scholarly journals Indications for peripheral light-chain revision and somatic hypermutation without a functional B-cell receptor in precursors of a composite diffuse large B-cell and Hodgkin's lymphoma

2003 ◽  
Vol 84 (2) ◽  
pp. 253-262 ◽  
Author(s):  
Richard Rosenquist ◽  
Fabio Menestrina ◽  
Maurizio Lestani ◽  
Ralf Küppers ◽  
Martin-Leo Hansmann ◽  
...  
Keyword(s):  
B Cell ◽  
Light Chain ◽  
Hodgkin’S Lymphoma ◽  
Somatic Hypermutation ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Hodgkin's Lymphoma ◽  
Large B Cell

Antibody-Drug Conjugates Targeted to CD79 for the Treatment of Non-Hodgkin’s Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2524-2524
Author(s):  
Andrew G. Polson ◽  
Shang-Fan Yu ◽  
Kristi Elkins ◽  
Bing Zheng ◽  
Suzanna Clark ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Cell Receptor ◽  
Burkitt’S Lymphoma ◽  
B Cell Receptor ◽  
Burkitt's Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Antibody Drug

Abstract Non-Hodgkin’s lymphoma (NHL) is an attractive indication for the use of antibody-drug conjugate (ADC) therapeutics since NHL is responsive to conventional chemotherapeutic and antibody treatments. Additionally, experience with rituximab indicates that depletion of normal B-cells can be tolerated without untoward side effects, suggesting that B-cell specific surface proteins that are also prevalent in NHL are potential ADC targets. ADCs with stable linkers have lower toxicity than ADCs containing the same drugs with less stable linkers, however, for these ADCs to be effective the antibody must be degraded to release the active drug. This limits potential targets to surface antigens that upon antibody binding are highly internalized and subsequently degraded. We hypothesized that components of the B-cell receptor (BCR) would be excellent targets for stable-linker ADCs since, when cross-linked, the BCR is targeted to the lysosomal-like compartment MIIC as part of B-cell antigen presentation. In particular, CD79, the signaling component of the B-cell receptor, comprised of two peptide chains CD79a (Igα, mb-1) and CD79b (Igβ, B29), seemed a promising target for ADC treatment of NHL. CD79’s expression is restricted to the B-cell lineage and is on the surface of almost all NHLs. Unlike surface-Ig targeted therapies, which require a new drug for each cancer clone, CD79 sequences are invariant and a single drug is appropriate for the entire population. We found that ADCs targeted to CD79b were more effective than those targeted to CD79a. Furthermore, excellent efficacy is demonstrated with ADCs containing stable linkers and our data indicate in particular, that both anti-CD79b-MCC-DM1 and anti-CD79b-MC-MMAF are effective at low doses in subcutaneous cell-line xenograft models of follicular lymphoma, mantle cell lymphoma, Burkitt’s lymphoma and disseminated Burkitt’s lymphoma. Mechanism-of-action experiments show that anti-CD79b antibodies down regulate surface BCR expression and internalized antibody accumulates in the lysosomal-like MIIC compartment as hypothesized. We evaluated a number of ADCs targeted to other B-cell antigens and found that they were not effective if the ADC had a stable linker, indicating that CD79 has special properties as a target for ADCs. Our results suggest that anti-CD79b-MCC-DM1 and anti-CD79b-MC-MMAF are particularly promising therapeutics for the treatment of NHL.

scholarly journals Prognostic significance of bcl-2 protein expression in aggressive non- Hodgkin's lymphoma. Groupe d'Etude des Lymphomes de l'Adulte (GELA)

Blood ◽  
1996 ◽  
Vol 87 (1) ◽  
pp. 265-272 ◽  
Author(s):  
O Hermine ◽  
C Haioun ◽  
E Lepage ◽  
MF d'Agay ◽  
J Briere ◽  
...  
Keyword(s):  
Overall Survival ◽  
Protein Expression ◽  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Prognostic Significance ◽  
Hodgkin's Lymphoma ◽  
Independent Effect ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Large B Cell

Abstract Little is known about the expression of bcl-2 protein in intermediate and high grade non-Hodgkin's lymphoma (NHL) and its clinical and prognostic significance. We performed immunohistochemical analysis of bcl-2 expression in tumoral tissue sections of 348 patients with high or intermediate grade NHL. These patients were uniformly treated with adriamycin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) in the induction phase of the LNH87 protocol. Fifty eight cases were excluded due to inadequate staining. Of the 290 remaining patients, 131 (45%) disclosed homogeneous positivity (high bcl-2 expression) in virtually all tumor cells, whereas 65 (23%) were negative and 94 (32%) exhibited intermediate staining. High bcl-2 expression was more frequent in B-cell NHL (109 of 214, 51%) than in T- cell NHL (6 of 35, 17%) (P = .0004), and was heterogeneously distributed among the different histological subtypes. Further analysis was performed on the 151 patients with diffuse large B-cell lymphoma (centroblastic and immunoblastic) to assess the clinical significance and potential prognostic value of bcl-2 expression in the most frequent and homogeneous immunohistological subgroup. High bcl-2 expression, found in 44% of these patients (67 of 151), was more frequently associated with III-IV stage disease (P = .002). Reduced disease-free survival (DFS) (P < .01) and overall survival (P < .05) were demonstrated in the patients with high bcl-2 expression. Indeed, the 3-year estimates of DFS and overall survival were 60% and 61%, respectively (high bcl-2 expression) versus 82% and 78%, respectively (negative/intermediate bcl-2 expression). A multivariate regression analysis confirmed the independent effect of bcl-2 protein expression on DFS. Thus bcl-2 protein expression, as demonstrated in routinely paraffin-embedded tissue, appears to be predictive of poor DFS, in agreement with the role of bcl-2 in chemotherapy-induced apoptosis. It might be considered as a new independent biologic prognostic parameter, which, especially in diffuse large B-cell NHL, could aid in the identification of patient risk groups.

scholarly journals CXCR4 upregulation is an indicator of sensitivity to B-cell receptor/PI3K blockade and a potential resistance mechanism in B-cell receptor-dependent diffuse large B-cell lymphomas

Haematologica ◽  
2019 ◽  
Vol 105 (5) ◽  
pp. 1361-1368 ◽  
Author(s):  
Linfeng Chen ◽  
Jing Ouyang ◽  
Kirsty Wienand ◽  
Kamil Bojarczuk ◽  
Yansheng Hao ◽  
...  
Keyword(s):  
B Cell ◽  
Resistance Mechanism ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
B Cell Lymphomas ◽  
Large B Cell

Targeting B-cell receptor and PI3K signaling in diffuse large B-cell lymphoma

Blood ◽  
2021 ◽  
Author(s):  
Wendan Xu ◽  
Philipp Berning ◽  
Georg Lenz
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Cell Receptor ◽  
Genetic Alterations ◽  
B Cell Receptor ◽  
Special Focus ◽  
Large B Cell Lymphoma ◽  
Bcr Signaling ◽  
Large B Cell

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous diagnostic category comprising distinct molecular subtypes characterized by diverse genetic aberrations that dictate patient outcome. As roughly one-third of DLBCL patients are not cured by current standard chemo-immunotherapy a better understanding of the molecular pathogenesis is warranted to improve outcome. B-cell receptor (BCR) signaling is crucial for the development, growth and survival of both normal and a substantial fraction of malignant B-cells. Various analyses revealed genetic alterations of central components of the BCR or its downstream signaling effectors in some subtypes of DLBCL. Thus, BCR signaling and the downstream NF-κB and PI3K cascades have been proposed as potential targets for the treatment of DLBCL patients. As one of the main effectors of BCR activation, PI3K mediated signals play a crucial role in the pathogenesis and survival of DLBCL. In this review, we summarize our current understanding of BCR signaling with a special focus on the PI3K pathway in DLBCL and how to utilize this knowledge therapeutically.

scholarly journals Case of extranodal non-hodgkins lymphoma involving the endometrium and the ovaries: a rare case report

2017 ◽  
Vol 6 (9) ◽  
pp. 4131 ◽  
Author(s):  
Lakshmi Manjeera Malempati ◽  
Neetha Nandan ◽  
Sagarika Babu
Keyword(s):  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Female Genital Tract ◽  
B Cell Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Western World ◽  
Non Hodgkin’S Lymphoma ◽  
Uterine Neoplasm ◽  
Non Hodgkin's Lymphoma ◽  
Large B Cell

Non-Hodgkin’s lymphoma(NHL) is most commonly encountered during childhood and rarely among the adults. Primary malignant lymphoma in the female genital tract are rare Moreover they present with non-specific symptoms and hence there may be delay in the diagnosis. It is difficult to distinguish this condition from the more common uterine neoplasm such as uterine fibroids or sarcoma. Diffuse large B-cell lymphoma (DLBCL) is most commonly seen among the cases of NHL, contributing to among one third of NHL in the western world. DLBCL is common in elderly population. A 69-year-old postmenopausal woman who came with watery discharge since, 15 days was evaluated clinically and radiologically and was found to have thickened endometrium and enlarged ovaries, for which endometrial biopsy was taken that showed non-secretory endometrium with atrophic changes. Tumor markers found to be normal. TAH+BSO was done and the histopathology showed Non-Hodgkin’s lymphoma, diffuse large B cell type of the endometrium and both ovaries which was confirmed by immune histochemical marker study. PET-CT was done that showed metabolically active para aortic and common iliac lymph nodes thereby she was diagnosed with stage II (Ann Arbor Staging) non-Hodgkin’s lymphoma, hence she received 6 cycles of R-CHOP. As evident in our case, non-Hodgkin’s Lymphoma of the endometrium and the ovaries being an extremely rare condition, high-degree of suspicion is required for its prompt diagnosis and treatment.

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