scholarly journals VILLOUS LYMPHOCYTES IN BLOOD AND BONE MARROW IN SOME FORMS OF B-CELL LYMPHOID MALIGNANCIES

2020 ◽  
pp. 29-33
Author(s):  
Alyona Polishchuk ◽  
Michael Zavelevich ◽  
Daniil Gluzman
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Hairy Cell Leukemia ◽  
Marginal Zone ◽  
Marginal Zone Lymphoma ◽  
Splenic Marginal Zone Lymphoma ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Trap Activity ◽  
Red Pulp

The cytological and immunocytochemical features of the lymphocytes with villous morphology in peripheral blood and bone marrow in some B-lymphoproliferative disorders were studied. The diagnosis of hairy cell leukemia, a hairy cell leukemia variant, splenic marginal zone lymphoma and splenic diffuse red pulp small B-cell lymphoma was ascertained in accordance with the new revision of the WHO classification (2016). The neoplastic cells of hairy cell leukemia were determined by the presence of high tartrate resistant acid phosphatase (TRAP) activity. Cell surface expression of CD19, CD20 and CD21 antigens was detected. Also, the expression of CD25, CD103 and CD200, and in some cases cyclin D1, was found out. CD5, CD10 and CD23 were not detected. The immunophenotype of cells in splenic marginal zone lymphoma with villous processes also corresponded to the mature B cells. The expression of CD19, CD20 and CD21 was observed in all cases, CD11c – in 50% of patients, CD25 or CD5 – in 10% of patients. In 80% of patients, the pathologic cells did not show TRAP activity. In the bone marrow and peripheral blood cells of patients with diffuse red pulp lymphoma, TRAP activity was not detected. An immunophenotype in the hairy cell leukemia variant was different from those of classic HCL (CD19+CD20+CD22+CD103+CD11c+CD5–CD10–CD23–). Characterized immunophenotypical markers, which have differential diagnostic values in several forms of lymphoid tumors of B cell origin, will be important for the choice of treatment methods and prognosis

scholarly journals CD5-Negative, CD10-Negative Low-Grade B-Cell Lymphoproliferative Disorders of the Spleen

2021 ◽  
Vol 28 (6) ◽  
pp. 5124-5147
Author(s):  
John J. Schmieg ◽  
Jeannie M. Muir ◽  
Nadine S. Aguilera ◽  
Aaron Auerbach
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Hairy Cell Leukemia ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Lymphoproliferative Disorders ◽  
Low Grade ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Red Pulp

CD5-negative, CD10-negative low-grade B-cell lymphoproliferative disorders (CD5-CD10-LPD) of the spleen comprise a fascinating group of indolent, neoplastic, mature B-cell proliferations that are essential to accurately identify but can be difficult to diagnose. They comprise the majority of B-cell LPDs primary to the spleen, commonly presenting with splenomegaly and co-involvement of peripheral blood and bone marrow, but with little to no involvement of lymph nodes. Splenic marginal zone lymphoma is one of the prototypical, best studied, and most frequently encountered CD5-CD10-LPD of the spleen and typically involves white pulp. In contrast, hairy cell leukemia, another well-studied CD5-CD10-LPD of the spleen, involves red pulp, as do the two less common entities comprising so-called splenic B-cell lymphoma/leukemia unclassifiable: splenic diffuse red pulp small B-cell lymphoma and hairy cell leukemia variant. Although not always encountered in the spleen, lymphoplasmacytic lymphoma, a B-cell lymphoproliferative disorder consisting of a dual population of both clonal B-cells and plasma cells and the frequent presence of the MYD88 L265P mutation, is another CD5-CD10-LPD that can be seen in the spleen. Distinction of these different entities is possible through careful evaluation of morphologic, immunophenotypic, cytogenetic, and molecular features, as well as peripheral blood and bone marrow specimens. A firm understanding of this group of low-grade B-cell lymphoproliferative disorders is necessary for accurate diagnosis leading to optimal patient management.

Gene Expression Profiling Classifies Splenic Marginal Zone Lymphoma and Hairy Cell Leukemia-Variant as Related Diseases That Are Distinct From Typical Hairy Cell Leukemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3467-3467
Author(s):  
Sarah L Hockley ◽  
Alison Morilla ◽  
Andrew Wotherspoon ◽  
Brian A Walker ◽  
Nicholas J Dickens ◽  
...  
Keyword(s):  
Gene Expression ◽  
B Cell ◽  
Hairy Cell Leukemia ◽  
Marginal Zone ◽  
Expression Profiles ◽  
Splenic Marginal Zone Lymphoma ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Transcription Profiles ◽  
Insight Into

Abstract Abstract 3467 Poster Board III-355 Hairy cell leukemia (HCL) is an uncommon B-cell malignancy that shares some features with a variant form, HCL-variant, and splenic marginal zone lymphoma (SMZL). The distinction between these disorders can be difficult, but correct diagnosis is important for patient management and clinical outcome. The recent WHO classification has recognized SMZL as a distinct entity and HCL-variant was included in a provisional category of unclassifiable splenic lymphomas involving the splenic red pulp that also includes splenic diffuse red pulp small B-cell lymphoma (SDSL). The molecular features of these disorders are still largely uncharacterized and genomic studies have been limited due to their rarity. We have used Affymetrix gene expression microarrays to compare the transcription profiles of 31 HCL, 24 HCL-variant, 44 SMZL and 5 cases of SDSL with the aim of elucidating the relationships between these disorders and to identify novel potential therapeutic and disease-specific diagnostic targets. Total RNA was extracted from PBMC samples enriched for tumor cells (median 89%, range 70-98%) and the expression of approximately 18,000 genes was interrogated using the Affymetrix Human Exon 1.0 ST Array. Data were normalized and analyzed using Partek Genomics Suite® and differentially expressed transcripts between the disorders were identified by ANOVA. Unsupervised hierarchical clustering revealed disease-related patterns within the transcription profiles. Strikingly, the HCL-variant, SMZL and SDSL profiles clustered together and separately from those of typical HCL. Using a false discovery rate threshold of <0.001 and an expression fold-change >2 we identified 366 transcripts that distinguished HCL from HCL-variant, SMZL and SDSL. Using these same criteria, and even those less stringent, we could not identify a gene expression signature that could distinguish between HCL-variant, SMZL and SDSL. Biological interpretation of the data revealed many of the differentially expressed transcripts linked to immune response and signal transduction processes, including key oncogenes and tumor suppressor genes. Transcripts with higher expression in HCL-variant, SMZL and SDSL relative to HCL were associated with lymphocyte activation and proliferation, NFκB signaling and integrin signaling. Conversely, transcripts with higher expression in HCL relative to HCL-variant, SMZL and SDSL, comprised amongst others, pathways of antigen processing, MAP kinase signaling, JAK-STAT signaling, and FLT3 signaling. Comparison of the transcription signatures of HCL, HCL-variant and SMZL provides insight into their relationships and for the first time provides strong evidence that HCL-variant and SDSL may be variant forms of SMZL and that HCL remains as a distinct disease entity characterized by different signaling pathways. These data further strengthen our previous observation that showed that the immunoglobulin heavy chain gene (IGH) repertoire of HCL-variant is more similar to SMZL than to HCL and that, in contrast to HCL, both HCL-variant and SMZL contain subsets of cases with unmutated IGHV. Interestingly, the expression profiles of both HCL-variant and SMZL could not be discriminated based on their IGHV mutation status. We are currently performing further analyses of these data, including comparison with the expression profiles of normal B cells, with the aim of gaining further insight into the clonal history and the normal B-cell counterpart of these disorders. Disclosures No relevant conflicts of interest to declare.

BRAF and MAP2K1 Genes Mutation in Splenic Marginal Zone Lymphoma and Hairy Cell Leukemia

2016 ◽  
Vol 16 ◽  
pp. S99-S100
Author(s):  
Hunan Julhakyan ◽  
Igor Yakutik ◽  
Lyubov Al-Radi ◽  
Bella Biderman ◽  
Tatyana Moiseeva ◽  
...  
Keyword(s):  
Hairy Cell Leukemia ◽  
Marginal Zone ◽  
Marginal Zone Lymphoma ◽  
Splenic Marginal Zone Lymphoma ◽  
Hairy Cell ◽  
Cell Leukemia

Different IGH Rearrangement and Somatic Hypermutation Patterns in Hairy-Cell Leukemia, Hairy-Cell Leukemia Variant and Splenic Marginal Zone Lymphoma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2082-2082 ◽  
Author(s):  
Sarah L. Hockley ◽  
Stavroula Giannouli ◽  
Alison Morilla ◽  
Gareth J. Morgan ◽  
Estella Matutes ◽  
...  
Keyword(s):  
Hairy Cell Leukemia ◽  
Marginal Zone ◽  
Somatic Hypermutation ◽  
Gene Segment ◽  
Marginal Zone Lymphoma ◽  
Splenic Marginal Zone Lymphoma ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Purine Analogues ◽  
Igh Rearrangement

Abstract Hairy cell leukemia (HCL) and its variant form (HCL-v) are rare B-cell disorders, with different and distinct morphology, immunophenotype, clinical behaviour and response to treatment. HCL-v patients do not respond to purine analogues and have a median survival of seven years compared to over 20 years in HCL, a disease potentially curable with purine analogues in up to 80% of cases. Despite these differences, the resemblance between these two malignancies and splenic marginal zone lymphoma (SMZL) has led to the suggestion that they all may share a common clonal progenitor that homes within the marginal zone of the splenic white pulp. Since the study of immunoglobulin heavy chain gene (IGH) rearrangements provides crucial information regarding the differentiation stages at which particular B-cells are transformed, we have investigated the configuration of the IGH genes in a series of well defined HCL (n=17), HCL-v (n=28) and SMZL (n=82) samples. VDJH rearrangements were PCR-amplified and sequenced using an automated 3130xL sequencer (ABI). The sequences obtained were compared to the closest germline segments using the IMGT database (http://imgt.cines.fr) in order to study the level of somatic hypermutation as well as gene segment usage and CDR3 composition in IGH rearrangements. We were able to amplify a functional VDJH rearrangement in all 127 cases. A significant proportion of SMZL (31/82; 38%) and HCL-v (7/28; 25%) cases were found to be unmutated (range: 0–1.8%). In contrast, all but one HCL cases 16/17 (94%) showed more than 2% deviation from the germline sequence. This suggests that HCL-v is more similar to SMZL than HCL with respect to IGH mutational status. There was a significant over-representation of the VH1 family in the SMZL cases (38%; p&lt;0.01). Regarding specific VH gene segment usage, VH1-02 and V4-34 were significantly over-represented in the SMZL group (28% and 12%, respectively; p&lt;0.001). This was especially striking in the unmutated SMZL cases, the majority (20/31; 64%) using either V4-34 or V1-02. Regarding specific VH segment usage, those SMZL cases carrying a VH1-02 rearrangement showed a similar CDR3 length and composition, with an average isoelectric point of 10.5, and 43% of these cases associated with DH3-03 usage. Within the HCL-v group, there was a significant over-representation of the VH4 family (39%; p&lt;0.001). VH4-34 and VH4-59 were significantly over-represented (18% and 11%, respectively; p&lt;0.001), and mainly restricted to the unmutated cases, 71% of them using VH4-34 or VH4-59. In contrast, there was no significant over-representation of any VH family or gene segment in the typical HCL cases. CONCLUSIONS: Our findings show that in SMZL specific VDJH stereotypes can be identified, likely as a consequence of antigen interaction, which are not present in HCL or HCL-v. Furthermore, HCL-v shares more similarities with SMZL, in terms of IGH rearrangement and somatic hypermutation patterns, than with typical HCL and suggest that different processes occur in the pathogenesis of these three disorders. The clinical implications of these findings are being addressed.

scholarly journals BRAF V600E and MAP2K1 Mutations in Hairy Cell Leukemia and Splenic Marginal Zone Lymphoma Cases

2015 ◽  
Vol 35 (2) ◽  
pp. 257-259 ◽  
Author(s):  
Sang-Yong Shin ◽  
Seung-Tae Lee ◽  
Hee-Jin Kim ◽  
Chang-Seok Ki ◽  
Chul Won Jung ◽  
...  
Keyword(s):  
Hairy Cell Leukemia ◽  
Marginal Zone ◽  
Marginal Zone Lymphoma ◽  
Braf V600e ◽  
Splenic Marginal Zone Lymphoma ◽  
Hairy Cell ◽  
Cell Leukemia

scholarly journals VH gene analysis of hairy cell leukemia reveals a homogeneous mutation status and suggests its marginal zone B-cell origin

Leukemia ◽  
2004 ◽  
Vol 18 (10) ◽  
pp. 1729-1732 ◽  
Author(s):  
V Vanhentenrijk ◽  
A Tierens ◽  
I Wlodarska ◽  
G Verhoef ◽  
C D Wolf-Peeters
Keyword(s):  
B Cell ◽  
Hairy Cell Leukemia ◽  
Marginal Zone ◽  
Gene Analysis ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Mutation Status ◽  
Vh Gene

scholarly journals Genomics of Hairy Cell Leukemia

2017 ◽  
Vol 35 (9) ◽  
pp. 1002-1010 ◽  
Author(s):  
Enrico Tiacci ◽  
Valentina Pettirossi ◽  
Gianluca Schiavoni ◽  
Brunangelo Falini
Keyword(s):  
B Cell ◽  
Hairy Cell Leukemia ◽  
Ex Vivo ◽  
Braf Inhibitor ◽  
Braf V600e ◽  
Leukemic Cells ◽  
Splenic Marginal Zone Lymphoma ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Purine Analogs

Hairy cell leukemia (HCL) is a chronic mature B-cell neoplasm with unique clinicopathologic features and an initial exquisite sensitivity to chemotherapy with purine analogs; however, the disease relapses, often repeatedly. The enigmatic pathogenesis of HCL was recently clarified by the discovery of its underlying genetic cause, the BRAF-V600E kinase-activating mutation, which is somatically and clonally present in almost all patients through the entire disease spectrum and clinical course. By aberrantly activating the RAF-MEK-ERK signaling pathway, BRAF-V600E shapes key biologic features of HCL, including its specific expression signature, hairy morphology, and antiapoptotic behavior. Accompanying mutations of the KLF2 transcription factor or the CDKN1B/p27 cell cycle inhibitor are recurrent in 16% of patients with HCL and likely cooperate with BRAF-V600E in HCL pathogenesis. Conversely, BRAF-V600E is absent in other B-cell neoplasms, including mimickers of HCL that require different treatments (eg, HCL-variant and splenic marginal zone lymphoma). Thus, testing for BRAF-V600E allows for a genetics-based differential diagnosis between HCL and HCL-like tumors, even noninvasively in routine blood samples. BRAF-V600E also represents a new therapeutic target. Patients’ leukemic cells exposed ex vivo to BRAF inhibitors are spoiled of their HCL identity and then undergo apoptosis. In clinical trials of patients with HCL who have experienced multiple relapses after purine analogs or who are refractory to purine analogs, a short course of the oral BRAF inhibitor vemurafenib produced an almost 100% response rate, including complete remission rates of 35% to 42%, without myelotoxicity. To further improve on these results, it will be important to clarify the mechanisms of incomplete leukemic cell eradication by vemurafenib and to explore chemotherapy-free combinations of a BRAF inhibitor with other targeted agents (eg, a MEK inhibitor and/or an anti-CD20 monoclonal antibody).

Comparison of IgH Gene Rearrangement Configuration between Hairy Cell Leukemia (HCL) and Hairy Cell Leukemia Variant (HCL-v).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4997-4997
Author(s):  
David Gonzalez ◽  
Ricardo Morilla ◽  
Alison Morilla ◽  
Monica Else ◽  
Nnenna Osuji ◽  
...  
Keyword(s):  
Gene Expression ◽  
B Cells ◽  
Hairy Cell Leukemia ◽  
Marginal Zone ◽  
Gene Segment ◽  
Variant Form ◽  
Splenic Marginal Zone Lymphoma ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Mutational Status

Abstract Hairy cell leukemia (HCL) is a rare B-cell disorder, with a variant form, which differs from the former in clinical behaviour, morphology and immunophenotype. The resemblance of these malignancies to splenic marginal zone lymphoma (SMZL), has led to the suggestion that they may share a common clonal progenitor that homes within the marginal zone of the splenic germinal centres. The immunophenotype and recent global gene expression results offer some support for this view, with a similar profile seen in HCL, and a subset of memory B-cells that are localized to the marginal zone. However, studies of the mutational status of the Ig genes are controversial. The majority of HCL cases are mutated, whereas up to 30% of SMZL cases are unmutated. Further investigation to understand these differences and to identify the cell of origin in these disorders is needed. In addition, there are no data on gene expression or VH mutation in HCL-variant (HCL-v), an entity with a poorer outcome and for which there is as yet no effective therapy. We have analysed a series of 13 HCL and 23 HCL-v, for the configuration of the Ig heavy chain rearrangements. VDJH rearrangements were PCR-amplified and sequenced using an automated 3130xL sequencer (Applied Biosystems, Warrington, UK). The sequences obtained were compared to the closest germline segments using V-base (CRI, Cambridge, UK) in order to study the level of somatic hypermutation as well as gene segment usage in IgH rearrangements. The majority of the HCL (92%) showed more than 2% deviation from the closest germline VH gene segment, compared to only 17/23 (74%) in the HCL-v cases. In the mutated cases, the percentage of mutation was similar for HCL and HCL-v (mean 5.8% and 5.9%, respectively), and none of the cases appeared to show ongoing hypermutation. Within the HCL-v group, 4 out of the 6 unmutated cases used VH4-34 segment, and the remaining 2 used VH1-03. Both genes are known to be associated with autoimmune diseases, and they are excluded from the normal and malignant memory plasma cell repertoires. Also, JH5 segment was found in 47% of the HCL-v, while it was absent in the HCL repertoire. This finding is particularly interesting, as JH5 segment is normally under-represented in most normal and malignant B-cells, except for a characteristic group of IgG-expressing chronic lymphocytic leukemias. Our data suggest that HCL-v is, unlike HCL, heterogeneous regarding IgVH mutations, but has restricted IgH repertoire that, at least in some cases, might be derived from activated, self-reactive B-lymphocytes that have not experienced the germinal-centre reaction.

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