Molecular markers of B-cell lymphoma (original) (raw)

New approaches to lymphoma diagnosis

Hematology

Recent years have brought an explosion of new diagnostic tools to the pathology of lymphomas, which have permitted more precise disease definition and recognition of factors that can predict prognosis and response to treatment. These new methods exploit both the biological features of normal lymphocytes as they progress through differentiation pathways and the genetic abnormalities that characterize malignant transformation. These features can be assessed in individual tumors with techniques that detect proteins (immunophenotyping), messenger RNA (in-situ hybridization), or changes in DNA [Southern blot, PCR, fluorescence in-situ hybridization (FISH), and gene sequencing]. Recently, the novel technology of "gene chips" or DNA microarrays has greatly enhanced the efficiency of analyzing expression of many genes simultaneously at the RNA level. Understanding the relationship of lymphoid neoplasms to their normal counterparts and the genetic events that lead to malignant transformation in lymphoid cells are essential for physicians caring for patients with lymphoma, since these are the basis of modern classification, diagnosis, and prognosis prediction. Although microarray technology is not ready for prime time in the daily diagnosis of lymphoma, practitioners should understand its potential and limitations. The vast majority of lymphoid neoplasms worldwide are derived from B lymphocytes at various stages of differentiation. The review by Harald Stein and colleagues present the events of normal B-cell differentiation that are relevant to understanding the biology of B-cell neoplasia. These include antigen receptor [immunoglobulin (Ig)] gene rearrangement, somatic mutations of the Ig variable region genes, receptor editing, Ig heavy chain class switch, and differential expression of a variety of adhesion molecules and receptor proteins as the cell progresses from a precursor B cell to a mature plasma cell. Most lymphoid neoplasms have genetic abnormalities, many of which appear to occur during the gene rearrangements and mutations that characterize normal B-cell differentiation. Dr. Riccardo Dalla Favera reviews the mechanisms of these translocations and other abnormalities, and their consequences for lymphocyte biology. The association of specific abnormalities with individual lymphomas is reviewed. Dr. Wing C. Chan reviews the technology and applications of DNA microarray analysis, its promises and pitfalls, and what it has already told us about the biology of lymphomas. Finally, what does this all mean? The applications, both current and future, of these discoveries to the diagnosis and treatment of patients with lymphoma are discussed by Dr.

Hematopathology Approaches to Diagnosis and Prognosis of Indolent B-Cell Lymphomas

Hematology, 2005

The advent of new technologies has contributed to improvements in the diagnosis and classification of the non-Hodgkin lymphomas (NHL). Use of a more extensive test menu of paraffin active monoclonal antibodies for immunohistochemistry, molecular cytogenetic studies including standard cytogenetics, multi-color fluorescence in-situ hybridization (FISH), polymerase chain reaction and locus-specific FISH, as well as developments in high-resolution techniques including microarray gene expression profiling and array comparative genomic hybridization (CGH) allow more accurate diagnosis and precise definition of biomarkers of value in risk stratification. The identification of disease-specific gene lists resulting from expression profiling provides a number of potential protein targets that can be validated using immunohistochemistry. We will highlight how improvements in our understanding of lymphoma biology rapidly facilitate the development of new diagnostic reagents that could be used t...

Non-Hodgkin's Lymphoma: Molecular Features of B Cell Lymphoma

Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program, 2000

The rapid increase in the incidence of the B cell non-Hodgkin's lymphomas (NHL) and improved understanding of the mechanisms involved in their development renders timely a review of the theoretical and practical aspects of molecular abnormalities in B cell NHL. In Section I, Dr. Macintyre addresses the practical aspects of the use of molecular techniques for the diagnosis and therapeutic management of patients with B cell NHL. While detection of clonal Ig rearrangements is widely used to distinguish reactive from malignant lymphoproliferative disorders, molecular informativity is variable. The relative roles of cytogenetic, molecular and immunological techniques in the detection of genetic abnormalities and their protein products varies with the clinical situation. Consequently, the role of molecular analysis relative to morphological classification is evolving. Integrated diagnostic services are best equipped to cope with these changes. Recent evidence that large scale gene exp...

Histological and immunohistological analysis of human lymphomas

Critical Reviews in Oncology/Hematology, 1989

staining cell suspensions), '9 can be explained by the recent observation 2°.2t that, in the earliest stages of B cell differentiation, CD22 is intracytoplasmic and only subsequently it emerges onto the surface membrane. We have recently demonstrated a clearcut positivity for the CD3 Ag in the Golgi area of Hodgkin's and Reed-Sternberg cells in cytospins from lymph nodes involved by Hodgkin's disease 22 (see Figure 3), a finding never made in cell suspension studies. Immunohistological techniques can be applied to routinely fixed paraffin-embedded samples, frozen sections from fresh tissue biopsies, or cytological preparations (imprints, smears, and cytospins). Specificity DAKO-LC (29)" Ros-220C (Dr. Faliniy DAKO-4KB5 (30) Clonab MB2 (31) Ki-B3 (32) L26 (28,33) Clonab LN1 (26,27) Clonab LN2 (26,27) HD66 DAKO-UCHLI (34) Clonab MT1 (31) Polyclonal anti-CD3" (Dr.

Expression of B-cell-specific markers in different burkitt lymphoma subgroups

International Journal of Cancer, 1987

Forty-three Burkitt lymphoma (BL) lines were examined for the expression of 5 monoclonal antibody (MAb)-identified B-cell-specific markers and immunoglobulin production. All (13) EBV-negative BL lines were CALLA+LB-I -, whereas 30 EBV-carrying lines showed a more heterogeneous pattern. In the EBV-negative lines, the follicle mantle zone markers BA-I and 35. I C5 were expressed concordantly, at a different level in each line. This coordination was disrupted in EBV-carrying lines. In the EBV-negative lines, there was also an inverted correlation between the expression of 35. I C5 and the germinal center marker BLA, suggesting that some etiologically important event, perhaps the translocation, had fixed the cells at different stages of their transition from one zone to the other. This inverted relationship was also disrupted in the EBV-carrying lines, suggesting that EBV can interfere with the maturation program of the BL cell. This conclusion was also supported by a comparison between 5 EBV-negative BL lines and their EBV-converted sublines. All converted lines have undergone marker changes, but the degree and nature of these changes was different for each EBV-BL line. Both the coordinated expression of BA-l and 35.1C5 and the inverted relationship between CALLA and LB-l were disrupted in several other convertants. We have reexamined our previous finding that the majority of the variant translocation-carrying BL lines were CALLA-LB-

Bone marrow origin of a B-cell lymphoma

To search for precursors of the neoplastic B cells in a patient with a nodular lymphoma. we produced a monoclonal antibody to a variable region idiotope on the lymphoma 1gM heavy chain. Clonal ancestors of the lymphoma cells were identified by this marker among bone marrow pro-B cells (5% to 26%). A second antiidiotype (anti-Id) antibody specific for the complete lymphoma lgMx recognized 1 0% of B cells in bone marrow and blood and >95% of B cells in lymphomatous lymph nodes. including one obtained after tumor conversion to a diffuse large cell lymphoma. Immunoglobulin gene analysis surprisingly

The role of molecular studies in lymphoma diagnosis

Pathology, 2004

Lymphoma classification is based on a multiparametric approach to diagnosis, in which clinical features, morphology, immunophenotype, karyotype and molecular characteristics are important to varying degrees. While in most cases, a diagnosis can be confidently established on the basis of morphology and immunophenotype alone, a small proportion of diagnostically difficult cases will rely on molecular studies to enable a definitive diagnosis. This review discusses the various molecular techniques available including Southern blotting (SB), polymerase chain reaction (PCR), fluorescence in situ hybridisation (FISH)-including multicolour-FISH/spectral karyotyping and comparative genomic hybridisation-and also gene expression profiling using cDNA microarray technology. Emphasis is given to the analysis of antigen receptor gene rearrangements and chromosomal translocations as they relate to lymphoma diagnosis and also in the setting of minimal residual disease (MRD) detection and monitoring. Laboratories performing these tests need to have expertise in these areas of testing, and there is a need for greater standardisation of molecular tests. It is important to know the sensitivity and specificity of each test as well as its limitations and the pitfalls in the interpretation of results. Above all, results of molecular testing should never be considered in isolation, and must always be interpreted in the context of clinical and other laboratory data.