Pathology of lymphoma progression

Hk, Müller-Hermelink; Zettl, Andreas; Pfeifer, Walther M.; G, Ott

doi:10.1046/j.1365-2559.2001.01120.x

Cited by 50 publications

(38 citation statements)

References 150 publications

(243 reference statements)

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“…4,7 Therefore, it has been proposed to use the term 'lymphoma progression' denoting cases where DLBL evolved from CLL, in contrast to the term 'composite lymphoma', indicating different clonal origin of CLL and DLBL tumorclones. 6 The present V H gene mutational status analysis demonstrates that the development of DLBL through 'lymphoma progression' occurred only in CLL patents with unmutated V H genes. Unmutated CLLs frequently carry distinct genomic aberrations such as trisomy 12 and 17p and 11q deletions.…”

Section: Discussionmentioning

confidence: 71%

“…It has been demonstrated that DLBL may occur in two distinct pathways in CLL patients: CLL and DLBL can be either clonally related or represent clonally unrelated neoplasms; however, the high-risk variants of CLL that are prone to develop Richter's syndrome have not been determined. 6,7 The V H gene sequences of CLL and DLBL samples have been analyzed in only four cases of Richter's syndrome: in a previous report, we found stable, unmutated V H sequences in a clonal progression of CLL to DLBL, 7 but Cherepakihin et al 8 demonstrated ongoing hypermutation in an another case, similar to transformation of follicular lymphoma to DLBL. 9,10 Nakamura et al 11 reported two cases of Richter's syndrome, where DLBL tumorclones expressed mutated V H genes, but these tumorclones were unrelated to the original CLLs.…”

Section: Introductionmentioning

confidence: 94%

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Relationship between the mutational status of VH genes and pathogenesis of diffuse large B-cell lymphoma in Richter's syndrome

et al. 2003

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Patients with chronic lymphocytic leukemia (CLL) may develop diffuse large B-cell lymphoma (DLBL), also known as Richter's syndrome. Mutational status of immunoglobulin (Ig) heavychain variable region (V H ) genes have prognostic impact in CLL. Patients with mutated V H genes have a stable disease, whereas patients with unmutated V H gene have more aggressive disease. The mutational status of CLLs that transform to DLBL is unknown. To reveal whether Richter's syndrome occurs in CLLs with mutated or unmutated V H genes, we have performed mutational analysis on serial specimens from eight patients. CLL and DLBL tumorclones were identical in five cases and they were different in three cases. Six CLLs expressed unmutated and two cases expressed mutated V H genes. In five of the six unmutated CLLs, the DLBL clones evolved from CLL tumorclones and the V H genes expressed by DLBLs were also unmutated. In one unmutated and two mutated CLLs, the DLBLs expressed mutated V H genes, but in these three cases the DLBL tumorclones developed as independent secondary neoplasm. These results suggest that Richter's syndrome may develop in both mutated or unmutated CLLs, but clonal transformation of CLL to DLBL occur only in the unmutated subgroup of CLL.

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Section: Discussionmentioning

confidence: 71%

Section: Introductionmentioning

confidence: 94%

Relationship between the mutational status of VH genes and pathogenesis of diffuse large B-cell lymphoma in Richter's syndrome

et al. 2003

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“…Earlier studies on lymphoma have shown that disease progression could either be clonally related or represent clonally unrelated neoplasms (37,38). Clonally unrelated relapses are uncommon but have been reported (37,38).…”

Section: Discussionmentioning

confidence: 99%

“…Clonally unrelated relapses are uncommon but have been reported (37,38). Treatment may induce changes that are responsible for the formation of new neoplasms in patients.…”

Section: Discussionmentioning

confidence: 99%

Chromosomal Imbalances in Diffuse Large B-Cell Lymphoma Detected by Comparative Genomic Hybridization

et al. 2002

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Non-Hodgkin lymphomas (NHL) constitute a heterogeneous group of lymphoid neoplasms that display different morphological, immunological, cytogenetic, and molecular genetic features. The revised European-American classification of lymphoma (1) takes all these features into consideration for the distinction of different lymphoma entities. Lymphomas have been associated with a wide range of recurrent chromosomal abnormalities. Some of these can occur as a single cytogenetic alteration and may sometimes be recurrent in a lymphoma entity, such as the t(14;18)(q32;q21), which is found in 85 to 90% of follicular lymphomas. The occurrence of distinct chromosomal changes in specific histopathological subtypes of NHL has improved the understanding of the genetic basis of lymphomagenesis (2). Diffuse large B-cell lymphomas (DLBCL) constitute approximately 40% of all lymphomas and are typically characterized by an aggressive behavior in

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“…Involvement of the blood (25%) and gastrointestinal tract is also common [23], while infiltration of the central nervous system is rarely detected and may be related to blastoid transformation [24]. Lack of lymph node involvement with isolated massive splenomegaly occurs in some patients, but this is infrequent [21].MCLs may progress to a blastoid variant, as reviewed by Matolcsy [25] and Muller-Hermelink et al [26], but this variant may also arise de novo [24]. The more aggressive blastoid variant is associated with decreased survival [27,28] and 26 70% of MCL patients have a morphological progression towards this variant, detected either during life or at autopsy [29,30].…”

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confidence: 99%

Parallel Gene Expression Profiling of Mantle Cell Lymphoma – How Do We Transform ´Omics Data into Clinical Practice

Ek¹,

Borrebaeck

2007

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DNA microarray technology has been a valuable tool to provide a global view of the changes in gene expression that characterize different types of B cell lymphomas, both in relation to clinical parameters but also in comparison with the non-malignant counterparts. The number of transcripts that can be analyzed on an array has dramatically increased, and now most commercially available arrays cover the whole genome, enabling overall analysis of the transcriptome. The backside of collecting this massive amount of information is that even after strict data filtering, it is impossible to do follow-up studies on all findings. Down-stream analysis is time-consuming and when performing confirmatory experiments on the protein level, the experiments are in most cases restricted to proteins recognized by commercially available reagents. Furthermore, since gene expression data is a comparative method not only are the experimental set-up but also the characteristics of both the sample and reference crucial for our ability to answer the questions posed. Thus, initial care must be taken in the design of the experiment and the preparation of the samples.The aim of this review is to discuss the progress in mantle cell lymphoma research enabled by gene expression analysis and to pinpoint the difficulties in making efficient use of the generated data to provide a fast and accurate clinical diagnosis, efficient stratification of patients into disease sub-groups and improved therapy. MANTLE CELL LYMPHOMA -HISTORICAL PER-SPECTIVESB cell lymphomas are the malignant counterparts of different developmental stages of normal B lymphocytes and are divided into precursor B cell neoplasms and mature/ peripheral B cell neoplasms, according to the WHO classification [1]. B cell differentiation is strictly regulated by homeostatic controls but even so, malignant transformation occasionally proceeds unimpeded [2]. The main groups of B cell neoplasms are precursor B-lymphoblastic leukaemia/lymphoma, Chronic lymphocytic leukaemia/lymphoma (CLL), plasma cell myeloma, extranodal marginal zone (MZ) B cell lymphoma of mucosa-associated lymphoid tissue (MALT) type, follicular lymphoma (FL), mantle cell lymphoma (MCL), diffuse large B cell lymphoma (DLBCL) and Burkitt lymphoma [1].MCL was originally considered to be derived from naïve B cells and most tumors show unmutated variable heavy chain (V H) genes. However, several studies have shown that 10 20% of MCLs have somatically mutated immunoglobulin (Ig) genes, indicating that a sub-group has passed through a differentiation stage involving somatic hypermutation of V H genes [3][4][5][6][7][8]. Recently, it has been shown that using an alternative method up to 60% of the MCL were shown to have <98% homology with the germline sequence and were thus considered to carry somatically mutated Ig genes [9]. In the same study it was further shown that patients with somatically hypermutated V H genes had a better survival *Address correspondence to this author at the Department of Immunotechnology, ...

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Pathology of lymphoma progression

Cited by 50 publications

References 150 publications

Relationship between the mutational status of VH genes and pathogenesis of diffuse large B-cell lymphoma in Richter's syndrome

Relationship between the mutational status of VH genes and pathogenesis of diffuse large B-cell lymphoma in Richter's syndrome

Chromosomal Imbalances in Diffuse Large B-Cell Lymphoma Detected by Comparative Genomic Hybridization

Parallel Gene Expression Profiling of Mantle Cell Lymphoma – How Do We Transform ´Omics Data into Clinical Practice

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