Ibrutinib and idelalisib target B cell receptor- but not CXCL12/CXCR4-controlled integrin-mediated adhesion in Waldenstrom macroglobulinemia

Rooij, M F M de; Kuil, Annemieke; Kraan, Willem; Kersten, Marie José; Treon, Steven P.; Pals, Steven T.; Spaargaren, Marcel

doi:10.3324/haematol.2015.137265

Cited by 28 publications

(17 citation statements)

References 22 publications

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“…In keeping with this, it is noteworthy that IgM + BCR + plasma cells present striking phenotypical and functional similarities with the tumoural plasma cells responsible for Waldenström macroglobulinemia (WM) disease. Like WM cells, they express IgM and carry a functional BCR25, and have the propensity to produce CCL5 (ref. 26).…”

Section: Discussionmentioning

confidence: 99%

Mature IgM-expressing plasma cells sense antigen and develop competence for cytokine production upon antigenic challenge

et al. 2016

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Dogma holds that plasma cells, as opposed to B cells, cannot bind antigen because they have switched from expression of membrane-bound immunoglobulins (Ig) that constitute the B-cell receptor (BCR) to production of the secreted form of immunoglobulins. Here we compare the phenotypical and functional attributes of plasma cells generated by the T-cell-dependent and T-cell-independent forms of the hapten NP. We show that the nature of the secreted Ig isotype, rather than the chemical structure of the immunizing antigen, defines two functionally distinct populations of plasma cells. Fully mature IgM-expressing plasma cells resident in the bone marrow retain expression of a functional BCR, whereas their IgG+ counterparts do not. Antigen boost modifies the gene expression profile of IgM+ plasma cells and initiates a cytokine production program, characterized by upregulation of CCL5 and IL-10. Our results demonstrate that IgM-expressing plasma cells can sense antigen and acquire competence for cytokine production upon antigenic challenge.

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Section: Discussionmentioning

confidence: 99%

Mature IgM-expressing plasma cells sense antigen and develop competence for cytokine production upon antigenic challenge

et al. 2016

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“…However, alloHCT continues to have a role in select cases of high-risk aggressive WM/LPL. 14,19-24 This analysis of 144 patients is the largest series published to date on the use of alloHCT for WM/LPL and provides important insight into the anticipated outcomes for this therapeutic strategy.…”

Section: Discussionmentioning

confidence: 99%

Allogeneic Transplantation for Relapsed Waldenström Macroglobulinemia and Lymphoplasmacytic Lymphoma

Cornell

Bachanová

D’Souza

et al. 2017

Biology of Blood and Marrow Transplantation

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Waldenström macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL) is characterized by lymphoplasmacytic proliferation, lymph node and spleen enlargement, bone marrow involvement, and immunoglobulin M production. Treatment varies based on the extent and biology of disease. In some patients, the use of allogeneic hematopoietic cell transplantation (alloHCT) may have curative potential. We evaluated long-term outcomes of 144 patients that received adult alloHCT for WM/LPL. Data was obtained from the Center for International Blood and Marrow Transplant Research database (2001-2013). Patients received myeloablative (n=67) or reduced intensity conditioning (RIC; n=67). Median age at alloHCT was 53 years, and median time from diagnosis to transplantation was 41 months. Thirteen percent (n=18) failed prior autologous hematopoietic cell transplantation. About half (n=82, 57%) had chemo-sensitive disease at the time of transplantation, while 22% had progressive disease. Progression free survival, overall survival, rate of relapse, and non-relapse mortality at 5-years were 46%, 52%, 24%, and 30% respectively. Patients with chemo-sensitive disease and better pre-transplant disease status experienced significantly superior overall survival. There were no significant differences in progression-free survival based on conditioning (myeloablative 50% vs. RIC 41%) or graft source. Conditioning intensity did not impact treatment-related mortality or relapse. The most common causes of death were primary disease and graft-versus-host disease (GVHD). AlloHCT yielded durable survival in select patients with WM/LPL. Strategies to reduce mortality from GVHD and post-transplant relapse are necessary to improve this approach.

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“…It forms a covalent bond with a cysteine residue-Cys481 located at the rim of the ATP-binding pocket in BTK. Ibrutinib effectively inhibits cell cycle and proliferation, target BCR-controlled and chemokine-controlled-integrin-mediated adhesion, which results in lymphoma regression due to mobilization of the malignant cells from their protective niches into the circulation (87). Because BTK is expressed in non-T cell hematopoietic cell lineages, no toxic effects are exerted on T cells.…”

Section: Pvrl Treatmentmentioning

confidence: 99%

Case 01-2017—Primary vitreoretinal lymphoma (PVRL): report of a case and update of literature from 1942 to 2016

2018

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Primary vitreoretinal lymphoma (PVRL), as a subset of primary central nervous system lymphoma (PCNSL), is a rare and fatal ocular malignancy. Most PVRL masquerades as chronic posterior uveitis, which makes the clinical diagnosis challenging. Vitreous cells, subretinal lesions and imaging techniques are essential for clinical diagnosis. Importantly, cytopathology/histopathology identification of malignant cells is the gold standard for the diagnosis of PVRL. In addition, molecular detection of immunoglobulin heavy chain (IgH) or T cell receptor (TCR) gene rearrangements, immunophenotyping for cell markers, and cytokine analysis of interleukine-10 elevation are often used as adjunct procedures. Current management of PVRL involves local radiation, intravitreal chemotherapy (methotrexate and rituximab), with or without systemic chemotherapy depending on the involvement of non-ocular tissues. In cases with concomitant PCNSL, systemic high-dose methotrexate/rituximab based therapy in conjunction with local therapy, whole brain radiotherapy and/or autologous stem cell transplantation is considered. Although PVRL normally responds well to initial treatment, high rates of relapse and CNS involvement usually lead to poor prognosis and limited survival. A professional team of medical experts in ophthalmologists, ocular pathologists, neuro-oncologists and hemato-oncologists is essential for optimizing patient management.

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Ibrutinib and idelalisib target B cell receptor- but not CXCL12/CXCR4-controlled integrin-mediated adhesion in Waldenstrom macroglobulinemia

Cited by 28 publications

References 22 publications

Mature IgM-expressing plasma cells sense antigen and develop competence for cytokine production upon antigenic challenge

Mature IgM-expressing plasma cells sense antigen and develop competence for cytokine production upon antigenic challenge

Allogeneic Transplantation for Relapsed Waldenström Macroglobulinemia and Lymphoplasmacytic Lymphoma

Case 01-2017—Primary vitreoretinal lymphoma (PVRL): report of a case and update of literature from 1942 to 2016

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