scholarly journals Association of bcl-1 rearrangements with lymphocytic lymphoma of intermediate differentiation

Blood ◽  
1990 ◽  
Vol 76 (10) ◽  
pp. 2086-2090 ◽  
Author(s):  
LJ Medeiros ◽  
JH Van Krieken ◽  
ES Jaffe ◽  
M Raffeld
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Chromosomal Translocation ◽  
B Cell Lymphoma ◽  
Distinct Type ◽  
Lymphocytic Leukemia ◽  
Chain Gene ◽  
Low Grade ◽  
Chromosome 11 ◽  
Follicular Lymphomas

Abstract Previous studies using classical cytogenetics have demonstrated the presence of the t(11;14) (q13;q32) chromosomal translocation in some cases of lymphocytic lymphoma of intermediate differentiation (IDL), a distinct type of low grade B-cell lymphoma. This finding suggested that the bcl-1 region (located at band q13 of chromosome 11) might be involved in this neoplasm. Using a genomic probe from the major breakpoint area of the bcl-1 locus, we identified rearrangements of the bcl-1 region in 10 of 19 cases, 2 of which comigrated with a rearranged allele of the immunoglobulin heavy chain gene joining region. In contrast, bcl-1 rearrangements were not found in other types of low grade B-cell lymphoma, specifically in 36 cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and 27 cases of follicular lymphoma (FL). To further assess the molecular pathology of IDL, we analyzed these cases for rearrangements of the bcl-2 proto- oncogene, which is associated primarily with follicular lymphomas. None of the 19 cases of IDL had rearrangements. Furthermore, none of the 36 cases of CLL/SLL showed bcl-2 rearrangements, whereas, as expected, 21 of 27 cases of FL had rearrangements of the bcl-2 locus. Our findings demonstrate an association between a rearranged bcl-1 region with approximately 50% of IDLs and suggest that abnormalities of this locus may be important in the pathogenesis of IDL.

scholarly journals Association of bcl-1 rearrangements with lymphocytic lymphoma of intermediate differentiation

Blood ◽  
1990 ◽  
Vol 76 (10) ◽  
pp. 2086-2090 ◽  
Author(s):  
LJ Medeiros ◽  
JH Van Krieken ◽  
ES Jaffe ◽  
M Raffeld
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Chromosomal Translocation ◽  
B Cell Lymphoma ◽  
Distinct Type ◽  
Lymphocytic Leukemia ◽  
Chain Gene ◽  
Low Grade ◽  
Chromosome 11 ◽  
Follicular Lymphomas

Previous studies using classical cytogenetics have demonstrated the presence of the t(11;14) (q13;q32) chromosomal translocation in some cases of lymphocytic lymphoma of intermediate differentiation (IDL), a distinct type of low grade B-cell lymphoma. This finding suggested that the bcl-1 region (located at band q13 of chromosome 11) might be involved in this neoplasm. Using a genomic probe from the major breakpoint area of the bcl-1 locus, we identified rearrangements of the bcl-1 region in 10 of 19 cases, 2 of which comigrated with a rearranged allele of the immunoglobulin heavy chain gene joining region. In contrast, bcl-1 rearrangements were not found in other types of low grade B-cell lymphoma, specifically in 36 cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and 27 cases of follicular lymphoma (FL). To further assess the molecular pathology of IDL, we analyzed these cases for rearrangements of the bcl-2 proto- oncogene, which is associated primarily with follicular lymphomas. None of the 19 cases of IDL had rearrangements. Furthermore, none of the 36 cases of CLL/SLL showed bcl-2 rearrangements, whereas, as expected, 21 of 27 cases of FL had rearrangements of the bcl-2 locus. Our findings demonstrate an association between a rearranged bcl-1 region with approximately 50% of IDLs and suggest that abnormalities of this locus may be important in the pathogenesis of IDL.

scholarly journals An Interesting Case of Lineage Switch to Histiocytic Sarcoma in a Case of Diffuse Large B Cell Lymphoma

2019 ◽  
Vol 05 (02) ◽  
pp. 093-096
Author(s):  
Manasi C. Mundada ◽  
Faiq Ahmed ◽  
Sudha Murthy ◽  
Krishna Mohan Mallavarapu
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Histiocytic Sarcoma ◽  
Lymphocytic Leukemia ◽  
Low Grade ◽  
Phenotypic Characteristics ◽  
Lineage Switch ◽  
Large B Cell Lymphoma ◽  
Large B Cell

AbstractLineage switch involves change in the phenotypic characteristics from one type to another. It is a rare phenomenon described in mature lymphoid neoplasms which transform to histiocytic/dendritic cell tumor, more commonly described in low-grade lymphoma like follicular, chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), wherein the neoplasm loses the phenotypic characteristics of non-Hodgkin lymphoma and acquires the markers of histiocytic differentiation. Here, we present a case of diffuse large B cell lymphoma transforming to histiocytic sarcoma post 6 months of start of therapy. Histiocytic sarcoma being a very aggressive tumor, the patient had a very rapid deteriorating course and succumbed to disease.

Inactivation of the p16 Cyclin-Dependent Kinase Inhibitor in High-Grade Canine Non-Hodgkin's T-Cell Lymphoma

2007 ◽  
Vol 44 (4) ◽  
pp. 467-478 ◽  
Author(s):  
S. P. Fosmire ◽  
R. Thomas ◽  
C. M. Jubala ◽  
J. W. Wojcieszyn ◽  
V. E. O. Valli ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
T Cell Lymphoma ◽  
World Health ◽  
Low Grade ◽  
High Grade ◽  
Chromosome 11 ◽  
Rb Phosphorylation

The significance of p16/Rb tumor suppressor pathway inactivation in T-cell non-Hodgkin's lymphoma (NHL) remains incompletely understood. We used naturally occurring canine NHL to test the hypothesis that p16 inactivation has specific pathologic correlates. Forty-eight samples (22 T-cell NHL and 26 B-cell NHL) were included. As applicable, metaphase- or array-based comparative genomic hybridization, Southern blotting, promoter methylation, and Rb phosphorylation were used to determine the presence, expression, and activity of p16. Fisher's exact test was used to test for significance. Deletion of p16 (or loss of dog chromosome 11) was restricted to high-grade T-cell NHL (lymphoblastic T-cell lymphoma and peripheral T-cell lymphoma, not otherwise specified). These were characterized by a concomitant increase of tumor cells with Rb phosphorylation at canonical CDK4 sites. Rb phosphorylation also was seen in high-grade B-cell NHL (diffuse large B-cell lymphoma and Burkitt-type lymphoma), but in those cases, it appeared to be associated with c-Myc overexpression. The data show that p16 deletion or inactivation occurs almost exclusively in high-grade T-cell NHL; however, alternative pathways can generate functional phenotypes of Rb deficiency in low-grade T-cell NHL and in high-grade B-cell NHL. Both morphologic classification according to World Health Organization criteria and assessment of Rb phosphorylation are prognostically valuable parameters for canine NHL.

Detection of t(11;18)(q21;q21) by interphase fluorescence in situ hybridization using API2 and MLTspecific probes

Blood ◽  
2000 ◽  
Vol 96 (6) ◽  
pp. 2215-2218 ◽  
Author(s):  
Judith Dierlamm ◽  
Mathijs Baens ◽  
Margarita Stefanova-Ouzounova ◽  
Kristina Hinz ◽  
Iwona Wlodarska ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
B Cell ◽  
Fluorescence In Situ Hybridization ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Low Grade ◽  
Chromosome 11 ◽  
Interphase Nuclei ◽  
Large B Cell

Abstract The translocation of chromosome 11, long arm, region 2, band 1, to chromosome 18, long arm, region 2, band 1 (t(11;18)(q21;q21)) represents a recurrent chromosomal abnormality in extranodal marginal zone B-cell lymphoma (MZBCL) of mucosa-associated lymphoid tissue (MALT) type and leads to a fusion of the apoptosis inhibitor-2 (API2) gene on chromosome 11 and the MALT lymphoma-associated translocation (MLT) gene on chromosome 18. A 2-color fluorescence in situ hybridization (FISH) assay, which can be used for the detection of t(11;18) in interphase nuclei and metaphase chromosomes on fresh and archival tumor tissue, was developed. The P1 artificial chromosome (PAC) clone located immediately telomeric to the MLT gene and the PAC clone spanning the API2 gene were differentially labeled and used to visualize the derivative chromosome 11 resulting from t(11;18), as evident by the overlapping or juxtaposed red and green fluorescent signals. The assay was applied to interphase nuclei of 20 cases with nonmalignant conditions and 122 B-cell non-Hodgkin's lymphomas (NHLs). The latter group comprised 20 cases of nodal follicle center cell lymphoma and diffuse large B-cell NHL, 10 cases of gastric diffuse large B-cell lymphoma, 10 cases of hairy cell leukemia, and 82 cases of MZBCL (41 extranodal from various locations, 19 nodal, and 22 splenic MZBCL) including 35 cases with an abnormal karyotype, 2 of which revealed t(11;18). By interphase FISH, t(11;18) was detected in 8 gastrointestinal low-grade MALT-type lymphomas including the 2 cytogenetically t(11;18)+ cases. In the 8 t(11;18)+ cases, the FISH results were confirmed by reverse transcriptase–polymerase chain reaction (RT-PCR) usingAPI2 and MLT specific primers. Our results indicate that t(11;18)(q21;q21) specifically characterizes a subgroup of low-grade MZBCL of the MALT-type and that the FISH assay described here is a highly specific and rapid test for the detection of this translocation.

scholarly journals Apoptotic Blocks in Primary Non-Hodgkin B Cell Lymphomas Identified by BH3 Profiling

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1002
Author(s):  
Ryan N. Rys ◽  
Claudia M. Wever ◽  
Dominique Geoffrion ◽  
Christophe Goncalves ◽  
Artin Ghassemian ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Poor Response ◽  
Lymphocytic Leukemia ◽  
Low Grade ◽  
High Grade ◽  
Microtubule Inhibitors ◽  
Mantle Cell ◽  
Induced Apoptosis

To determine causes of apoptotic resistance, we analyzed 124 primary B cell NHL samples using BH3 profiling, a technique that measures the mitochondrial permeabilization upon exposure to synthetic BH3 peptides. Our cohort included samples from chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), high-grade B cell lymphoma with translocations in MYC and BCL2 (HGBL-DH), mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL). While a large number of our samples displayed appropriate responses to apoptosis-inducing peptides, pro-apoptotic functional defects, implicating BAX, BAK, BIM or BID, were seen in 32.4% of high-grade NHLs (12/37) and in 3.4% of low-grade NHLs (3/87, p < 0.0001). The inhibition of single anti-apoptotic proteins induced apoptosis in only a few samples, however, the dual inhibition of BCL2 and MCL1 was effective in 83% of samples, indicating MCL1 was the most common cause of lack of response to the BCL2 inhibitor, venetoclax. We then profiled Toledo and OCI-Ly8 high-grade lymphoma cell lines to determine which drugs could reduce MCL1 expression and potentiate venetoclax responses. Doxorubicin and vincristine decreased levels of MCL1 and increased venetoclax-induced apoptosis (all p < 0.05). Overall, in primary NHLs expressing BCL2 that have no defects in pro-apoptotic signaling, a poor response to venetoclax is primarily due to the presence of MCL1, which may be overcome by combining venetoclax with doxorubicin and vincristine-based chemotherapy or with other anti-microtubule inhibitors.

Detection of t(11;18)(q21;q21) by interphase fluorescence in situ hybridization using API2 and MLTspecific probes

Blood ◽  
2000 ◽  
Vol 96 (6) ◽  
pp. 2215-2218 ◽  
Author(s):  
Judith Dierlamm ◽  
Mathijs Baens ◽  
Margarita Stefanova-Ouzounova ◽  
Kristina Hinz ◽  
Iwona Wlodarska ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
B Cell ◽  
Fluorescence In Situ Hybridization ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Low Grade ◽  
Chromosome 11 ◽  
Interphase Nuclei ◽  
Large B Cell

The translocation of chromosome 11, long arm, region 2, band 1, to chromosome 18, long arm, region 2, band 1 (t(11;18)(q21;q21)) represents a recurrent chromosomal abnormality in extranodal marginal zone B-cell lymphoma (MZBCL) of mucosa-associated lymphoid tissue (MALT) type and leads to a fusion of the apoptosis inhibitor-2 (API2) gene on chromosome 11 and the MALT lymphoma-associated translocation (MLT) gene on chromosome 18. A 2-color fluorescence in situ hybridization (FISH) assay, which can be used for the detection of t(11;18) in interphase nuclei and metaphase chromosomes on fresh and archival tumor tissue, was developed. The P1 artificial chromosome (PAC) clone located immediately telomeric to the MLT gene and the PAC clone spanning the API2 gene were differentially labeled and used to visualize the derivative chromosome 11 resulting from t(11;18), as evident by the overlapping or juxtaposed red and green fluorescent signals. The assay was applied to interphase nuclei of 20 cases with nonmalignant conditions and 122 B-cell non-Hodgkin's lymphomas (NHLs). The latter group comprised 20 cases of nodal follicle center cell lymphoma and diffuse large B-cell NHL, 10 cases of gastric diffuse large B-cell lymphoma, 10 cases of hairy cell leukemia, and 82 cases of MZBCL (41 extranodal from various locations, 19 nodal, and 22 splenic MZBCL) including 35 cases with an abnormal karyotype, 2 of which revealed t(11;18). By interphase FISH, t(11;18) was detected in 8 gastrointestinal low-grade MALT-type lymphomas including the 2 cytogenetically t(11;18)+ cases. In the 8 t(11;18)+ cases, the FISH results were confirmed by reverse transcriptase–polymerase chain reaction (RT-PCR) usingAPI2 and MLT specific primers. Our results indicate that t(11;18)(q21;q21) specifically characterizes a subgroup of low-grade MZBCL of the MALT-type and that the FISH assay described here is a highly specific and rapid test for the detection of this translocation.

scholarly journals Histiocytic Sarcoma: Review, Discussion of Transformation From B-Cell Lymphoma, and Differential Diagnosis

2018 ◽  
Vol 142 (11) ◽  
pp. 1322-1329 ◽  
Author(s):  
Stephanie L. Skala ◽  
David R. Lucas ◽  
Rajan Dewar
Keyword(s):  
Differential Diagnosis ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Histiocytic Sarcoma ◽  
Lymphocytic Leukemia ◽  
Western Hemisphere ◽  
Low Grade ◽  
Small Lymphocytic Lymphoma

Context.— Histiocytic sarcoma is a rare neoplasm of mature histiocytes with an aggressive clinical course that can arise de novo or from a low-grade B-cell lymphoma. In particular, chronic lymphocytic leukemia/small lymphocytic lymphoma is a very common malignancy in the Western hemisphere, and most cases of chronic lymphocytic leukemia/small lymphocytic lymphoma have an indolent course and behavior. However, 2% to 8% of chronic lymphocytic leukemia/small lymphocytic lymphoma cases transform. Histiocytic sarcomatous transformation is rare and portends poor prognosis. Objective.— To review the clinical features, morphology, and key points related to the differential diagnosis for histiocytic sarcoma. We discuss recent understanding of the biology underlying transformation. Data Sources.— University of Michigan case and review of pertinent literature about histiocytic sarcoma and morphologic differential diagnosis. Conclusions.— Histiocytic sarcoma is a rare histiocytic neoplasm that can arise as a result of transdifferentiation from low-grade B-cell lymphomas, and has a wide differential diagnosis including other histiocytic/dendritic cell neoplasms, myeloid neoplasms, lymphomas, melanoma, and carcinoma. However, some key morphologic and immunohistochemical features allow for accurate classification.

Pentostatin Combined with Cyclophosphamide, and Rituximab Induces High Response Rates in Patients with Untreated Indolent B-Cell Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4722-4722
Author(s):  
Felipe Samaniego ◽  
Luis E. Fayad ◽  
Barbara Pro ◽  
Peter McLaughlin ◽  
Maria Alma Rodriguez ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Cell Lymphoma ◽  
Gene Mutations ◽  
B Cell Lymphoma ◽  
Lymphocytic Leukemia ◽  
Chain Gene ◽  
Heavy Chain Gene ◽  
Immunoglobulin Heavy Chain Gene ◽  
Line Therapy

Abstract The addition of rituximab to combination chemotherapy has improved treatment outcomes of indolent lymphomas. Combination therapy with purine analogs, akylating agents, and monoclonal antibodies is a promising approach for treating indolent B-cell lymphoma. Nucleoside analog-based regimens selectively target lymphoid cells, making them attractive drugs for lymphoid cancers. Pentostatin is a nucleoside analog that compared with other nucleoside analogs appears to have less bone marrow cell toxicity. The combination of pentostatin, cyclophosphamide, and rituximab (PCR) is an effective regimen for relapsed chronic lymphocytic leukemia and relapsed indolent B-cell lymphoma. In this study, we examined the efficacy of pentostatin, cyclophosphamide, and rituximab for the treatment of B-cell lymphoma. Pentostatin (4 mg/m2), cyclophosphamide (600 mg/m2), and rituximab (375 mg/m2) were given on day 1 of a 21-day cycle with restaging after every 3 cycles. Patients received prophylaxis with acyclovir 400 mg/po bid and trimethoprim-sulfamethoxazole 3 times per week. Small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL), was stained for ZAP70 staining and immunoglobulin heavy chain gene mutations. At the time of abstract submission, 29 patients are eligible for response and toxicity. There were 12 patients with follicular lymphoma, 13 with SLL/CLL, and 4 with mucosa-associated lymphoid tissue (MALT), and the median age was 63 years. This regimen was used as first-line therapy for 26 patients and second-line therapy in 3 patients. We observed an overall response of 27 out of 29 (93%), CR/CRu in 19 out of 29 (65%), PR in 8 out of 29 (27%), and mixed response in 2 out of 29 (7%). The main toxicities were nausea and vomiting. No prolonged pancytopenia or myelodysplasia were observed. The correlation of ZAP70 and immunoglobulin heavy chain gene mutations with response is ongoing. Our preliminary data demonstrate that PCR therapy is an effective regimen in previously untreated indolent lymphoma.

scholarly journals Notch activation is pervasive in SMZL and uncommon in DLBCL: implications for Notch signaling in B-cell tumors

2021 ◽  
Vol 5 (1) ◽  
pp. 71-83
Author(s):  
Vignesh Shanmugam ◽  
Jeffrey W. Craig ◽  
Laura K. Hilton ◽  
Matthew H. Nguyen ◽  
Christopher K. Rushton ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Lymphocytic Leukemia ◽  
Low Grade ◽  
Tumor Microenvironments ◽  
Notch Intracellular Domain ◽  
Marginal Zones ◽  
Notch Activation

Abstract Notch receptors participate in a signaling pathway in which ligand-induced proteolysis frees the Notch intracellular domain (NICD), allowing it to translocate to the nucleus, form a transcription complex, and induce target gene expression. Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), splenic marginal zone B-cell lymphoma (SMZL), and distinct subsets of diffuse large B-cell lymphoma (DLBCL) are strongly associated with mutations in the 3′ end of NOTCH1 or NOTCH2 that disrupt a proline, glutamic acid, serine, and threonine (PEST) degron domain and stabilize NICD1 and NICD2. By contrast, mutations leading to constitutive Notch activation are rare in primary B-cell neoplasms, suggesting that Notch activation is confined to ligand-rich tumor microenvironments, or that cryptic strong gain-of-function mutations have been missed in prior analyses. To test these ideas, we used immunohistochemical stains to screen a broad range of B-cell tumors for Notch activation. Our analyses reveal that among small B-cell neoplasms, NICD2 is primarily detected in SMZL and is a common feature of both NOTCH2 wild-type and NOTCH2-mutated SMZLs, similar to prior findings with NOTCH1 in CLL/SLL. The greatest NOTCH2 activation was observed in NOTCH2-mutated SMZLs, particularly within splenic marginal zones. By contrast, little evidence of NOTCH2 activation was observed in DLBCL, even in NOTCH2-mutated tumors, suggesting that selective pressure for NOTCH2 activation is mainly confined to low-grade B-cell neoplasms, whereas DLBCLs with NOTCH1 mutations frequently showed evidence of ongoing NOTCH1 activation. These observations have important implications for the pathogenic role of Notch and its therapeutic targeting in B-cell lymphomas.

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