scholarly journals Lack of Bcl-2 expression in feline follicular lymphomas

2019 ◽  
Vol 31 (6) ◽  
pp. 809-817
Author(s):  
Manfred Henrich ◽  
Anna Bauknecht ◽  
Werner Hecht ◽  
Manfred Reinacher
Keyword(s):  
Follicular Lymphoma ◽  
Single Cells ◽  
Leukemia Virus ◽  
Receptor Gene ◽  
Chromosomal Translocation ◽  
Feline Leukemia Virus ◽  
Immunoglobulin Gene ◽  
Follicular Hyperplasia ◽  
Significant Difference ◽  
Follicular Lymphomas

Bcl-2, an anti-apoptotic protein, is commonly overexpressed in follicular lymphomas in humans. This is usually the result of a chromosomal translocation that transposes the Bcl-2 gene into the immunoglobulin gene locus. The immunohistochemical assessment of this overexpression can be used as a tool for the differentiation of follicular lymphoma and follicular hyperplasia. In cats, little information about the expression of Bcl-2 in follicular lymphoma exists. We investigated 18 follicular lymphomas histologically and immunohistochemically for the expression of Bcl-2, CD3, CD45R, and feline leukemia virus. Clonality was assessed by PCR for antigen receptor gene rearrangements. Although the histology resembled that of their human counterparts, diffuse expression of Bcl-2 within the follicles of the feline lymphomas, as seen in human cases, was not present. Only single cells within the follicles, comparable to the reactive controls, were positive for Bcl-2 expression. The mean survival time of 4.6 y confirmed the indolent character of the tumor. None of the clinical parameters assessed were statistically significant predictors of survival. Furthermore, a statistically significant difference in survival of animals with or without anti-neoplastic therapy was also not demonstrable.

scholarly journals MYC rearrangements in histologically progressed follicular lymphomas

Blood ◽  
1992 ◽  
Vol 80 (3) ◽  
pp. 758-767 ◽  
Author(s):  
T Yano ◽  
ES Jaffe ◽  
DL Longo ◽  
M Raffeld
Keyword(s):  
Follicular Lymphoma ◽  
Molecular Organization ◽  
Aggressive Lymphoma ◽  
Chain Gene ◽  
Low Grade ◽  
Immunoglobulin Gene ◽  
High Grade ◽  
Light Chain Gene ◽  
Myc Gene ◽  
Follicular Lymphomas

Abstract Histologic transformation of low-grade follicular lymphoma to an aggressive-grade lymphoma occurs in 60% to 80% of patients during their clinical course. The events that drive the transformation process are poorly understood. Deregulation of the MYC gene has been implicated in a small number of cases. This observation led us to examine the molecular organization of the MYC oncogene in 38 cases of histologically transformed lymphomas that arose from follicular lymphomas, and in 18 of the initial pretransformation follicular lymphomas. In addition, we examined 58 “control” low-grade follicular lymphomas that had not yet shown evidence of histologic progression. Immunoglobulin heavy chain and light chain gene rearrangements were detected in all biopsies and rearrangements of the BCL-2 locus were seen in 36 of 38 of the transformed lymphomas (consistent with their origin from follicular lymphomas), in 18 of 18 of the pretransformation follicular lymphomas, and in 51 of 58 of the control follicular lymphomas. All 18 pretransformation follicular lymphoma specimens displayed at least one immunoglobulin gene and BCL-2 rearrangement in common with the corresponding histologically progressed lymphoma, indicating a clonal relationship between the original follicular lymphoma and the histologically transformed lymphoma. MYC rearrangements were detected in 3 of 38 (8%) transformed lymphomas and in 1 of 58 (2%) control follicular lymphomas. The latter MYC rearranged follicular lymphoma was clinically aggressive and transformed to a high- grade lymphoma that led to the death of the patient within 20 months. None of the 18 pretransformation follicular lymphomas showed MYC rearrangement, including two from patients who later demonstrated MYC rearrangement in the progressed aggressive lymphoma. PvuII mutational analysis failed to identify additional MYC gene abnormalities in the progressed lymphomas. Because the Epstein-Barr virus (EBV) is associated with a fraction of high-grade lymphomas and is known to upregulate BCL-2, we looked for a potential role for this agent in our progressed lymphomas. We did not detect viral sequences in any case indicating that EBV does not play a major role in progression. The presence of MYC rearrangements in a small fraction of progressed aggressive lymphomas, and not in the corresponding antecedent follicular lymphomas, suggests that acquisition of a MYC rearrangement is in some cases associated with the transformation event.

Follicular lymphomas' BCL-2/IgH junctions contain templated nucleotide insertions: novel insights into the mechanism of t(14;18) translocation

Blood ◽  
2000 ◽  
Vol 95 (11) ◽  
pp. 3520-3529 ◽  
Author(s):  
Ulrich Jäger ◽  
Silke Böcskör ◽  
Trang Le ◽  
Gerlinde Mitterbauer ◽  
Ingrid Bolz ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Follicular Lymphoma ◽  
B Cell ◽  
De Novo ◽  
Chromosomal Translocation ◽  
B Cell Differentiation ◽  
Chromosome 14 ◽  
Complex Process ◽  
Nucleotide Insertions ◽  
Follicular Lymphomas

The human t(14;18) chromosomal translocation is assumed to result from illegitimate rearrangement between BCL-2 and DH/JH gene segments during V(D)J recombination in early B cells. De novo nucleotides are found inserted in most breakpoints and have been thus far interpreted as nontemplated N region additions. In this report, we have analyzed both direct (BCL-2/JH) and reciprocal (DH/BCL-2) breakpoints derived from 40 patients with follicular lymphoma with t(14;18). Surprisingly, we found that more than 30% of the breakpoint junctions contain a novel type of templated nucleotide insertions, consisting of short copies of the surrounding BCL-2, DH, and JH sequences. The features of these templated nucleotides, including multiplicity of copies for 1 template and the occurrence of mismatches in the copies, suggest the presence of a short-patch DNA synthesis, templated and error-prone. In addition, our analysis clearly shows that t(14;18) occurs during a very restricted window of B-cell differentiation and involves 2 distinct mechanisms: V(D)J recombination, mediating the breaks on chromosome 14 during an attempted secondary DH to JH rearrangement, and an additional unidentified mechanism creating the initial breaks on chromosome 18. Altogether, these data suggest that the t(14;18) translocation is a more complex process than previously thought, involving the interaction and/or subversion of V(D)J recombination with multiple enzymatic machineries.

scholarly journals MYC rearrangements in histologically progressed follicular lymphomas

Blood ◽  
1992 ◽  
Vol 80 (3) ◽  
pp. 758-767 ◽  
Author(s):  
T Yano ◽  
ES Jaffe ◽  
DL Longo ◽  
M Raffeld
Keyword(s):  
Follicular Lymphoma ◽  
Molecular Organization ◽  
Aggressive Lymphoma ◽  
Chain Gene ◽  
Low Grade ◽  
Immunoglobulin Gene ◽  
High Grade ◽  
Light Chain Gene ◽  
Myc Gene ◽  
Follicular Lymphomas

Histologic transformation of low-grade follicular lymphoma to an aggressive-grade lymphoma occurs in 60% to 80% of patients during their clinical course. The events that drive the transformation process are poorly understood. Deregulation of the MYC gene has been implicated in a small number of cases. This observation led us to examine the molecular organization of the MYC oncogene in 38 cases of histologically transformed lymphomas that arose from follicular lymphomas, and in 18 of the initial pretransformation follicular lymphomas. In addition, we examined 58 “control” low-grade follicular lymphomas that had not yet shown evidence of histologic progression. Immunoglobulin heavy chain and light chain gene rearrangements were detected in all biopsies and rearrangements of the BCL-2 locus were seen in 36 of 38 of the transformed lymphomas (consistent with their origin from follicular lymphomas), in 18 of 18 of the pretransformation follicular lymphomas, and in 51 of 58 of the control follicular lymphomas. All 18 pretransformation follicular lymphoma specimens displayed at least one immunoglobulin gene and BCL-2 rearrangement in common with the corresponding histologically progressed lymphoma, indicating a clonal relationship between the original follicular lymphoma and the histologically transformed lymphoma. MYC rearrangements were detected in 3 of 38 (8%) transformed lymphomas and in 1 of 58 (2%) control follicular lymphomas. The latter MYC rearranged follicular lymphoma was clinically aggressive and transformed to a high- grade lymphoma that led to the death of the patient within 20 months. None of the 18 pretransformation follicular lymphomas showed MYC rearrangement, including two from patients who later demonstrated MYC rearrangement in the progressed aggressive lymphoma. PvuII mutational analysis failed to identify additional MYC gene abnormalities in the progressed lymphomas. Because the Epstein-Barr virus (EBV) is associated with a fraction of high-grade lymphomas and is known to upregulate BCL-2, we looked for a potential role for this agent in our progressed lymphomas. We did not detect viral sequences in any case indicating that EBV does not play a major role in progression. The presence of MYC rearrangements in a small fraction of progressed aggressive lymphomas, and not in the corresponding antecedent follicular lymphomas, suggests that acquisition of a MYC rearrangement is in some cases associated with the transformation event.

Pediatric Follicular Lymphoma: A Rare Clinicopathologic Entity

2009 ◽  
Vol 133 (1) ◽  
pp. 142-146 ◽  
Author(s):  
Renuka Agrawal ◽  
Jun Wang
Keyword(s):  
Molecular Markers ◽  
Follicular Lymphoma ◽  
Clinical Stage ◽  
Good Prognosis ◽  
Careful Attention ◽  
Aggressive Therapy ◽  
Follicular Hyperplasia ◽  
Favorable Prognosis ◽  
Follicular Lymphomas

Abstract Follicular lymphoma, although common in adults, is rare in children. Pediatric follicular lymphoma has a more favorable prognosis than adult follicular lymphoma, even though it is often of higher grade. Children with follicular lymphomas are generally at a lower clinical stage, respond well to less aggressive therapy, and have a better survival than adults. Follicular lymphoma must be distinguished from reactive follicular hyperplasia, which it may mimic. Immunohistochemical and molecular markers serve to facilitate this distinction, as well as careful attention to clinical and morphologic details. It is important to recognize pediatric follicular lymphoma as a unique clinicopathologic entity to properly diagnose and manage these patients. It may represent a subset of follicular lymphoma with a particularly good prognosis.

Follicular lymphomas' BCL-2/IgH junctions contain templated nucleotide insertions: novel insights into the mechanism of t(14;18) translocation

Blood ◽  
2000 ◽  
Vol 95 (11) ◽  
pp. 3520-3529 ◽  
Author(s):  
Ulrich Jäger ◽  
Silke Böcskör ◽  
Trang Le ◽  
Gerlinde Mitterbauer ◽  
Ingrid Bolz ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Follicular Lymphoma ◽  
B Cell ◽  
De Novo ◽  
Chromosomal Translocation ◽  
B Cell Differentiation ◽  
Chromosome 14 ◽  
Complex Process ◽  
Nucleotide Insertions ◽  
Follicular Lymphomas

Abstract The human t(14;18) chromosomal translocation is assumed to result from illegitimate rearrangement between BCL-2 and DH/JH gene segments during V(D)J recombination in early B cells. De novo nucleotides are found inserted in most breakpoints and have been thus far interpreted as nontemplated N region additions. In this report, we have analyzed both direct (BCL-2/JH) and reciprocal (DH/BCL-2) breakpoints derived from 40 patients with follicular lymphoma with t(14;18). Surprisingly, we found that more than 30% of the breakpoint junctions contain a novel type of templated nucleotide insertions, consisting of short copies of the surrounding BCL-2, DH, and JH sequences. The features of these templated nucleotides, including multiplicity of copies for 1 template and the occurrence of mismatches in the copies, suggest the presence of a short-patch DNA synthesis, templated and error-prone. In addition, our analysis clearly shows that t(14;18) occurs during a very restricted window of B-cell differentiation and involves 2 distinct mechanisms: V(D)J recombination, mediating the breaks on chromosome 14 during an attempted secondary DH to JH rearrangement, and an additional unidentified mechanism creating the initial breaks on chromosome 18. Altogether, these data suggest that the t(14;18) translocation is a more complex process than previously thought, involving the interaction and/or subversion of V(D)J recombination with multiple enzymatic machineries.

scholarly journals Feline Leukemia Virus Detection by ELISA and PCR in Peripheral Blood from 68 Cats with High, Moderate, or Low Suspicion of having FeLV-Related Disease

1996 ◽  
Vol 8 (1) ◽  
pp. 25-30 ◽  
Author(s):  
Marion L. Jackson ◽  
Deborah M. Haines ◽  
Susan M. Taylor ◽  
Vikram Misra
Keyword(s):  
Relative Risk ◽  
Peripheral Blood ◽  
Leukemia Virus ◽  
Feline Leukemia Virus ◽  
Positive Test ◽  
Enzyme Linked Immunosorbent Assay ◽  
Blood Samples ◽  
Related Disease ◽  
Significant Difference ◽  
V Antigen

Clinicopathologic criteria were used to group 68 cats according to high, moderate, or low suspicion of having feline leukemia virus (FeL V)-related disease. Peripheral blood samples were tested for FeL V antigen by enzyme-linked immunosorbent assay (ELISA) and for FeL V DNA by polymerase chain reaction (PCR). There was no significant difference between ELISA and PCR results in the 68 cats. In the high-suspicion group, 46% (11/24) of cytopenic cats were test positive (ELISA and PCR) and 87% (13/15) with hemopoietic neoplasms were test-positive. Also within the high suspicion group, test-positive cats were 2.5 times more likely to die within the 1 year follow-up period than were test-negative (ELISA and PCR) cats. Among cats in the moderate-suspicion group, 15% (2/13) were test-positive, and none (0/16) of the cats in the low suspicion group was test positive. The relative risk of a positive test (ELISA and PCR) in the high suspicion group was 3.7 times that for the moderate-suspicion group and 22.8 times that for the low suspicion group. There was no significant difference in the relative risk of a positive test result between the moderate and low suspicion groups. The results indicate that FeL V detection by PCR can be adapted for diagnostic purposes using peripheral blood samples, however, results do not differ significantly from FeL V ELISA results. Also, a proportion of cats with a high suspicion of having FeL V-related cytopenia and hemopoietic tumors are negative for both circulating FeL V antigen and DNA. These cats may not have FeL V-related disease, or FeL V may exist in a disease-producing but nonreplicating form ultimately detectable by PCR in tissues other than peripheral blood.

scholarly journals Novel markers in pediatric-type follicular lymphoma

2019 ◽  
Vol 475 (6) ◽  
pp. 771-779 ◽  
Author(s):  
Claudio Agostinelli ◽  
Ayse U Akarca ◽  
Alan Ramsay ◽  
Hasan Rizvi ◽  
Manuel Rodriguez-Justo ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Germinal Center ◽  
Diagnostic Marker ◽  
Diagnostic Value ◽  
Molecular Characteristics ◽  
Immunoglobulin Gene ◽  
Follicular Growth ◽  
Follicular Hyperplasia ◽  
Immunohistochemical Markers

Abstract The aim of this study was to review the histopathological, phenotypic, and molecular characteristics of pediatric-type follicular lymphoma (PTFL) and to assess the diagnostic value of novel immunohistochemical markers in distinguishing PTFL from follicular hyperplasia (FH). A total of 13 nodal PTFLs were investigated using immunohistochemistry, fluorescence in situ hybridization (FISH), and PCR and were compared with a further 20 reactive lymph nodes showing FH. Morphologically, PTFL cases exhibited a follicular growth pattern with irregular lymphoid follicles in which the germinal centers were composed of numerous blastoid cells showing a starry-sky appearance. Immunohistochemistry highlighted preserved CD10 (13/13) and BCL6 (13/13) staining, CD20 (13/13) positivity, a K light chain predominance (7/13), and partial BCL2 expression in 6/13 cases (using antibodies 124, E17, and SP66). The germinal center (GC)–associated markers stathmin and LLT-1 were positive in most of the cases (12/13 and 12/13, respectively). Interestingly, FOXP-1 was uniformly positive in PTFL (12/13 cases) in contrast to reactive GCs in FH, where only a few isolated positive cells were observed. FISH revealed no evidence of BCL2, BCL6, or MYC rearrangements in the examined cases. By PCR, clonal immunoglobulin gene rearrangements were detected in 100% of the tested PTFL cases. Our study confirmed the unique morphological and immunophenotypic features of PTFL and suggests that FOXP-1 can represent a novel useful diagnostic marker in the differential diagnosis between PTFL and FH.

scholarly journals Feline Leukemia Virus p27 Antigen Concentration and Proviral DNA Load Are Associated with Survival in Naturally Infected Cats

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 302 ◽  
Author(s):  
Melissa J. Beall ◽  
Jesse Buch ◽  
Genevieve Clark ◽  
Marko Estrada ◽  
Andrei Rakitin ◽  
...  
Keyword(s):  
Point Of Care ◽  
Leukemia Virus ◽  
Microtiter Plate ◽  
Feline Leukemia Virus ◽  
Survival Times ◽  
Antigen Concentration ◽  
Proviral Dna ◽  
Cutoff Values ◽  
Significant Difference ◽  
Highly Correlated

Longitudinal studies of cats naturally infected with feline leukemia virus (FeLV) are important for understanding disease outcomes. Levels of p27 antigen and copy numbers of proviral DNA have been associated with FeLV-infection courses. The purpose of this prospective study was to establish cutoff values for p27 antigen concentration and proviral DNA load that distinguished high positive from low positive groups of cats and to evaluate an association with survival. At enrollment, 254 cats were tested by point-of-care and microtiter plate enzyme-linked immunosorbent assays (ELISAs) for p27 antigen and real-time polymerase chain reaction (PCR) for proviral DNA. The 127 positive cats were retested monthly for six months and monitored for survival over the four-year study. A receiver operating characteristic-based analysis of samples with concordant or discordant qualitative results for p27 antigen and proviral DNA was used to establish cutoff values, and when applied to test results at enrollment for classifying cats as high positive or low positive, a significant difference in survival was observed. High positive cats had a median survival of 1.37 years (95% CI 0.83–2.02) from time of enrollment, while most low positive cats were still alive (93.1% survival). Quantitative results for p27 antigen concentration and proviral DNA load were highly correlated with survival times in FeLV-infected cats.

scholarly journals Identification of Felis catus Gammaherpesvirus 1 in Tsushima Leopard Cats (Prionailurus bengalensis euptilurus) on Tsushima Island, Japan

Viruses ◽  
2018 ◽  
Vol 10 (7) ◽  
pp. 378 ◽  
Author(s):  
Isaac Makundi ◽  
Yushi Koshida ◽  
Yasuyuki Endo ◽  
Kazuo Nishigaki
Keyword(s):  
Dna Sequences ◽  
Leukemia Virus ◽  
Virus Transmission ◽  
Epidemiological Data ◽  
Felis Catus ◽  
Feline Leukemia Virus ◽  
Domestic Cats ◽  
Critically Endangered Species ◽  
Significant Difference ◽  
Prionailurus Bengalensis

Felis catus gammaherpesvirus 1 (FcaGHV1) is a widely endemic infection of domestic cats. Current epidemiological data identify domestic cats as the sole natural host for FcaGHV1. The Tsushima leopard cat (TLC; Prionailurus bengalensis euptilurus) is a critically endangered species that lives only on Tsushima Island, Nagasaki, Japan. Nested PCR was used to test the blood or spleen of 89 TLCs for FcaGHV1 DNA; three (3.37%; 95% CI, 0.70–9.54) were positive. For TLC management purposes, we also screened domestic cats and the virus was detected in 13.02% (95% CI, 8.83–18.27) of 215 cats. Regarding phylogeny, the partial sequences of FcaGHV1 from domestic cats and TLCs formed one cluster, indicating that similar strains circulate in both populations. In domestic cats, we found no significant difference in FcaGHV1 detection in feline immunodeficiency virus-infected (p = 0.080) or feline leukemia virus-infected (p = 0.163) cats, but males were significantly more likely to be FcaGHV1 positive (odds ratio, 5.86; 95% CI, 2.27–15.14) than females. The higher frequency of FcaGHV1 detection in domestic cats than TLCs, and the location of the viral DNA sequences from both cats within the same genetic cluster suggests that virus transmission from domestic cats to TLCs is likely.

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