Monitoring disease in lymphoma and CLL patients using molecular techniques

Gribben, John G.

doi:10.1053/beha.2002.0191

Cited by 12 publications

(9 citation statements)

References 80 publications

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“…4 In addition, the documentation of a monoclonal AR gene rearrangement provides a molecular fingerprint of the neoplasm, which can then be used for subsequent, and prognostically relevant, minimal residual disease assessment. 5,6 It is within this context of the frequent utility of these assays that the article by Tan and colleagues in this issue of The Journal of Molecular Diagnostics 7 is of interest and warrants commentary. One of the take-home messages of their study is that, among T-cell lymphomas, it is not only in the biologically fascinating entity of angioimmunoblastic T-cell lymphoma that one is likely to encounter the apparent contradictory presence of a monoclonal IGH gene rearrangement in about one-third of such cases, but also in a similar proportion of cases of T-cell lymphomas in the "wastebasket" category of peripheral T-cell lymphoma, unspecified.…”

mentioning

confidence: 99%

Immunoglobulin and T-Cell Receptor Gene Rearrangements: Minding Your B's and T's in Assessing Lineage and Clonality in Neoplastic Lymphoproliferative Disorders

Bagg

2006

The Journal of Molecular Diagnostics

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Antigen receptors (ARs), namely immunoglobulins on B cells and T cell receptors on T cells, are one of the central components of the adaptive immune response, providing the ability to recognize antigens in a humoral and cellular context, respectively. One of the major mechanisms underlying the generation of the remarkably diverse immune response, despite the rather limited number of genes encoding ARs, is the process of gene rearrangement. Other mechanisms contributing to this diversity include the deletion and insertion of N-nucleotides by the enzyme terminal deoxynucleotidyl transferase, which occurs early in lymphoid ontogeny in both B and and T cells, essentially in tandem with the rearrangement process, and somatic hypermutation, which is restricted to the later, germinal center phase of B cell development. During the rearrangement of AR (immunoglobulin [IG] and T cell receptor [TCR]) genes, there is an apparent random shuffling and rejoining of the various segments of these genes. These segments are the variable (V), diversity (D), and joining (J) regions; V and J segments are present in all AR genes, with D segments present only in some. While the determination of V, D, or J segments to be used in a specific rearrangement is apparently stochastic, the mechanisms through which the actual rearrangement occur is not, in that specific heptamer and nonamer recombination signal sequences (RSS) flank these segments and that the process is initiated by a specific complex that includes RAG1 and RAG2 (collectively RAG, proteins of the recombination activating genes).

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confidence: 99%

Immunoglobulin and T-Cell Receptor Gene Rearrangements: Minding Your B's and T's in Assessing Lineage and Clonality in Neoplastic Lymphoproliferative Disorders

Bagg

2006

The Journal of Molecular Diagnostics

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“…While it is well known that not all CTCs give rise to clinically significant metastatic deposits, it has been demonstrated that patients with persistent seeding of CTCs are more likely to develop clinical metastases and resistance to treatment. [2][3][4] Lack of a marker specific for urothelial cancer has been the main obstacle in the detection of CTCs in patients with bladder cancer compared to other solid tumors. However, studies have led to the discovery of UPs, the first urothelium-specific marker, and to the cloning of their cDNAs and genes.…”

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confidence: 99%

Detection of circulating cancer cells expressing uroplakins and epidermal growth factor receptor in bladder cancer patients

Osman

Kang

Lee

et al. 2004

Intl Journal of Cancer

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Our purpose was to determine the clinical relevance of the detection of circulating tumor cells (CTCs) expressing urothelial and epithelial markers in bladder cancer patients. Sixty-two patients who presented to Memorial Sloan-Kettering Cancer Center between July 2000 and September 2001 were studied. Peripheral blood was tested by nested RT-PCR assay for uroplakins (UPs) Ia, Ib, II and III as well as for epidermal growth factor receptor (EGFR). We determined the sensitivity and specificity of each individual marker and the combinations of UPIa/UPII and UPIb/UPIII. The latter strategy was based on our data, which showed that UPIa and UPIb form heterodimers with UPII and UPIII, respectively. Forty patients had clinically advanced bladder cancer and 22 had no evidence of disease at the time of assay. Eight of the 22 patients recurred during the follow-up period. All 8 patients were positive at presentation for UPIa/UPII. The combination of UPIa/UPII provided the best sensitivity (75%) of detecting CTCs, with a specificity of 50%. The combination of UPIb/UPIII was the most specific (79%) but had modest sensitivity (31%). Detection of EGFR-positive cells alone and in combination with UPs was inferior to that for UPIa/UPII. Combinations of urothelial markers are superior to single urothelial or epithelial markers in detecting CTCs in bladder cancer patients. Further efforts are under way to confirm the potential predictive value of these markers in a prospectively designed study of a larger cohort of patients.

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“…182,183,218,[263][264][265][266][267][268][269][270] Interpreting and comparing data are impaired by the wide array of techniques employed that generate data of a qualitative or quantitative nature, and by the lack of standardisation of methodology and criteria for interpreting results, particularly those generated by newer RQ-PCR techniques. Progress towards standardisation of methodology has been made by the European laboratories involved in the BIOMED Concerted Action 271,272 and this approach needs to be fostered among laboratories involved in MRD detection.…”

Section: Minimal Residual Disease (Mrd) Detection and Monitoringmentioning

confidence: 99%

“…177,183,270 3. To identify residual clonal cells after therapy and after marrow transplantation 270 and the quantification of the residual disease. 4.…”

Section: Aims Of Mrd Detection and Monitoringmentioning

confidence: 99%