scholarly journals Deletions involving two distinct regions of 6q in B-cell non-Hodgkin lymphoma

Blood ◽  
1992 ◽  
Vol 80 (7) ◽  
pp. 1781-1787 ◽  
Author(s):  
G Gaidano ◽  
RS Hauptschein ◽  
NZ Parsa ◽  
K Offit ◽  
PH Rao ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Tumor Suppressor Genes ◽  
Molecular Evidence ◽  
Low Grade ◽  
Chromosome 6 ◽  
Tumor Type ◽  
Suppressor Genes ◽  
Non Hodgkin Lymphoma

Abstract The recurrent loss of genetic material from a specific chromosomal region in a given tumor type suggests the presence of a tumor- suppressor gene, the loss or inactivation of which may be relevant for tumorigenesis. In this study, we provide molecular evidence for the recurrent association between deletions on the long arm of chromosome 6 and B-cell non-Hodgkin lymphoma (B-NHL). Normal and tumor DNAs from 71 cases of B-NHL were studied for loss of constitutional heterozygosity (LOH) at 19 loci on chromosome 6 using a panel of restriction fragment length polymorphism (RFLP) probes. LOH, indicating deletion of all or part of 6q, was detected in 16 of 71 cases (22.5%), ranging from low- grade to high-grade B-NHL. The isolated loss of 6p or the loss of other chromosomes (8, 17, 22) tested as controls for specificity was not observed in any case. Comparison of the extent of the deletions among different cases allowed the identification of two distinct regions of minimal deletion (RMD) at 6q25 to 6q27 (RMD-1) and at 6q21 to 6q23 (RMD- 2), respectively, suggesting the existence of two tumor-suppressor genes. These data support a role for 6q deletions in B-NHL pathogenesis and provide a basis for identifying the corresponding tumor-suppressor genes.

scholarly journals Deletions involving two distinct regions of 6q in B-cell non-Hodgkin lymphoma

Blood ◽  
1992 ◽  
Vol 80 (7) ◽  
pp. 1781-1787 ◽  
Author(s):  
G Gaidano ◽  
RS Hauptschein ◽  
NZ Parsa ◽  
K Offit ◽  
PH Rao ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Tumor Suppressor Genes ◽  
Molecular Evidence ◽  
Low Grade ◽  
Chromosome 6 ◽  
Tumor Type ◽  
Suppressor Genes ◽  
Non Hodgkin Lymphoma

The recurrent loss of genetic material from a specific chromosomal region in a given tumor type suggests the presence of a tumor- suppressor gene, the loss or inactivation of which may be relevant for tumorigenesis. In this study, we provide molecular evidence for the recurrent association between deletions on the long arm of chromosome 6 and B-cell non-Hodgkin lymphoma (B-NHL). Normal and tumor DNAs from 71 cases of B-NHL were studied for loss of constitutional heterozygosity (LOH) at 19 loci on chromosome 6 using a panel of restriction fragment length polymorphism (RFLP) probes. LOH, indicating deletion of all or part of 6q, was detected in 16 of 71 cases (22.5%), ranging from low- grade to high-grade B-NHL. The isolated loss of 6p or the loss of other chromosomes (8, 17, 22) tested as controls for specificity was not observed in any case. Comparison of the extent of the deletions among different cases allowed the identification of two distinct regions of minimal deletion (RMD) at 6q25 to 6q27 (RMD-1) and at 6q21 to 6q23 (RMD- 2), respectively, suggesting the existence of two tumor-suppressor genes. These data support a role for 6q deletions in B-NHL pathogenesis and provide a basis for identifying the corresponding tumor-suppressor genes.

Direct Inhibitory Effects of Lenalidomide on the Proliferation and VEGF Production of Non-Hodgkin Lymphoma Cells Are Associated with Increased SPARC Expression

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2612-2612 ◽  
Author(s):  
Ling-Hua Zhang ◽  
Peter H Schafer ◽  
George Muller ◽  
David Stirling ◽  
Blake Bartlett
Keyword(s):  
Cell Proliferation ◽  
Tumor Suppressor ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Tumor Cells ◽  
Cell Lines ◽  
Tumor Suppressor Genes ◽  
Cell Lymphoma ◽  
Suppressor Genes ◽  
Non Hodgkin Lymphoma

Abstract Lenalidomide is an oral anti-angiogenic, anti-proliferative and immunomodulatory drug approved for the treatment of Low- or Intermediate-risk myelodysplastic syndrome associated with a del(5q) cytogenetic abnormality, and in combination with dexamethasone for previously treated multiple myeloma. Early clinical results suggest potential clinical efficacy in B-cell non-Hodgkin lymphoma (NHL). In this study, we investigated lenalidomide-mediated inhibition of cell proliferation and angiogenic factors in the following NHL subtypes: mantle cell lymphoma (MCL), diffuse large-B-cell lymphoma, and follicular lymphoma (FL). The effect of lenalidomide on these tumor cells was determined after 1–3 days of treatment by 3H-thymidine incorporation, Luminex-based microbead array, and real-time qRT-PCR. We also assessed the expression of tumor suppressor genes such as p21cip1 and secreted protein acidic and rich in cysteine (SPARC). We found that lenalidomide induced direct anti-proliferative effects on each NHL subtype, with MCL cells being the most sensitive. Pro-angiogenic factors such as vascular endothelial growth factor (VEGF) were expressed at a high level in all lymphoma cell lines. Lenalidomide inhibited VEGF production at much lower concentrations than required for anti-proliferative effects, particularly in MCL and FL cell lines. Addition of recombinant human VEGF or neutralizing anti-VEGF antibody had no effect on MCL cell proliferation, suggesting that these effects are independent. Mechanistic studies indicated that lenalidomide strongly increased the gene expression of the tumor suppressor genes p21cip1 and SPARC to varying degrees. Elevation of SPARC mRNA significantly correlated with both the anti-proliferative and the VEGF-suppressive effects of lenalidomide on MCL cells (p < 0.05). Transfection of tumor cells with SPARC siRNA led to significant resistance to lenalidomide suggesting that this effect is mediated at least in part through the up-regulation of SPARC. In conclusion, lenalidomide demonstrates anti-proliferative activity against multiple NHL cell subtypes with greatest potency against MCL. The potent anti-VEGF activity of lenalidomide supports the anti-angiogenic potential of the drug. Thus, lenalidomide-induced up-regulation of SPARC mRNA correlates with MCL sensitivity and may have biomarker potential.

E6-Associated Protein (E6-AP): A Potential Tumor Suppressor Protein for Non-Hodgkin Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4336-4336
Author(s):  
Shazia Zafar ◽  
Sathish Srinivasan ◽  
Zafar Nawaz
Keyword(s):  
T Cell ◽  
Tumor Suppressor ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Lymphoid Tissue ◽  
Tumor Suppressor Genes ◽  
Tumor Suppressor Protein ◽  
Non Hodgkin Lymphoma ◽  
T Cell Lymphomas ◽  
Potential Tumor Suppressor

Abstract Over the past decade considerable progress has been made in cloning and characterization of potential tumor suppressor genes. Tumor suppressors have a repressive effect on the regulation of the cell cycle or promote apoptosis and sometimes do both. The function of tumor suppressor proteins fall into several categories, tumor suppressor genes are presumed to encode negative regulator of proliferation and inhibit mitotic activity. Loss of tumor suppressor protein or function of a tumor suppressor protein has been shown to be associated with the cancer formation. Continued investigation into the biochemical and cell biological functions of the tumor suppressor is critical to elucidate the mechanisms by which they normally inhibit proliferation/tumor development and to provide a molecular explanation for their frequent inactivation in cancer. Our laboratory has previously shown that the expression of E6-associated protein (E6-AP), which is an E3 ubiquitin-protein ligase and a coactivator of nuclear hormone receptors, is significantly reduced in human cancers having epithelial cell origin such as breast cancer. In this prospective study, we want to extend our observation to the cancers originating from lymphoid tissue. Non-Hodgkin lymphoma is a cancer of lymphoid tissue. The main cell type found in lymphoid tissue is the lymphocyte. The 2 main types of lymphocytes are B-lymphocytes (B-cells) and T-lymphocytes (T-cells). B-cell lymphomas are much more common than T-cell lymphomas. In the U. S., 85% of all cases of non-Hodgkin lymphoma come from B lymphocytes (B-cell) and 15% from T lymphocytes (T-cell). We performed immunohistochemistry analysis to investigate the expression pattern of E6-AP in normal lymph nodes and lymphoid tumors. Tissue micro arrays representing samples from 60 different patients were analyzed in this study. Our analysis suggest that on an average there was about 55 % reduction in E6-AP protein levels in B-cell lymphomas (P =0.0001) and 98.5 % reduction in E6-AP levels in T-cell lymphomas (P =0.0002) compared to normal lymph node. Based on our previous studies in breast and prostate tumors and considering our current finding of reduced/loss of E6-AP in lymphoid tumors, we propose that E6-AP may act as a potential tumor suppressor protein. This proposed idea is consistent with our in vivo data generated from E6-AP null mice which shows that the number of B- and T-cells are significantly increased in spleen compared to normal wild-type animals. Taken together our data establish the role of E6-AP as a potential growth and tumor suppressor protein.

scholarly journals Radioimmunotherapy with iodine 131I tositumomab for relapsed or refractory B-cell non-Hodgkin lymphoma: updated results and long-term follow-up of the University of Michigan experience

Blood ◽  
2000 ◽  
Vol 96 (4) ◽  
pp. 1259-1266 ◽  
Author(s):  
Mark S. Kaminski ◽  
Judith Estes ◽  
Kenneth R. Zasadny ◽  
Isaac R. Francis ◽  
Charles W. Ross ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin Lymphoma ◽  
De Novo ◽  
Hematologic Toxicity ◽  
Low Grade ◽  
Cell Transplant ◽  
Non Hodgkin Lymphoma ◽  
Therapeutic Doses ◽  
131I Tositumomab

Abstract CD20-targeted radioimmunotherapy is a promising new treatment for B-cell non-Hodgkin lymphoma (NHL). We now provide updated and long-term data on 59 chemotherapy-relapsed/refractory patients treated with iodine 131I tositumomab in a phase I/II single-center study. Fifty-three patients received individualized therapeutic doses, delivering a specified total-body radiation dose (TBD) based on the clearance rate of a preceding dosimetric dose. Six patients received dosimetric doses only. Dose-escalations of TBD were conducted separately in patients who had or had not undergone a prior autologous stem cell transplant (ASCT) until a nonmyeloablative maximally tolerated TBD was established (non-ASCT = 75 cGy, post-ASCT = 45 cGy). Fourteen additional non-ASCT patients were treated with 75 cGy. Unlabeled antibody was given prior to labeled dosimetric and therapeutic doses to improve biodistribution. Forty-two (71%) of 59 patients responded; 20 (34%) had complete responses (CR). Thirty-five (83%) of 42 with low-grade or transformed NHL responded versus 7 (41%) of 17 with de novo intermediate-grade NHL (P = .005). For all 42 responders, the median progression-free survival was 12 months, 20.3 for those with CR. Seven patients remain in CR 3 to 5.7 years. Sixteen patients were re-treated after progression; 9 responded and 5 had a CR. Reversible hematologic toxicity was dose limiting. Only 10 patients (17%) had human anti-mouse antibodies detected. Long-term, 5 patients developed elevated thyroid-stimulating hormone levels, 5 were diagnosed with myelodysplasia and 3 with solid tumors. A single, well-tolerated treatment with iodine 131I tositumomab can, therefore, produce frequent and durable responses in NHL, especially low-grade or transformed NHL.

scholarly journals GENE-41. UNDERSTANDING THE DIFFERENCES IN ADOLESCENT AND YOUNG ADULT (AYA) GLIOMAS AND OLDER ADULT (OA) GLIOMAS BASED ON FUNCTIONAL MOLECULAR SUBGROUPS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi106-vi106
Author(s):  
Catherine Bi ◽  
Ashwin Subramaniam ◽  
Joanne Xiu ◽  
Amy Heimberger ◽  
Sharon Michelhaugh ◽  
...  
Keyword(s):  
Dna Repair ◽  
Transcriptional Regulation ◽  
Tumor Suppressor ◽  
Metabolic Pathways ◽  
Tumor Suppressor Genes ◽  
Mutation Frequency ◽  
Pik3ca Mutation ◽  
Low Grade ◽  
Suppressor Genes ◽  
Pathway Gene

Abstract BACKGROUND Gliomas in the AYA population (15–39 years of age) have unique biological characteristics and need to be better characterized. METHODS Glioma tumors in AYA subjects and subjects >65 years of age (OA) were analyzed by next generation sequencing using a 592 gene panel. Pathogenic mutations were classified into five functional groups, viz. metabolic pathways genes (IDH1/2, FH), tumor suppressor genes (TP53, RB1, APC, NF1/2, PTEN, TSC1/2), genes involved in DNA repair (MMR genes, BRCA1/2, POLE, ARID1A, CHEK2, ATM, BLM, BRIP1, WRN, BARD1, POT1, MUTYH), oncogenes (BRAF, NRAS, HRAS, EGFR, PDGFRA, FGFR1, NOTCH1, MYCN), and genes involved in transcriptional regulation (SETD2, H3F3A, KMTD2A/2C/2D, KDM6A, PIK3CA). Mutation frequency in AYA tumors and OA tumors were compared using Chi-squared analysis (Pearson’s score χ2; likelihood ratio LR). RESULTS 720 unique gliomas tumors were analyzed: 118 AYA, 602 OA; 420 males, 300 females. When both groups are considered together, glioblastoma was the most common histology (75%), followed by grade 3 astrocytoma (13%), glioma NOS (3.8%), oligodendrogliomas (3%), low grade gliomas (2.9%) and other (2.3%). AYA tumors harbored more metabolic pathway gene mutations (χ2 137.7, p< 0.0001) driven primarily by IDH1 mutations, while OA tumors had a higher mutation frequency in oncogenes (χ2 9.22, p=0.0024) driven by EGFR mutations (LR 27.567) and tumor suppressor genes (χ2 40.35, p< 0.0001) driven by NF1 (LR 18.147) and PTEN (LR 66.216). No significant differences were noted in mutation frequency in DNA repair or transcriptional regulation genes. However, AYA glioblastoma tumors had a significant increase in mutations in genes involved in chromatin remodeling, (χ2 11.43, p=0.0007) even after excluding H3F3A. CONCLUSIONS Functional genomic classification of AYA tumors may help develop better targeted therapies, especially focused on genes involved in metabolic pathways and transcriptional regulation.

Antiviral treatment in Hepatitis C Virus (HCV)- related low grade non-Hodgkin lymphoma: An update of a multicenter study

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17526-17526
Author(s):  
D. Vallisa ◽  
P. Bernuzzi ◽  
A. Lazzaro ◽  
E. Trabacchi ◽  
A. Arcari ◽  
...  
Keyword(s):  
Viral Load ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Antiviral Treatment ◽  
Low Grade ◽  
Viral Genotype ◽  
Non Hodgkin Lymphoma ◽  
Hematological Response ◽  
Genotype 2

17526 Background: HCV is largely diffuse in North-western Europe and U.S.A. It has been shown to play a role both in hepatocellular carcinoma and in B-cell non-Hodgkin lymphoma (B-NHL). Up to now the exact biological mechanisms that could explain the lymphomagenic role of the virus are under study. Methods: We have previously published a series of 13 patients, affected by low grade B-cell NHL and characterized by an indolent course (i.e. doubling time less than 1 year, no bulky disease), who underwent antiviral treatment only with peghilated interferon and ribavirin (peghilated interferon 50–70 microgram weekly, ribavirin 1000–1200 mg daily). Now we report the second update of this study. Up to now 17 patients are evaluable with a mean follow up of 12.1 ± 8 months (range 2–31 months). Results: Eight patients experienced complete or good partial haematological response that has lasted up to now with a mean follow up of 19,5 months, among them 3 splenic marginal lymphomas, 2 nodal marginal, 1 follicular lymphoma, 1 plasmocytoid and 1 marginal extranodal lymphoma. Three other patients achieved a long lasting partial response. The only one relapse (marginal nodal lymphoma) occurred about one year after the end of treatment, hematological relapse happened together with viral relapse, the lymphoma reappeared as highly chemo resistant high grade lymphoma, and two months later the patient died. Interestingly complete and good partial responses were more likely to be seen in viral genotype 2 (p = 0.04) and were strictly related to the decrease of viral load under treatment (p = 0.005). Toxicity causes the stop of the treatment in 3 patients; however one of them was able to achieve complete hematological response. Time to achieve hematological response was quite long (mean 8 ± 4.5 months). Conclusions: This kind of experience strongly provides a role for antiviral treatment in patients affected by HCV related low grade B-cell NHL. Especially viral genotype 2 infection may be considered a good prognostic marker for hematological response as well as decrease of viral load under treatment. Toxicity in our hands was however significant and further experiences are warranted in order to better modulate antiviral therapy doses. No significant financial relationships to disclose.

The Value of Fluorescence In Situ Hybridization and Polymerase Chain Reaction in the Diagnosis of B-Cell Non-Hodgkin Lymphoma by Fine-Needle Aspiration

2004 ◽  
Vol 128 (12) ◽  
pp. 1395-1403 ◽  
Author(s):  
Anne M. Safley ◽  
Patrick J. Buckley ◽  
Andrew J. Creager ◽  
Rajesh C. Dash ◽  
Leslie G. Dodd ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Fine Needle Aspiration ◽  
Cell Lymphoma ◽  
Molecular Genetic ◽  
Needle Aspiration ◽  
Low Grade ◽  
Fine Needle ◽  
Non Hodgkin Lymphoma

Abstract Context.—Molecular genetic analyses have been predicted to improve the diagnostic accuracy of fine-needle aspiration of B-cell non-Hodgkin lymphoma. Objective.—To determine the value of routine molecular genetic assays, polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH), in the diagnosis of B-cell non-Hodgkin lymphoma by fine-needle aspiration (FNA). Design.—A multiparametric method, including cytology, flow cytometry, PCR, and FISH, was prospectively evaluated in the diagnosis of B-cell non-Hodgkin lymphoma by FNA. Aspirates from 30 consecutive patients with suspected hematolymphoid malignancies were collected. All aspirates were triaged through a uniform program including cell-size analysis, B- and T-cell clonality studies, flow cytometric immunophenotyping, and bcl-1 and bcl-2 gene rearrangements by PCR and FISH. After completion of FNA evaluations, FNA results were compared with diagnoses from prior or subsequent surgical biopsies. Results.—Monoclonal B-cell populations were detected in 18 of 20 B-cell non-Hodgkin lymphomas by flow cytometry and PCR. bcl-1 gene rearrangement was detected in 2 of 2 cases of mantle cell lymphoma. bcl-2 rearrangement was detected in 5 cases including 4 of 4 low-grade follicular lymphomas and 1 transformed follicular lymphoma. By incorporating the results of molecular genetic and ancillary diagnostics, a definitive classification was reached in 12 cases of B-cell non-Hodgkin lymphoma by FNA, including all cases of low-grade follicular lymphoma (4/4) and mantle cell lymphoma (2/2) and approximately 50% of small lymphocytic lymphoma (2/4) and large B-cell lymphoma (4/8). Ten of the 12 cases with a final classification reached by FNA had either prior or follow-up surgical biopsies, and all 10 cases showed agreement between the diagnoses rendered on FNA and surgical biopsies. Conclusions.—With proper handling and management of specimens, FNA can routinely provide samples adequate for molecular genetic studies, in addition to cytomorphology and flow cytometry, making it possible to consistently render accurate and definitive diagnoses in a subset of B-cell non-Hodgkin lymphomas. By incorporating FISH and PCR methods, FNA may assume an expanded role for the primary diagnosis of B-cell non-Hodgkin lymphoma.

scholarly journals Randomized comparison of cladribine alone or in combination with cyclophosphamide, and cyclophosphamide, vincristine and prednisone in previously untreated low‐grade B‐cell non‐Hodgkin lymphoma patients

Cancer ◽  
2008 ◽  
Vol 113 (2) ◽  
pp. 367-375 ◽  
Author(s):  
Ewa Kalinka‐Warzocha ◽  
Jaroslaw Wajs ◽  
Ewa Lech‐Maranda ◽  
Bernadetta Ceglarek ◽  
Jerzy Holowiecki ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin Lymphoma ◽  
Low Grade ◽  
Non Hodgkin Lymphoma
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