co-Authors: Laurent Jallades, Lucile Baseggio, Aurelie Verney, Evelyne Callet-bauchu, Pierre Sujobert, Sarah Huet, Kaddour Chabane, Sandrine Hayette, Jean-pierre Desvignes, David SalgadoAbstract:Splenic diffuse Red Pulp lymphoma is an indolent small B-cell lymphoma recognised as a provisional entity in the WHO 2008 classification. Its precise relationship with other related splenic B-cell lymphomas with frequent leukaemic involvement or other lymphoproliferative disorders remains undetermined. We performed whole-exome sequencing to explore the genetic landscape of 10 splenic diffuse Red Pulp lymphoma cases from paiRed tumour and normal samples. A selection of 109 somatic mutations was then evaluated in a cohort including 42 splenic diffuse Red Pulp lymphoma samples and compaRed to those identified in 46 splenic marginal zone lymphoma and 8 hairy-cell leukaemia samples. Recurrent mutations or losses in BCOR (gene encoding the BCL6 corepressor)-frameshift (n=3), nonsense (n=2), splicing site (n=1), and copy number loss (n=4)- were identified in 10/42 splenic diffuse Red Pulp lymphoma (24%), whereas only one frameshift mutation was identified in 46 splenic marginal zone lymphoma cases (2%). Inversely, KLF2, TNFAIP3 and MYD88 mutations were rare (one KLF2 mutant out of 42 samples; 2%) or absent (TNFAIP3 and MYD88) in splenic diffuse Red Pulp lymphoma compaRed to splenic marginal zone lymphoma. These findings define an original genetic profile of splenic diffuse Red Pulp lymphoma, suggesting distinct mechanisms of pathogenesis from splenic marginal zone lymphoma and hairy-cell leukaemia.
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exome sequencing identifies recurrent bcor alterations and the absence of klf2 tnfaip3 and myd88 mutations in splenic diffuse Red Pulp small b cell lymphoma
Haematologica, 2017Co-Authors: Laurent Jallades, Lucile Baseggio, Pierre Sujobert, Sarah Huet, Kaddour Chabane, Evelyne Calletbauchu, Aurelie VerneyAbstract:Splenic diffuse Red Pulp lymphoma is an indolent small B-cell lymphoma recognized as a provisional entity in the World Health Organization 2008 classification. Its precise relationship to other related splenic B-cell lymphomas with frequent leukemic involvement or other lymphoproliferative disorders remains undetermined. We performed whole-exome sequencing to explore the genetic landscape of ten cases of splenic diffuse Red Pulp lymphoma using paiRed tumor and normal samples. A selection of 109 somatic mutations was then evaluated in a cohort including 42 samples of splenic diffuse Red Pulp lymphoma and compaRed to those identified in 46 samples of splenic marginal zone lymphoma and eight samples of hairy-cell leukemia. Recurrent mutations or losses in BCOR (the gene encoding the BCL6 corepressor) – frameshift (n=3), nonsense (n=2), splicing site (n=1), and copy number loss (n=4) – were identified in 10/42 samples of splenic diffuse Red Pulp lymphoma (24%), whereas only one frameshift mutation was identified in 46 cases of splenic marginal zone lymphoma (2%). Inversely, KLF2, TNFAIP3 and MYD88, common mutations in splenic marginal zone lymphoma, were rare (one KLF2 mutant in 42 samples; 2%) or absent (TNFAIP3 and MYD88) in splenic diffuse Red Pulp lymphoma. These findings define an original genetic profile of splenic diffuse Red Pulp lymphoma and suggest that the mechanisms of pathogenesis of this lymphoma are distinct from those of splenic marginal zone lymphoma and hairy-cell leukemia.
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Mutational Status of Splenic Diffuse Red Pulp Small B-Cell Lymphoma Revealed By Whole Exome Sequencing
Blood, 2015Co-Authors: Nerea Martinez, Lucile Baseggio, Aurelie Verney, Alexandra Traverse-glehen, Carmen Almaraz, Manuela Mollejo, Laura Cereceda, Sophia Derdak, Yolanda Campos-martín, Fanny CamachoAbstract:Background : Splenic diffuse Red Pulp lymphoma (SDRPL) is a rare small B cell neoplasm provisionally included in a category of unclassifiable splenic B-cell lymphoma/leukemias in the 2008 WHO classification. SDRPL is characterized by a diffuse pattern of involvement of the splenic Red Pulp by small monomorphous B lymphocytes. Patients are normally diagnosed at stage IV when spleen, bone marrow and peripheral blood are involved. This indolent but incurable disease is more common in aged males and it shows with splenomegaly and moderate lymphocytosis. The differential diagnosis with other splenic lymphomas such as marginal zone lymphoma, hairy cell lymphoma and its variant is not always easy, due to the similar clinical presentation and the absence of specific molecular markers. Here we studied the mutational status of 15 SDRPL patients using Whole Exome Next Generation Sequencing. Methods : Genomic DNA was extracted from FFPE/FF splenic tumor or bone marrow samples. When available, DNA from oral mucosa was obtained as the corresponding non-tumor control. Whole exome sequencing was performed at CNAG (Barcelona, Spain) following standard protocols for high-throughput paiRed-end sequencing on the Illumina HiSeq2000 instruments (Illumina Inc., San Diego, CA). Validation of variants was performed by PCR based targeted resequencing using a MiSeq instrument (Illumina Inc., San Diego, CA). We performed paiRed-end-76pb whole exome sequencing on DNA from 15 SDRPL patients. The corresponding normal counterpart from 3 of the patients was sequenced. From one patient FFPE and bone marrow DNA was available for comparison. In total 9 FFPE tissue samples, 3 FF tissue samples, and 4 bone marrow samples were sequenced. Almost 95% of the selected variants were validated by PCR based resequencing in 9 of the patients, while from 6 of the patients no tissue was available for validation. Results : 290 substitutions and 26 indels were obtained after filtering. Whole exome sequencing permitted us to identify variations in several genes of relevant pathways in lymphomas, such as NFkB pathway (IkBKB, TRAF, TANK, SYK), Apoptosis (BAD, DCPS, BCLAF1), MAPK (CXCR4, TCF3, NF1, MAP3K5), Cell cycle (CCND3, POLD3, BUB1), Chromatin (CREBBP, ARID1A, ARID1B, ARID3A, MLL3), MYC regulators (AKAP10, CTCF, EP400) or WNT signaling (SALL1, WNT5B, GPC6). Moreover, CCND3 and MLL3 were recurrently mutated in 2 different patients. Genes specifically found mutated in other splenic malignancies, such as NOTCH2, BRAF, MAP2K1, and KLF2 were not found mutated in this series of SDRPL patients. Conclusions: SDRPL samples contain somatic mutations involving genes regulating relevant pathways for cell survival, such as NFkB, apoptosis, cell cycle, chromatin, or WNT. The mutational signature of the series studied here may indicate that SDRPL is a distinct entity with specific molecular features different to other lymphoid splenic malignancies. Disclosures No relevant conflicts of interest to declare.
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Splenic diffuse Red Pulp small-B cell lymphoma: toward the emergence of a new lymphoma entity.
Discovery medicine, 2012Co-Authors: Alexandra Traverse-glehen, Lucile Baseggio, Gilles Salles, Pascale Felman, Bertrand Coiffier, Françoise BergerAbstract:Among splenic lymphomas with circulating cells presenting cytoplasmic projections, a homogeneous clinico-pathological entity has been recently individualized as Splenic Diffuse Red Pulp Lymphomas (SDRPL) and introduced in the provisional "unclassifiable splenic lymphoma" category of the current updated WHO classification until more is known. SDRPL presents characteristic circulating basophilic villous lymphocytes and diffuse infiltration of the splenic Red Pulp, distinct from Splenic Marginal Zone Lymphoma (SMZL) and Hairy Cell Leukemia (HCL), but reminiscent of HCL-Variant (HCL-V). Series of SDRPL remain sparse in the literature and controversies exist about the relationship with other splenic lymphomas. Distinction of these disorders at diagnosis can be difficult, but an adequate diagnosis is important due to differences in patient management and clinical outcome. Especially, BRAF mutations have been detected in almost all patients with HCL that may have implications for pathogenesis, diagnosis, and targeted therapy. This review will report literature data and discuss the differential diagnosis, particularly with HCL-V.
Aurelie Verney - One of the best experts on this subject based on the ideXlab platform.
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Toll-like receptor expression and function differ between splenic marginal zone B cell lymphoma and splenic diffuse Red Pulp B cell lymphoma
Oncotarget, 2018Co-Authors: Aurelie Verney, Jean-pierre Magaud, Alexandra Traverse-glehen, Evelyne Callet-bauchu, Gilles Salles, Laurent Jallades, Laurent Genestier, Lucile BaseggioAbstract:In splenic marginal zone lymphoma (SMZL), specific and functional Toll-like Receptor (TLR) patterns have been recently described, suggesting their involvement in tumoral proliferation. Splenic diffuse Red Pulp lymphoma with villous lymphocytes (SDRPL) is close to but distinct from SMZL, justifying here the comparison of TLR patterns and functionality in both entities. Distinct TLR profiles were observed in both lymphoma subtypes. SDRPL B cells showed higher expression of TLR7 and to a lesser degree TLR9, in comparison to SMZL B cells. In both entities, TLR7 and TLR9 pathways appeaRed functional, as shown by IL-6 production upon TLR7 and TLR9 agonists stimulations. Interestingly, circulating SDRPL, but not SMZL B cells, constitutively expressed CD86. In addition, stimulation with both TLR7 and TLR9 agonists significantly increased CD80 expression in circulating SDRPL but not SMZL B cells. Finally, TLR7 and TLR9 stimulations had no impact on proliferation and apoptosis of SMZL or SDRPL B cells. In conclusion, SMZL and SDRPL may derive from different splenic memory B cells with specific immunological features that can be used as diagnosis markers in the peripheral blood.
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Exome sequencing identifies recurrent BCOR alterations and the absence of KLF2, TNFAIP3 and MYD88 mutations in splenic diffuse Red Pulp small B-cell lymphoma.
Haematologica, 2017Co-Authors: Laurent Jallades, Lucile Baseggio, Aurelie Verney, Evelyne Callet-bauchu, Pierre Sujobert, Sarah Huet, Kaddour Chabane, Sandrine Hayette, Jean-pierre Desvignes, David SalgadoAbstract:Splenic diffuse Red Pulp lymphoma is an indolent small B-cell lymphoma recognised as a provisional entity in the WHO 2008 classification. Its precise relationship with other related splenic B-cell lymphomas with frequent leukaemic involvement or other lymphoproliferative disorders remains undetermined. We performed whole-exome sequencing to explore the genetic landscape of 10 splenic diffuse Red Pulp lymphoma cases from paiRed tumour and normal samples. A selection of 109 somatic mutations was then evaluated in a cohort including 42 splenic diffuse Red Pulp lymphoma samples and compaRed to those identified in 46 splenic marginal zone lymphoma and 8 hairy-cell leukaemia samples. Recurrent mutations or losses in BCOR (gene encoding the BCL6 corepressor)-frameshift (n=3), nonsense (n=2), splicing site (n=1), and copy number loss (n=4)- were identified in 10/42 splenic diffuse Red Pulp lymphoma (24%), whereas only one frameshift mutation was identified in 46 splenic marginal zone lymphoma cases (2%). Inversely, KLF2, TNFAIP3 and MYD88 mutations were rare (one KLF2 mutant out of 42 samples; 2%) or absent (TNFAIP3 and MYD88) in splenic diffuse Red Pulp lymphoma compaRed to splenic marginal zone lymphoma. These findings define an original genetic profile of splenic diffuse Red Pulp lymphoma, suggesting distinct mechanisms of pathogenesis from splenic marginal zone lymphoma and hairy-cell leukaemia.
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exome sequencing identifies recurrent bcor alterations and the absence of klf2 tnfaip3 and myd88 mutations in splenic diffuse Red Pulp small b cell lymphoma
Haematologica, 2017Co-Authors: Laurent Jallades, Lucile Baseggio, Pierre Sujobert, Sarah Huet, Kaddour Chabane, Evelyne Calletbauchu, Aurelie VerneyAbstract:Splenic diffuse Red Pulp lymphoma is an indolent small B-cell lymphoma recognized as a provisional entity in the World Health Organization 2008 classification. Its precise relationship to other related splenic B-cell lymphomas with frequent leukemic involvement or other lymphoproliferative disorders remains undetermined. We performed whole-exome sequencing to explore the genetic landscape of ten cases of splenic diffuse Red Pulp lymphoma using paiRed tumor and normal samples. A selection of 109 somatic mutations was then evaluated in a cohort including 42 samples of splenic diffuse Red Pulp lymphoma and compaRed to those identified in 46 samples of splenic marginal zone lymphoma and eight samples of hairy-cell leukemia. Recurrent mutations or losses in BCOR (the gene encoding the BCL6 corepressor) – frameshift (n=3), nonsense (n=2), splicing site (n=1), and copy number loss (n=4) – were identified in 10/42 samples of splenic diffuse Red Pulp lymphoma (24%), whereas only one frameshift mutation was identified in 46 cases of splenic marginal zone lymphoma (2%). Inversely, KLF2, TNFAIP3 and MYD88, common mutations in splenic marginal zone lymphoma, were rare (one KLF2 mutant in 42 samples; 2%) or absent (TNFAIP3 and MYD88) in splenic diffuse Red Pulp lymphoma. These findings define an original genetic profile of splenic diffuse Red Pulp lymphoma and suggest that the mechanisms of pathogenesis of this lymphoma are distinct from those of splenic marginal zone lymphoma and hairy-cell leukemia.
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Splenic diffuse Red Pulp lymphoma has a distinct pattern of somatic mutations amongst B-cell malignancies.
Leukemia & lymphoma, 2016Co-Authors: Alexandra Traverse-glehen, Sophie Gazzo, Aurelie Verney, Martine Ffrench, Evelyne Callet-bauchu, Laurent Jallades, Kaddour Chabane, Sandrine Hayette, Bertrand Coiffier, Pascale FelmanAbstract:Splenic Diffuse Red Pulp Lymphoma (SDRPL) has been recently introduced as a provisional entity but differential diagnosis with other splenic lymphomas is needed to be clarified since the therapeutic approaches are distinct. Recently described recurrent mutations or CD180 expression appear useful for differential diagnosis. We completed our previous description in a larger cohort including 53 patients selected on the presence of characteristic villous cells in peripheral blood (PB) and a specific immunophenotype. Immunoglobulin heavy variable (IGHV), BRAF, MYD88, and NOTCH2 mutations were determined and CD180 and BRAF expressions were assessed. Most cases (79%) were IGHV mutated with an overrepresentation of IGHV3-23 (19%) and IGHV4-34 (21%). MYD88 L265P and NOTCH2 mutations were observed in one case each, whereas no BRAF V600E mutation or expression was found. All cases demonstrated a high CD180 expression. Those results strengthen the concept that SDRPL does emerge as a new lymphoma entity distinct from the other splenic lymphomas with circulating lymphocytes.
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Mutational Status of Splenic Diffuse Red Pulp Small B-Cell Lymphoma Revealed By Whole Exome Sequencing
Blood, 2015Co-Authors: Nerea Martinez, Lucile Baseggio, Aurelie Verney, Alexandra Traverse-glehen, Carmen Almaraz, Manuela Mollejo, Laura Cereceda, Sophia Derdak, Yolanda Campos-martín, Fanny CamachoAbstract:Background : Splenic diffuse Red Pulp lymphoma (SDRPL) is a rare small B cell neoplasm provisionally included in a category of unclassifiable splenic B-cell lymphoma/leukemias in the 2008 WHO classification. SDRPL is characterized by a diffuse pattern of involvement of the splenic Red Pulp by small monomorphous B lymphocytes. Patients are normally diagnosed at stage IV when spleen, bone marrow and peripheral blood are involved. This indolent but incurable disease is more common in aged males and it shows with splenomegaly and moderate lymphocytosis. The differential diagnosis with other splenic lymphomas such as marginal zone lymphoma, hairy cell lymphoma and its variant is not always easy, due to the similar clinical presentation and the absence of specific molecular markers. Here we studied the mutational status of 15 SDRPL patients using Whole Exome Next Generation Sequencing. Methods : Genomic DNA was extracted from FFPE/FF splenic tumor or bone marrow samples. When available, DNA from oral mucosa was obtained as the corresponding non-tumor control. Whole exome sequencing was performed at CNAG (Barcelona, Spain) following standard protocols for high-throughput paiRed-end sequencing on the Illumina HiSeq2000 instruments (Illumina Inc., San Diego, CA). Validation of variants was performed by PCR based targeted resequencing using a MiSeq instrument (Illumina Inc., San Diego, CA). We performed paiRed-end-76pb whole exome sequencing on DNA from 15 SDRPL patients. The corresponding normal counterpart from 3 of the patients was sequenced. From one patient FFPE and bone marrow DNA was available for comparison. In total 9 FFPE tissue samples, 3 FF tissue samples, and 4 bone marrow samples were sequenced. Almost 95% of the selected variants were validated by PCR based resequencing in 9 of the patients, while from 6 of the patients no tissue was available for validation. Results : 290 substitutions and 26 indels were obtained after filtering. Whole exome sequencing permitted us to identify variations in several genes of relevant pathways in lymphomas, such as NFkB pathway (IkBKB, TRAF, TANK, SYK), Apoptosis (BAD, DCPS, BCLAF1), MAPK (CXCR4, TCF3, NF1, MAP3K5), Cell cycle (CCND3, POLD3, BUB1), Chromatin (CREBBP, ARID1A, ARID1B, ARID3A, MLL3), MYC regulators (AKAP10, CTCF, EP400) or WNT signaling (SALL1, WNT5B, GPC6). Moreover, CCND3 and MLL3 were recurrently mutated in 2 different patients. Genes specifically found mutated in other splenic malignancies, such as NOTCH2, BRAF, MAP2K1, and KLF2 were not found mutated in this series of SDRPL patients. Conclusions: SDRPL samples contain somatic mutations involving genes regulating relevant pathways for cell survival, such as NFkB, apoptosis, cell cycle, chromatin, or WNT. The mutational signature of the series studied here may indicate that SDRPL is a distinct entity with specific molecular features different to other lymphoid splenic malignancies. Disclosures No relevant conflicts of interest to declare.
Laurent Jallades - One of the best experts on this subject based on the ideXlab platform.
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Toll-like receptor expression and function differ between splenic marginal zone B cell lymphoma and splenic diffuse Red Pulp B cell lymphoma
Oncotarget, 2018Co-Authors: Aurelie Verney, Jean-pierre Magaud, Alexandra Traverse-glehen, Evelyne Callet-bauchu, Gilles Salles, Laurent Jallades, Laurent Genestier, Lucile BaseggioAbstract:In splenic marginal zone lymphoma (SMZL), specific and functional Toll-like Receptor (TLR) patterns have been recently described, suggesting their involvement in tumoral proliferation. Splenic diffuse Red Pulp lymphoma with villous lymphocytes (SDRPL) is close to but distinct from SMZL, justifying here the comparison of TLR patterns and functionality in both entities. Distinct TLR profiles were observed in both lymphoma subtypes. SDRPL B cells showed higher expression of TLR7 and to a lesser degree TLR9, in comparison to SMZL B cells. In both entities, TLR7 and TLR9 pathways appeaRed functional, as shown by IL-6 production upon TLR7 and TLR9 agonists stimulations. Interestingly, circulating SDRPL, but not SMZL B cells, constitutively expressed CD86. In addition, stimulation with both TLR7 and TLR9 agonists significantly increased CD80 expression in circulating SDRPL but not SMZL B cells. Finally, TLR7 and TLR9 stimulations had no impact on proliferation and apoptosis of SMZL or SDRPL B cells. In conclusion, SMZL and SDRPL may derive from different splenic memory B cells with specific immunological features that can be used as diagnosis markers in the peripheral blood.
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Exome sequencing identifies recurrent BCOR alterations and the absence of KLF2, TNFAIP3 and MYD88 mutations in splenic diffuse Red Pulp small B-cell lymphoma.
Haematologica, 2017Co-Authors: Laurent Jallades, Lucile Baseggio, Aurelie Verney, Evelyne Callet-bauchu, Pierre Sujobert, Sarah Huet, Kaddour Chabane, Sandrine Hayette, Jean-pierre Desvignes, David SalgadoAbstract:Splenic diffuse Red Pulp lymphoma is an indolent small B-cell lymphoma recognised as a provisional entity in the WHO 2008 classification. Its precise relationship with other related splenic B-cell lymphomas with frequent leukaemic involvement or other lymphoproliferative disorders remains undetermined. We performed whole-exome sequencing to explore the genetic landscape of 10 splenic diffuse Red Pulp lymphoma cases from paiRed tumour and normal samples. A selection of 109 somatic mutations was then evaluated in a cohort including 42 splenic diffuse Red Pulp lymphoma samples and compaRed to those identified in 46 splenic marginal zone lymphoma and 8 hairy-cell leukaemia samples. Recurrent mutations or losses in BCOR (gene encoding the BCL6 corepressor)-frameshift (n=3), nonsense (n=2), splicing site (n=1), and copy number loss (n=4)- were identified in 10/42 splenic diffuse Red Pulp lymphoma (24%), whereas only one frameshift mutation was identified in 46 splenic marginal zone lymphoma cases (2%). Inversely, KLF2, TNFAIP3 and MYD88 mutations were rare (one KLF2 mutant out of 42 samples; 2%) or absent (TNFAIP3 and MYD88) in splenic diffuse Red Pulp lymphoma compaRed to splenic marginal zone lymphoma. These findings define an original genetic profile of splenic diffuse Red Pulp lymphoma, suggesting distinct mechanisms of pathogenesis from splenic marginal zone lymphoma and hairy-cell leukaemia.
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exome sequencing identifies recurrent bcor alterations and the absence of klf2 tnfaip3 and myd88 mutations in splenic diffuse Red Pulp small b cell lymphoma
Haematologica, 2017Co-Authors: Laurent Jallades, Lucile Baseggio, Pierre Sujobert, Sarah Huet, Kaddour Chabane, Evelyne Calletbauchu, Aurelie VerneyAbstract:Splenic diffuse Red Pulp lymphoma is an indolent small B-cell lymphoma recognized as a provisional entity in the World Health Organization 2008 classification. Its precise relationship to other related splenic B-cell lymphomas with frequent leukemic involvement or other lymphoproliferative disorders remains undetermined. We performed whole-exome sequencing to explore the genetic landscape of ten cases of splenic diffuse Red Pulp lymphoma using paiRed tumor and normal samples. A selection of 109 somatic mutations was then evaluated in a cohort including 42 samples of splenic diffuse Red Pulp lymphoma and compaRed to those identified in 46 samples of splenic marginal zone lymphoma and eight samples of hairy-cell leukemia. Recurrent mutations or losses in BCOR (the gene encoding the BCL6 corepressor) – frameshift (n=3), nonsense (n=2), splicing site (n=1), and copy number loss (n=4) – were identified in 10/42 samples of splenic diffuse Red Pulp lymphoma (24%), whereas only one frameshift mutation was identified in 46 cases of splenic marginal zone lymphoma (2%). Inversely, KLF2, TNFAIP3 and MYD88, common mutations in splenic marginal zone lymphoma, were rare (one KLF2 mutant in 42 samples; 2%) or absent (TNFAIP3 and MYD88) in splenic diffuse Red Pulp lymphoma. These findings define an original genetic profile of splenic diffuse Red Pulp lymphoma and suggest that the mechanisms of pathogenesis of this lymphoma are distinct from those of splenic marginal zone lymphoma and hairy-cell leukemia.
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Splenic diffuse Red Pulp lymphoma has a distinct pattern of somatic mutations amongst B-cell malignancies.
Leukemia & lymphoma, 2016Co-Authors: Alexandra Traverse-glehen, Sophie Gazzo, Aurelie Verney, Martine Ffrench, Evelyne Callet-bauchu, Laurent Jallades, Kaddour Chabane, Sandrine Hayette, Bertrand Coiffier, Pascale FelmanAbstract:Splenic Diffuse Red Pulp Lymphoma (SDRPL) has been recently introduced as a provisional entity but differential diagnosis with other splenic lymphomas is needed to be clarified since the therapeutic approaches are distinct. Recently described recurrent mutations or CD180 expression appear useful for differential diagnosis. We completed our previous description in a larger cohort including 53 patients selected on the presence of characteristic villous cells in peripheral blood (PB) and a specific immunophenotype. Immunoglobulin heavy variable (IGHV), BRAF, MYD88, and NOTCH2 mutations were determined and CD180 and BRAF expressions were assessed. Most cases (79%) were IGHV mutated with an overrepresentation of IGHV3-23 (19%) and IGHV4-34 (21%). MYD88 L265P and NOTCH2 mutations were observed in one case each, whereas no BRAF V600E mutation or expression was found. All cases demonstrated a high CD180 expression. Those results strengthen the concept that SDRPL does emerge as a new lymphoma entity distinct from the other splenic lymphomas with circulating lymphocytes.
Alexandra Traverse-glehen - One of the best experts on this subject based on the ideXlab platform.
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Toll-like receptor expression and function differ between splenic marginal zone B cell lymphoma and splenic diffuse Red Pulp B cell lymphoma
Oncotarget, 2018Co-Authors: Aurelie Verney, Jean-pierre Magaud, Alexandra Traverse-glehen, Evelyne Callet-bauchu, Gilles Salles, Laurent Jallades, Laurent Genestier, Lucile BaseggioAbstract:In splenic marginal zone lymphoma (SMZL), specific and functional Toll-like Receptor (TLR) patterns have been recently described, suggesting their involvement in tumoral proliferation. Splenic diffuse Red Pulp lymphoma with villous lymphocytes (SDRPL) is close to but distinct from SMZL, justifying here the comparison of TLR patterns and functionality in both entities. Distinct TLR profiles were observed in both lymphoma subtypes. SDRPL B cells showed higher expression of TLR7 and to a lesser degree TLR9, in comparison to SMZL B cells. In both entities, TLR7 and TLR9 pathways appeaRed functional, as shown by IL-6 production upon TLR7 and TLR9 agonists stimulations. Interestingly, circulating SDRPL, but not SMZL B cells, constitutively expressed CD86. In addition, stimulation with both TLR7 and TLR9 agonists significantly increased CD80 expression in circulating SDRPL but not SMZL B cells. Finally, TLR7 and TLR9 stimulations had no impact on proliferation and apoptosis of SMZL or SDRPL B cells. In conclusion, SMZL and SDRPL may derive from different splenic memory B cells with specific immunological features that can be used as diagnosis markers in the peripheral blood.
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Splenic diffuse Red Pulp lymphoma has a distinct pattern of somatic mutations amongst B-cell malignancies.
Leukemia & lymphoma, 2016Co-Authors: Alexandra Traverse-glehen, Sophie Gazzo, Aurelie Verney, Martine Ffrench, Evelyne Callet-bauchu, Laurent Jallades, Kaddour Chabane, Sandrine Hayette, Bertrand Coiffier, Pascale FelmanAbstract:Splenic Diffuse Red Pulp Lymphoma (SDRPL) has been recently introduced as a provisional entity but differential diagnosis with other splenic lymphomas is needed to be clarified since the therapeutic approaches are distinct. Recently described recurrent mutations or CD180 expression appear useful for differential diagnosis. We completed our previous description in a larger cohort including 53 patients selected on the presence of characteristic villous cells in peripheral blood (PB) and a specific immunophenotype. Immunoglobulin heavy variable (IGHV), BRAF, MYD88, and NOTCH2 mutations were determined and CD180 and BRAF expressions were assessed. Most cases (79%) were IGHV mutated with an overrepresentation of IGHV3-23 (19%) and IGHV4-34 (21%). MYD88 L265P and NOTCH2 mutations were observed in one case each, whereas no BRAF V600E mutation or expression was found. All cases demonstrated a high CD180 expression. Those results strengthen the concept that SDRPL does emerge as a new lymphoma entity distinct from the other splenic lymphomas with circulating lymphocytes.
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Mutational Status of Splenic Diffuse Red Pulp Small B-Cell Lymphoma Revealed By Whole Exome Sequencing
Blood, 2015Co-Authors: Nerea Martinez, Lucile Baseggio, Aurelie Verney, Alexandra Traverse-glehen, Carmen Almaraz, Manuela Mollejo, Laura Cereceda, Sophia Derdak, Yolanda Campos-martín, Fanny CamachoAbstract:Background : Splenic diffuse Red Pulp lymphoma (SDRPL) is a rare small B cell neoplasm provisionally included in a category of unclassifiable splenic B-cell lymphoma/leukemias in the 2008 WHO classification. SDRPL is characterized by a diffuse pattern of involvement of the splenic Red Pulp by small monomorphous B lymphocytes. Patients are normally diagnosed at stage IV when spleen, bone marrow and peripheral blood are involved. This indolent but incurable disease is more common in aged males and it shows with splenomegaly and moderate lymphocytosis. The differential diagnosis with other splenic lymphomas such as marginal zone lymphoma, hairy cell lymphoma and its variant is not always easy, due to the similar clinical presentation and the absence of specific molecular markers. Here we studied the mutational status of 15 SDRPL patients using Whole Exome Next Generation Sequencing. Methods : Genomic DNA was extracted from FFPE/FF splenic tumor or bone marrow samples. When available, DNA from oral mucosa was obtained as the corresponding non-tumor control. Whole exome sequencing was performed at CNAG (Barcelona, Spain) following standard protocols for high-throughput paiRed-end sequencing on the Illumina HiSeq2000 instruments (Illumina Inc., San Diego, CA). Validation of variants was performed by PCR based targeted resequencing using a MiSeq instrument (Illumina Inc., San Diego, CA). We performed paiRed-end-76pb whole exome sequencing on DNA from 15 SDRPL patients. The corresponding normal counterpart from 3 of the patients was sequenced. From one patient FFPE and bone marrow DNA was available for comparison. In total 9 FFPE tissue samples, 3 FF tissue samples, and 4 bone marrow samples were sequenced. Almost 95% of the selected variants were validated by PCR based resequencing in 9 of the patients, while from 6 of the patients no tissue was available for validation. Results : 290 substitutions and 26 indels were obtained after filtering. Whole exome sequencing permitted us to identify variations in several genes of relevant pathways in lymphomas, such as NFkB pathway (IkBKB, TRAF, TANK, SYK), Apoptosis (BAD, DCPS, BCLAF1), MAPK (CXCR4, TCF3, NF1, MAP3K5), Cell cycle (CCND3, POLD3, BUB1), Chromatin (CREBBP, ARID1A, ARID1B, ARID3A, MLL3), MYC regulators (AKAP10, CTCF, EP400) or WNT signaling (SALL1, WNT5B, GPC6). Moreover, CCND3 and MLL3 were recurrently mutated in 2 different patients. Genes specifically found mutated in other splenic malignancies, such as NOTCH2, BRAF, MAP2K1, and KLF2 were not found mutated in this series of SDRPL patients. Conclusions: SDRPL samples contain somatic mutations involving genes regulating relevant pathways for cell survival, such as NFkB, apoptosis, cell cycle, chromatin, or WNT. The mutational signature of the series studied here may indicate that SDRPL is a distinct entity with specific molecular features different to other lymphoid splenic malignancies. Disclosures No relevant conflicts of interest to declare.
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Splenic diffuse Red Pulp small-B cell lymphoma: toward the emergence of a new lymphoma entity.
Discovery medicine, 2012Co-Authors: Alexandra Traverse-glehen, Lucile Baseggio, Gilles Salles, Pascale Felman, Bertrand Coiffier, Françoise BergerAbstract:Among splenic lymphomas with circulating cells presenting cytoplasmic projections, a homogeneous clinico-pathological entity has been recently individualized as Splenic Diffuse Red Pulp Lymphomas (SDRPL) and introduced in the provisional "unclassifiable splenic lymphoma" category of the current updated WHO classification until more is known. SDRPL presents characteristic circulating basophilic villous lymphocytes and diffuse infiltration of the splenic Red Pulp, distinct from Splenic Marginal Zone Lymphoma (SMZL) and Hairy Cell Leukemia (HCL), but reminiscent of HCL-Variant (HCL-V). Series of SDRPL remain sparse in the literature and controversies exist about the relationship with other splenic lymphomas. Distinction of these disorders at diagnosis can be difficult, but an adequate diagnosis is important due to differences in patient management and clinical outcome. Especially, BRAF mutations have been detected in almost all patients with HCL that may have implications for pathogenesis, diagnosis, and targeted therapy. This review will report literature data and discuss the differential diagnosis, particularly with HCL-V.
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Relevance of a scoring system including CD11c expression in the identification of splenic diffuse Red Pulp small B-cell lymphoma (SRPL)
Hematological Oncology, 2011Co-Authors: Lucile Baseggio, Dominique Morel, Jean-pierre Magaud, Alexandra Traverse-glehen, Evelyne Callet-bauchu, Françoise Berger, Gilles Salles, Pascale FelmanAbstract:Splenic Red Pulp lymphoma with numerous basophilic villous lymphocytes' (SRPL), recently described, is characterized by clinical, morphologic, immunologic, cytogenetic and molecular features distinct from SMZL/SLVL and HCL. In particular, the intensity of CD11c staining (expressed as fluorescence intensity -RFI-) in SRPL is significantly different from the RFI in SMZL/SLVL and HCL. Moreover the use of a scoring system based on the expression of CD11c, CD22, CD76, CD38 and CD27 appears to improve the differential diagnosis between SRPL and SMZL/SLVL and emphasizes that SRPL is an entity closed to but distinct from SMZL/SLVL. Copyright © 2010 John Wiley & Sons, Ltd.
Evelyne Callet-bauchu - One of the best experts on this subject based on the ideXlab platform.
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Toll-like receptor expression and function differ between splenic marginal zone B cell lymphoma and splenic diffuse Red Pulp B cell lymphoma
Oncotarget, 2018Co-Authors: Aurelie Verney, Jean-pierre Magaud, Alexandra Traverse-glehen, Evelyne Callet-bauchu, Gilles Salles, Laurent Jallades, Laurent Genestier, Lucile BaseggioAbstract:In splenic marginal zone lymphoma (SMZL), specific and functional Toll-like Receptor (TLR) patterns have been recently described, suggesting their involvement in tumoral proliferation. Splenic diffuse Red Pulp lymphoma with villous lymphocytes (SDRPL) is close to but distinct from SMZL, justifying here the comparison of TLR patterns and functionality in both entities. Distinct TLR profiles were observed in both lymphoma subtypes. SDRPL B cells showed higher expression of TLR7 and to a lesser degree TLR9, in comparison to SMZL B cells. In both entities, TLR7 and TLR9 pathways appeaRed functional, as shown by IL-6 production upon TLR7 and TLR9 agonists stimulations. Interestingly, circulating SDRPL, but not SMZL B cells, constitutively expressed CD86. In addition, stimulation with both TLR7 and TLR9 agonists significantly increased CD80 expression in circulating SDRPL but not SMZL B cells. Finally, TLR7 and TLR9 stimulations had no impact on proliferation and apoptosis of SMZL or SDRPL B cells. In conclusion, SMZL and SDRPL may derive from different splenic memory B cells with specific immunological features that can be used as diagnosis markers in the peripheral blood.
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Exome sequencing identifies recurrent BCOR alterations and the absence of KLF2, TNFAIP3 and MYD88 mutations in splenic diffuse Red Pulp small B-cell lymphoma.
Haematologica, 2017Co-Authors: Laurent Jallades, Lucile Baseggio, Aurelie Verney, Evelyne Callet-bauchu, Pierre Sujobert, Sarah Huet, Kaddour Chabane, Sandrine Hayette, Jean-pierre Desvignes, David SalgadoAbstract:Splenic diffuse Red Pulp lymphoma is an indolent small B-cell lymphoma recognised as a provisional entity in the WHO 2008 classification. Its precise relationship with other related splenic B-cell lymphomas with frequent leukaemic involvement or other lymphoproliferative disorders remains undetermined. We performed whole-exome sequencing to explore the genetic landscape of 10 splenic diffuse Red Pulp lymphoma cases from paiRed tumour and normal samples. A selection of 109 somatic mutations was then evaluated in a cohort including 42 splenic diffuse Red Pulp lymphoma samples and compaRed to those identified in 46 splenic marginal zone lymphoma and 8 hairy-cell leukaemia samples. Recurrent mutations or losses in BCOR (gene encoding the BCL6 corepressor)-frameshift (n=3), nonsense (n=2), splicing site (n=1), and copy number loss (n=4)- were identified in 10/42 splenic diffuse Red Pulp lymphoma (24%), whereas only one frameshift mutation was identified in 46 splenic marginal zone lymphoma cases (2%). Inversely, KLF2, TNFAIP3 and MYD88 mutations were rare (one KLF2 mutant out of 42 samples; 2%) or absent (TNFAIP3 and MYD88) in splenic diffuse Red Pulp lymphoma compaRed to splenic marginal zone lymphoma. These findings define an original genetic profile of splenic diffuse Red Pulp lymphoma, suggesting distinct mechanisms of pathogenesis from splenic marginal zone lymphoma and hairy-cell leukaemia.
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Splenic diffuse Red Pulp lymphoma has a distinct pattern of somatic mutations amongst B-cell malignancies.
Leukemia & lymphoma, 2016Co-Authors: Alexandra Traverse-glehen, Sophie Gazzo, Aurelie Verney, Martine Ffrench, Evelyne Callet-bauchu, Laurent Jallades, Kaddour Chabane, Sandrine Hayette, Bertrand Coiffier, Pascale FelmanAbstract:Splenic Diffuse Red Pulp Lymphoma (SDRPL) has been recently introduced as a provisional entity but differential diagnosis with other splenic lymphomas is needed to be clarified since the therapeutic approaches are distinct. Recently described recurrent mutations or CD180 expression appear useful for differential diagnosis. We completed our previous description in a larger cohort including 53 patients selected on the presence of characteristic villous cells in peripheral blood (PB) and a specific immunophenotype. Immunoglobulin heavy variable (IGHV), BRAF, MYD88, and NOTCH2 mutations were determined and CD180 and BRAF expressions were assessed. Most cases (79%) were IGHV mutated with an overrepresentation of IGHV3-23 (19%) and IGHV4-34 (21%). MYD88 L265P and NOTCH2 mutations were observed in one case each, whereas no BRAF V600E mutation or expression was found. All cases demonstrated a high CD180 expression. Those results strengthen the concept that SDRPL does emerge as a new lymphoma entity distinct from the other splenic lymphomas with circulating lymphocytes.
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Relevance of a scoring system including CD11c expression in the identification of splenic diffuse Red Pulp small B-cell lymphoma (SRPL)
Hematological Oncology, 2011Co-Authors: Lucile Baseggio, Dominique Morel, Jean-pierre Magaud, Alexandra Traverse-glehen, Evelyne Callet-bauchu, Françoise Berger, Gilles Salles, Pascale FelmanAbstract:Splenic Red Pulp lymphoma with numerous basophilic villous lymphocytes' (SRPL), recently described, is characterized by clinical, morphologic, immunologic, cytogenetic and molecular features distinct from SMZL/SLVL and HCL. In particular, the intensity of CD11c staining (expressed as fluorescence intensity -RFI-) in SRPL is significantly different from the RFI in SMZL/SLVL and HCL. Moreover the use of a scoring system based on the expression of CD11c, CD22, CD76, CD38 and CD27 appears to improve the differential diagnosis between SRPL and SMZL/SLVL and emphasizes that SRPL is an entity closed to but distinct from SMZL/SLVL. Copyright © 2010 John Wiley & Sons, Ltd.
