scholarly journals CyclinD1/CyclinD3 Ratio by Real-Time PCR Improves Specificity for the Diagnosis of Mantle Cell Lymphoma

2004 ◽  
Vol 6 (2) ◽  
pp. 84-89 ◽  
Author(s):  
Carol D. Jones ◽  
Katherine H. Darnell ◽  
Roger A. Warnke ◽  
James L. Zehnder
Keyword(s):  
Mantle Cell Lymphoma ◽  
Real Time ◽  
Real Time Pcr ◽  
Cell Lymphoma ◽  
Mantle Cell

Identification of Candidate Tumor Suppressor Genes Silenced Epigenetically in Mantle Cell Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3001-3001
Author(s):  
Norihiko Kawamata ◽  
Takayuki Saitoh ◽  
Sakura Sakajiri ◽  
Phillip H. Koeffler
Keyword(s):  
Tumor Suppressor ◽  
Mantle Cell Lymphoma ◽  
Real Time ◽  
Real Time Pcr ◽  
Tumor Suppressor Genes ◽  
Cell Lymphoma ◽  
Suppressor Genes ◽  
Expression Levels ◽  
Candidate Tumor Suppressor ◽  
Mantle Cell

Abstract Many tumor suppressor genes are silenced by epigenetic mechanisms in human cancers, including mantle cell lymphoma (MCL). In this study, we have used a variety of research tools to screen for genes that are epigenetically silenced in MCL. Changes in the global gene expression profile of the MCL cell line, Jeko1, were analyzed after treatment with the combination of the demethylating agent, 5-aza-2′-deoxycytidine, and the histone deacetylase inhibitor, suberoyl anilide bishydroxamide, by DNA microarray technique. By screening over 22,000 genes, we identified 26 candidate tumor suppressor genes, expression of which were enhanced by the treatment, in the MCL line. Basal expression of these 26 genes were low in Jeko1 cells. The treatment enhanced the expression more than 2 folds and the enhancement was also confirmed by real-time PCR. Methylation status of these 26 genes were examined by bisulfite sequencing and/or combined bisulfite and restriction enzyme digestion assay in Jeko1 cells. We found hypermethylation of a CpG island in the middle of the INPP5F gene. We also found the hypermethylation of that region of INPP5F in normal peripheral blood. We also examined expression levels of these 26 genes in normal mantle cells by real-time PCR and found only 11 genes showed high levels of transcription in laser-dissected normal mantle cells. We examined expression of these 11 genes in eight MCL clinical samples by real-time PCR and found that only three genes, INPP5F, DUSP10 and FGD2 showed very low expression levels. We conclude that expression of INPP5F, DUSP10 and FGD2 genes were suppressed in MCL cells although the expression of these genes are high in normal mantle cells. INPP5F is a inositol phosphatase and could be involved in PI3K pathway. DUSP10 is a dual specific phosphatase and could be involved in JNK pathway. FGD2 is a RAS-GAP gene and could be involved in RAS pathway. These three genes may be candidate tumor suppressor genes in MCL and further functional analysis is ongoing.

Cyclin D1 (CCND1) messenger RNA expression as assessed by real-time PCR contributes to diagnosis and follow-up control in patients with mantle cell lymphoma

2013 ◽  
Vol 41 (12) ◽  
pp. 1028-1037 ◽  
Author(s):  
Ulrike Bacher ◽  
Wolfgang Kern ◽  
Claudia Haferlach ◽  
Tamara Alpermann ◽  
Torsten Haferlach ◽  
...  
Keyword(s):  
Cyclin D1 ◽  
Mantle Cell Lymphoma ◽  
Real Time ◽  
Real Time Pcr ◽  
Messenger Rna ◽  
Cell Lymphoma ◽  
Rna Expression ◽  
Mantle Cell

Real-time Quantitative RT-PCR of Cyclin D1 mRNA in Mantle Cell Lymphoma: Comparison with FISH and Immunohistochemistry

2003 ◽  
Vol 44 (8) ◽  
pp. 1385-1394 ◽  
Author(s):  
Pei Hui* ◽  
John G. Howe* ◽  
Jill Crouch ◽  
Manjunath Nimmakayalu ◽  
Mazin B. Qumsiyeh ◽  
...  
Keyword(s):  
Cyclin D1 ◽  
Mantle Cell Lymphoma ◽  
Real Time ◽  
Cell Lymphoma ◽  
Rt Pcr ◽  
Mantle Cell

Molecular Monitoring of Residual Disease in Patients with Mantle Cell Lymphoma and CLL after Allogeneic Bone Marrow Transplantation Post Reduced Intensity Conditioning.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5398-5398
Author(s):  
Frank Schüler ◽  
Carsten Hirt ◽  
Thomas Kiefer ◽  
Gottfried Dolken
Keyword(s):  
Real Time ◽  
Real Time Pcr ◽  
Acute Gvhd ◽  
Cell Lymphoma ◽  
Therapeutic Interventions ◽  
Clinical Relapse ◽  
Quantitative Real Time Pcr ◽  
Molecular Monitoring ◽  
Lymphoma Cells ◽  
Mantle Cell

Abstract To control circulating lymphoma cells after allogeneic transplantation in order to induce or manipulate graft-versus-lymphoma (GvL) reactivity in case of relapse, molecular monitoring of circulating lymphoma cells was carried out by quantitative real-time PCR for clone-specific IgH(CDR3) sequences on six patients (CLL n=3; mantle cell lymphoma (MCL) n=2; variant hairy cell leukaemia (vHCL) n=1). All patients were considered as high risk for recurrence or relapse because of age, refractory disease, failure after autografting or poor performance status. They had at least one or more high-risk features that precluded the application of a standard myeloablative conditioning regimen. Therefore, they were treated with allogeneic blood stem cell transplantation (BSCT) from unrelated donors after toxicity-reduced conditioning with treosulfan and fludarabine. Molecular relapse was defined as an increase of circulating lymphoma cells by more than three orders of magnitude in the absence of symptoms or signs of clinical relapse. In the three patients with CLL and one MCL patient leukemic cells disappeared from peripheral blood and bone marrow within the first six months after transplant as demonstrated by quantitative PCR. Only short periods of acute GvHD were observed and successfully treated. In 2/6 patients (one with vHCL and one with MCL) a molecular relapse was detected one month (MCL) and 6 months (vHCL) after transplant. A 3-log increase of circulating lymphoma cells was observed within about 20 days (MCL) and 3 months (vHCL) starting from <1 lymphoma cell/500,000 cells to about 1,000 lymphoma cells/100,000 cells. Rapid reduction and withdrawal of immunosuppressive therapy combined with the infusion of the monoclonal antibody rituximab led to the disappearance of circulating lymphoma cells in both patients. It has to be emphasized that in both patients with documented molecular relapse rituximab alone or in combination with chemotherapy has not led to a stable CR or molecular remission before allogeneic BSCT. The disappearance of recurrent lymphoma cells in both patients correlated well with the development of acute GvHD. This fact demonstrates the curing potency of GvL. Serial molecular monitoring at short-term intervals provided the additional important information that further therapeutic interventions, c.f. infusion of donor lymphocytes, were not necessary. All patients monitored are still in continuous complete clinical and molecular remission for almost three years. Clinical relapse of malignant B cell lymphoma after allogeneic BSCT can be successfully treated by immune therapeutic intervention, e.g. reduction and rapid withdrawal of immunosuppression and infusions of peripheral blood lymphocytes from the original blood stem cell donor by establishing graft versus lymphoma (GvL) reactions. In addition, B-cell specific monoclonal antibodies seem to be very helpful for treating relapses. These therapeutic interventions may be even more effective when introduced before clinical relapse, possibly already at molecular relapse detected by quantitative real time PCR. Therefore, molecular monitoring by quantitative real-time PCR carried out at ≤ 3 months intervals may further improve transplant results and the long-term outcome of patients treated within clinical studies.

scholarly journals Real-Time Quantitative Reverse Transcription-PCR for Cyclin D1 mRNA in Blood, Marrow, and Tissue Specimens for Diagnosis of Mantle Cell Lymphoma

2004 ◽  
Vol 50 (1) ◽  
pp. 80-87 ◽  
Author(s):  
John Greg Howe ◽  
Jill Crouch ◽  
Dennis Cooper ◽  
Brian R Smith
Keyword(s):  
Cyclin D1 ◽  
Mantle Cell Lymphoma ◽  
Real Time ◽  
Reverse Transcription ◽  
Cell Lymphoma ◽  
Rt Pcr ◽  
Lymphoproliferative Diseases ◽  
Β2 Microglobulin ◽  
Reverse Transcription Pcr ◽  
Mantle Cell

Abstract Background: Overexpression of cyclin D1 mRNA, found in mantle cell lymphoma (MCL), is a critical diagnostic marker. We investigated the use of real-time reverse transcription-PCR (RT-PCR) for cyclin D1. Methods: We studied 97 fresh specimens (50 blood, 30 bone marrow, 15 lymph node, and 2 other samples) from patients diagnosed with a variety of lymphoproliferative diseases, including 25 cases of MCL. We used real-time quantitative RT-PCR to evaluate cyclin D1 mRNA expression. Because blood and marrow specimens may contain only a minority of potentially malignant cells (as opposed to most lymph nodes) and to increase sensitivity, we normalized the cyclin D1 mRNA concentrations to mRNA of a B-cell-specific marker, CD19, as well as to previously characterized β2-microglobulin mRNA. Results: In 16 of 21 cases of MCL with overt disease, the ratio of cyclin D1 mRNA to β2-microglobulin mRNA was increased, but all 21 cases showed increased ratios of cyclin D1 mRNA to CD19 mRNA. Cyclin D1 mRNA was low or undetectable in various lymphoproliferative diseases, including cases of ambiguous immunophenotype. The mRNA ratios were stable over 3–7 days of sample storage. Conclusion: Quantitative RT-PCR for cyclin D1 mRNA normalized to CD19 mRNA can be used in the diagnosis of MCL in blood, marrow, and tissue.

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