Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the expression of the immunoglobulin-associated membrane protein B29 in 499 cases of chronic B cell diseases using the monoclonal antibody SN8 (CD79b). SN8 was positive in 5% (17/330) of chronic lymphocytic leukemia (CLL) and 100% (15/15) of B prolymphocytic leukemia. The expression of B29 in other B cell disorders was, as a rule, significantly higher than in CLL. Two thirds of non-Hodgkin's lymphomas in leukemic phase were SN8 positive, including lymphoplasmacytic (45%), follicular (83%), mantle cell (92%) and splenic lymphoma with villous lymphocytes (74%) while only 25% of hairy cell leukemias were SN8 positive. Within CLL, 2.3% of typical cases were SN8+ while 16% of cases with atypical morphology and an increased number of prolymphocytes were SN8+. Our results suggest a useful role for SN8 in the immunophenotypic differentiation of B cell disorders as a marker for non-CLL diseases. The analysis of B29 expression may throw light into the structure of the B cell antigen receptor in B cell malignancies while the distinctive reactivity profile of SN8 has direct applications to diagnosis.
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PMID:Expression of the immunoglobulin-associated protein B29 in B cell disorders with the monoclonal antibody SN8 (CD79b). 894 38

The origin of Reed-Sternberg (RS) cells, the neoplastic cells of Hodgkin's disease, has long remained controversial. Dendritic cells (DCs) are highly specialized antigen-presenting cells that have the unique capacity to prime naive T cells, and they may be progenitors of RS cells in a population of Hodgkin's disease cells. In this study, the KM-H2 cell line, previously established from a patient with Hodgkin's disease of mixed cellularity, was reevaluated for its cellular derivation, particularly in terms of DCs. KM-H2 cells were demonstrated to carry the newly proposed DC-associated molecules fascin, CD83, and DEC-205, as well as costimulatory molecules such as CD40, CD80, and CD86. In addition, KM-H2 cells were shown to be able to potently stimulate peripheral blood T cells and to have the strong endocytotic activity of fluorescein isothiocyanate-dextran. On the other hand, KM-H2 cells were shown to have variable-diversity-joining recombination of the immunoglobulin H gene, although they did not express any subclasses of immunoglobulin and they were negative for CD79a and CD79b. In addition, KM-H2 cells produced the messenger RNA of the Pax-5 gene. These findings lead to a hypothesis that KM-H2 cells originated from the cells that had differentiated through the possible common DC-B-cell progenitors along the newly proposed pathway.
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PMID:A Hodgkin's disease cell line, KM-H2, shows biphenotypic features of dendritic cells and B cells. 1137 38

CD79 is composed of CD79a and CD79b components expressed almost exclusively on B cells and B-cell neoplasms. CD79a and CD79b expression precedes immunoglobulin (Ig) heavy-chain gene rearrangement and CD20 expression during B-cell ontogeny and disappears later than CD20 in the late (plasma cell) stage of B-cell differentiation. Therefore, antibodies to CD79a and CD79b are useful in the differential diagnosis of B-cell neoplasms from T-cell neoplasms or myeloid neoplasms, or L and H lymphocyte predominance Hodgkin's lymphoma from classic Hodgkin's lymphoma. In addition, CD79a and CD79b antibodies are useful markers in the diagnosis of precursor B-acute lymphoblastic leukemia (pre-B-ALL) because many of these tumors are negative for other B-cell markers, such as CD20 and CD45RA. Furthermore, for B-cell neoplasms, wherein CD20 expression is aberrantly lost, such as in diffuse large B-cell lymphoma, or for B-cell neoplasms after CD20-antibody therapy, CD79a may be used as a first-line B-cell marker for the diagnosis. In this review, the authors discuss the molecular biology of CD79 and the frequency and usefulness of CD79 expression in these neoplasms.
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PMID:CD79: a review. 1139 39

Six cases of non-Hodgkin B-cell lymphoma that mimicked either chronic lymphocytic leukemia (CLL) or a CLL variant at presentation are reported. The patients ranged from 54 to 89 years and included three females and three males. All six patients had prominent peripheral blood lymphocytosis at presentation; the initial morphologic impression was CLL in three cases, CLL/prolymphocytic leukemia (PLL) in two cases, and PLL in one. Five patients had bone marrow biopsies; each showed a lymphoid infiltrate in a focally random, interstitial, and/or diffuse pattern. Flow cytometric immunophenotyping showed CD20-positive B cells with surface immunoglobulin (Ig) light chain restriction in all six patients. The five cases resembling CLL or CLL/PLL had at least a subset of CD5-positive B cells, whereas CD5 was absent in the one case that resembled PLL. CD23 was positive in three of the four cases studied that resembled CLL or CLL/PLL; CD79b was positive in three, FMC7 was positive in two, and surface Ig and CD20 were brightly positive in three. A t(11;14) (q13;q32) was found in four cases that resembled CLL or CLL/PLL; they were subsequently diagnosed as mantle cell lymphoma. The remaining two cases mimicking CLL or PLL were diagnosed as lymphomas of follicle center origin with leukemic phase based on the presence of t(14;18) (q32;q21). Thus although the morphology of these six cases resembled CLL or variants, and immunophenotyping by flow cytometry showed overlapping features, genetic studies enabled distinction of these leukemic non-Hodgkin lymphoma from chronic lymphocytic leukemia or variants.
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PMID:Leukemic phase of B-cell lymphomas mimicking chronic lymphocytic leukemia and variants at presentation. 1242 88

Multiparametric clinical flow cytometry has evolved from two-parameter quantitative assessment of lymphocytes to assessment of many qualitative parameters of suspensions obtained from bone marrow, peripheral blood, and lymph nodes for hematopathology. Nowadays, lymphoma immunophenotyping is a necessary complement to morphology and molecular parameters in the diagnosis and monitoring of human hematopoietic malignancies. The aim of the present study was to determine whether immunophenotypic differences could be used to distinguish between non-Hodgkin's B cell lymphoma (NHL-B) and the normal B cell subpopulation by assessing the variability in the patterns of expression of some lymphoid antigens (CD5, CD19, FMC7, CD23, CD20, CD79b, CD38, CD22, CD10, sIgkappa, sIglambda, mIgA, mIgG, mIgM, and mIgD) in specimens obtained from patients with NHL-B. We have studied peripheral blood samples, lymph node suspensions, and bone marrow specimens from 20 patients with malignant lymphoma and from controls without oncohematologic disease. Some patients showed stable patterns of antigen expression that remained unchanged over time and were consistent from one specimen to another. Other patients showed more variability in the pattern of antigen expression from different specimens. The two-way cluster analysis of antigens revealed three patterns of expression: (1) most cells in most cases positive (CD5, CD19, CD20, CD23, CD45); (2) most cells in most cases negative (CD10, mIgG, CD22, CD23,CD38); and (3) a mixed pattern with a variable number of positive cases and a variable percentage of positive cells in individual cases (CD22, CD38, CD79b, FMC7, mIgD, mIgM, mIgA, mIgG, sIgkappa, sIglambda). The expression of several antigens was strongly interdependent, even when antigens belonged to entirely different gene families. Such antigen pairs were CD19/CD45; CD19/CD79b; CD23/Igkappa; and CD45/CD79b. Our results suggest that different factors may determine the stability or the variability of such multiantigen expression, particularly the biology and function of the different antigens and the mechanisms of disease dissemination and progression.
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PMID:Flow cytometric immunophenotyping analysis of patterns of antigen expression in non-Hodgkin's B cell lymphoma in samples obtained from different anatomic sites. 1565 Feb 71

Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL) and primary effusion lymphoma (PEL) are derived from germinal center (GC) and post-GC B cells, respectively. Neither express many of the B cell genes or surface markers typically expressed by other GC-derived B cell lymphomas or normal B cells. This loss of B cell gene expression is not due to a lack of essential transcription factors, as studies have shown that the ectopic expression of missing transcription factors failed to reactivate endogenous target genes. These results implicate epigenetic mechanisms extinguishing B cell gene expression. Silenced endogenous B cell genes representing a surface receptor, B29 (Igbeta, CD79b), a signaling molecule, TCL1, and a transcription factor, Bob1 (OCA-B, OBF-1), were reactivated by 5-aza-2'-deoxycytidine, indicating that gene silencing in HRS and PEL cells is due to DNA methylation. Genomic bisulfite sequencing corroborated this prediction and revealed three distinct patterns of methylation for the silenced B29 and TCL1 promoters. These distinct patterns consisted of 5' promoter CpG methylation alone, 5' and 3' promoter CpG methylation sparing sites in the central cores, and complete CpG methylation throughout the promoter regions. The silenced Bob1 promoter showed one pattern of dense CpG methylation at essentially all sites. These consistent patterns predict that, although gene silencing in many HRS and PEL cells mimics appropriate gene silencing, in some cases of complete CpG methylation throughout entire promoters both the activation and targeting of methylation is abnormal.
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PMID:Patterned CpG methylation of silenced B cell gene promoters in classical Hodgkin lymphoma-derived and primary effusion lymphoma cell lines. 1596 59

Targeting cytotoxic drugs to cancer cells using antibody-drug conjugates (ADCs), particularly those with stable linkers between the drug and the antibody, could be an effective cancer treatment with low toxicity. However, for stable-linker ADCs to be effective, they must be internalized and degraded, limiting potential targets to surface antigens that are trafficked to lysosomes. CD79a and CD79b comprise the hetrodimeric signaling component of the B-cell receptor, and are attractive targets for the use of ADCs because they are B-cell-specific, expressed in non-Hodgkin lymphomas (NHL), and are trafficked to a lysosomal-like compartment as part of antigen presentation. We show here that the stable-linker ADCs anti-CD79b-MCC-DM1 and anti-CD79b-MC-MMAF are capable of target-dependent killing of nonHodgkin lymphoma cell lines in vitro. Further, these 2 ADCs are equally effective as low doses in xenograft models of follicular, mantle cell, and Burkitt lymphomas, even though several of these cell lines express relatively low levels of CD79b in vivo. In addition, we demonstrate that anti-CD79b ADCs were more effective than anti-CD79a ADCs and that, as hypothesized, anti-CD79b antibodies downregulated surface B-cell receptor and were trafficked to the lysosomal-like major histocompatibility complex class II-positive compartment MIIC. These results suggest that anti-CD79b-MCC-DM1 and anti-CD79b-MC-MMAF are promising therapeutics for the treatment of NHL.
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PMID:Antibody-drug conjugates targeted to CD79 for the treatment of non-Hodgkin lymphoma. 1737 36

Here we describe the generation of an antibody-drug conjugate (ADC) consisting of a humanized anti-CD79b antibody that is conjugated to monomethylauristatin E (MMAE) through engineered cysteines (THIOMABs) by a protease cleavable linker. By using flow cytometry, we detected the surface expression of CD79b in almost all non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia patients, suggesting that anti-CD79b-vcMMAE could be widely used in these malignancies. By using NHL cell lines to simulate a patient population we discovered that a minimal cell-surface expression level of CD79b was required for in vitro activity. Within the subpopulation of cell lines above this minimal threshold, we found that sensitivity to free MMAE, mutation of cancer genes, and cell doubling time were poorly correlated with in vitro activity; however, the expression level of BCL-XL was correlated with reduced sensitivity to anti-CD79b-vcMMAE. This observation was supported by in vivo data showing that a Bcl-2 family inhibitor, ABT-263, strikingly enhanced the activity of anti-CD79b-vcMMAE. Furthermore, anti-CD79b-vcMMAE was significantly more effective than a standard-of-care regimen, R-CHOP (ie, rituximab with a single intravenous injection of 30 mg/kg cyclophosphamide, 2.475 mg/kg doxorubicin, 0.375 mg/kg vincristine, and oral dosing of 0.15 mg/kg prednisone once a day for 5 days), in 3 xenograft models of NHL. Together, these data suggest that anti-CD79b-vcMMAE could be broadly efficacious for the treatment of NHL.
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PMID:Therapeutic potential of an anti-CD79b antibody-drug conjugate, anti-CD79b-vc-MMAE, for the treatment of non-Hodgkin lymphoma. 1963 98

Morphological differentiation between benign and malignant lymphoproliferative disorders (LPDs) can be challenging. Immunophenotyping (IPT) by either technique, flow cytometry or immunohistochemistry (IHC), is an important step in solving such difficulty. Thirty-five newly diagnosed patients with chronic B-cell neoplasms (11 chronic lymphocytic leukemia, 22 non Hodgkin lymphoma and 2 hairy cell leukemia) were included in this study with age range from 20 to 70 years. Monoclonal antibodies surface expression using lymphoproliferative disorders panel (CD45, CD19, CD5, CD10, CD11c, CD20, CD22, CD23, CD38, CD79b, FMC7, CD103, CD25, kappa and lambda light chains) by flow cytometry was done on bone marrow samples. CD20, CD5, CD23, Bcl-2, Bcl-6, kappa and lambda light chain immunostaining were performed on fixed bone marrow trephine biopsy specimen. The sensitivity of IHC was 81.8% in chronic lymphocytic leukemia (CLL) and 100% in non Hodgkin lymphoma (NHL) as regards CD20, 100% in both groups as regards CD5, 46% in CLL and 66.7% in NHL as regards CD23, 33.3% in CLL and 50% in NHL as regards kappa chain, 20% in CLL and 33.3% in NHL as regards lambda chain. We found that IHC and flow cytometry are equally effective in diagnosing CLL; however, IHC might be slightly more sensitive than flow cytometry in detecting bone marrow infiltration in NHL and hairy cell leukemia (HCL).
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PMID:Immunophenotyping of chronic B-cell neoplasms: flow cytometry versus immunohistochemistry. 2256 17

Recent classifications of non-Hodgkin's lymphomas based on combination of morphologic, immunophenotypic, and cytogenetic criteria have individualized mantle cell lymphoma (MCL). This clinico-biological entity which accounts for 3 to 10% of all non-Hodgkin's lymphomas, now appears to be a biological and therapeutic model for the understanding and treatment of hematologic malignancies. The present study consisting of two cases of MCL collated at laboratory of hematology of Rabat Ibn Sina hospital. The morphological appearance of MCL is characterized by diffuse or nodular lymph infiltration in the mantle zone, the osteo-medullary biopsy shows an interstitial infringement characterized by the presence of lymphocytes resembling centrocytes with cleaved and angular nuclei, dispersed chromatin, inconspicuous nucleoli and scanty cytoplasm. The flow cytometry showed immunophenotype positive for surface Ig, CD19, CD20, CD22, CD79b, CD5 and cyclin D1, and negative for CD10, CD23 and CD25. In conclusion, the methods of diagnosis and prognosis evaluation of mantle cell lymphoma are based on the nodular, medullary and blood morphology, the immunophenotypic, cytogenetic and molecular study of neoplastic cells.
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PMID:[Mantle cell lymphoma diagnosis]. 2339 34


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