Abstract:
:Current chemoimmunotherapy is unable to cure up to 40% of patients diagnosed with diffuse large B-cell lymphoma (DLBCL). Targeting the mechanisms by which DLBCL evades apoptosis is crucial to overcoming treatment failure in this heterogeneous disease as both current and novel treatments depend on the apoptosis of malignant cells. Despite the common overexpression of BCL-2, venetoclax is ineffective in DLBCL due to MCL-1 co-expression. This is driven by pro-growth PI3-kinase signaling, which is promoted in turn by PIM kinases. In this study, the novel dual-kinase inhibitor, IBL-202, was combined with venetoclax against a panel of DLBCL cell lines that have variable expression of pro-survival proteins. The results support the efficacy of simultaneously targeting inter-related molecules to overcome apoptotic escape in this biologically heterogeneous disease. As venetoclax, pan-PIM-kinase and pan-PI3-kinase inhibitors have, or are currently being studied in clinical trials, it may be rational to consider these drugs in combination for the treatment of DLBCL.
journal_name
Leuk Lymphomajournal_title
Leukemia & lymphomaauthors
Gifford G,Stevenson W,Best Gdoi
10.1080/10428194.2020.1795156subject
Has Abstractpub_date
2020-12-01 00:00:00pages
3165-3176issue
13eissn
1042-8194issn
1029-2403journal_volume
61pub_type
杂志文章abstract::Rituximab (IDEC C2B8) is a chimeric human-mouse monoclonal anti-CD20 antibody that has been proven to be effective for the treatment of patients with CD20 positive leukemia and lymphoma. The level of CD20-expression in patients with B-cell chronic lymphocytic leukemia (B-CLL) is low in comparison to other B-cell lymph...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.1080/10428190210178
更新日期:2002-01-01 00:00:00
abstract::The insulin-like growth factor (IGF) system regulates proliferation and differentiation of hematopoietic cells. IGFs exert their effects through specific receptors on growing and differentiating blood cells as they emerge from their small pool of ancestral stem cells. The IGF system is complex as both stimulating and ...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章,评审
doi:10.1080/10428190290011958
更新日期:2002-03-01 00:00:00
abstract::The relationship between histopathologic characteristics and treatment outcomes in patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab-based immunochemotherapy needs re-evaluation. Patients with newly diagnosed DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednis...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.3109/10428194.2011.588761
更新日期:2011-10-01 00:00:00
abstract::Primary non-Hodgkin's lymphoma of bone is uncommon and usually manifests clinically as localized bone pain. Here we report a woman who presented with hypercalcemic crisis and extensive investigation revealed a primary multifocal lymphoma of bone. The course of the disease was very aggressive and despite intensive supp...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.3109/10428199909083398
更新日期:1999-06-01 00:00:00
abstract::INHBA (inhibin βA), a subunit of a ligand of the transforming growth factor-β superfamily, is known to play diverse roles in various solid tumors. However, its role in hematologic malignancies remains unexplored. Here, we investigated the function of INHBA in diffuse large B-cell lymphoma (DLBCL). Both mRNA and protei...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.1080/10428194.2017.1372574
更新日期:2018-05-01 00:00:00
abstract::Follicular lymphoma (FL) is characterized by an initial response to treatment with inevitable relapse. We evaluated chemoimmunotherapy resistance (CIR resistance) including transformation. We identified patients who received rituximab combination therapy for symptomatic FL. CIR resistance was defined as disease progre...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.3109/10428194.2014.885513
更新日期:2014-11-01 00:00:00
abstract::Myeloproliferation, myeloaccumulation (decreased apoptosis), inflammation, bone marrow fibrosis and angiogenesis are cardinal features of the Philadelphia-negative chronic myeloproliferative neoplasms: essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF). Histone deacetylases (HDACs) ...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.3109/10428194.2011.597905
更新日期:2012-01-01 00:00:00
abstract::Endoglin (CD105) is a component of the transforming growth factor-beta (TGF-beta) receptor (TGF-betaR) complex. Together with betaglycan, CD105 is considered as a TGF-betaR accessory molecule (also called TGF-betaRIII), but its functions in the receptor-ligand interactions are still poorly understood. A small subset o...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章,评审
doi:10.3109/10428190109097744
更新日期:2001-11-01 00:00:00
abstract::Chronic lymphocytic leukemia (CLL) is a neoplastic disorder of mature B lymphocytes. While traditionally treated with combinations of chemoimmunotherapy, the therapeutic options for CLL have expanded in recent years with the emergence of novel oral agents, such as the Bruton tyrosine kinase inhibitor ibrutinib, that a...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章,评审
doi:10.1080/10428194.2017.1280606
更新日期:2017-06-01 00:00:00
abstract::There is insufficient information on the characteristics of chronic lymphocytic leukemia (CLL) in Latin American patients. Immunoglobulin variable-region heavy-chain (IGVH) gene usage and mutation status and prognostic factors were investigated in patients resident in Venezuela. The most frequently used IGVH family ge...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.3109/10428194.2011.606938
更新日期:2012-02-01 00:00:00
abstract::Acute graft versus host disease (aGVHD) was first described by Barnes et al. in 1962, who reported a 'secondary disease' in mice after irradiation and infusion of allogeneic spleen cells. The disease manifested as fatal diarrhea and skin abnormalities. They postulated that aGVHD resulted from introducing immunological...
journal_title:Leukemia & lymphoma
pub_type: 评论,杂志文章
doi:10.1080/10428194.2019.1613545
更新日期:2019-09-01 00:00:00
abstract::Syndecan-1 is a transmembrane proteoglycan expressed on the surface of tumor cells of various origins including myeloma, Hodgkin's disease, and certain human immunodeficiency virus (HIV) associated lymphomas. Functional studies in myeloma reveal that syndecan-1 may act as a multifunctional regulator of cell behavior i...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章,评审
doi:10.3109/10428199909083378
更新日期:1999-06-01 00:00:00
abstract::Severe myelosuppression is one of the major adverse effects of Idarubicin (IDA). Especially, after two sequential therapy courses, IDA showed a stronger myelosuppression than after the first course. IDA was metabolized in liver by carbonyl reducing enzymes (CRE) to its 13-OH metabolite, idarubicinol(IDAol),which is mo...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.1080/10428190801947526
更新日期:2008-04-01 00:00:00
abstract::Eighteen patients (pts) with myelodysplastic syndrome (MDS) were treated with thymopentin (TP) (50 mg subcutaneously for 5 days) and recombinant interferon alpha 2a (rIFN alpha 2a) (3 MU/m2 subcutaneously on the sixth day); the courses were delivered every week. Moreover those pts with > or = 10% blasts in the bone ma...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.3109/10428199509049773
更新日期:1995-01-01 00:00:00
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journal_title:Leukemia & lymphoma
pub_type: 杂志文章,评审
doi:10.1080/10428194.2018.1485914
更新日期:2019-02-01 00:00:00
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journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.1080/10428194.2020.1768382
更新日期:2020-10-01 00:00:00
abstract::The association of chronic lymphocytic leukemia (CLL) with essential thrombocythemia (ET) is an extremely rare event and until now 3 patients with such coexistence have been reported in the literature. We report a 77-year-old white woman in whom these two disorders were diagnosed concomitantly on the basis of peripher...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章,评审
doi:10.1080/1042819031000097348
更新日期:2003-08-01 00:00:00
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journal_title:Leukemia & lymphoma
pub_type: 杂志文章,随机对照试验
doi:10.3109/10428194.2015.1106534
更新日期:2016-07-01 00:00:00
abstract::The induction of apoptosis following topoisomerase inhibitors proceeds in at least three distinct steps: (1) induction of cleavable complexes (potentially lethal damage), (2) topoisomerase-induced DNA damage, and (3) a presently unknown sequence of events that must either lead to cell cycle arrest (G2-block, different...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章,评审
doi:10.3109/10428199409051674
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journal_title:Leukemia & lymphoma
pub_type: 杂志文章,评审
doi:10.3109/10428190903288514
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journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.1080/10428194.2020.1788015
更新日期:2020-08-01 00:00:00
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journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.3109/10428199209053608
更新日期:1992-05-01 00:00:00
abstract::A two-year-old girl presented with a 3-month history of generalized pruritus. One week before hospitalization she developed a superior vena cava syndrome and obstruction of the upper airways. Clinical and laboratory findings included generalized lymphadenopathy, a mediastinal mass compressing the tracheal lumen to the...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.1080/1042819021000006330
更新日期:2002-09-01 00:00:00
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journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.3109/10428190903586326
更新日期:2010-05-01 00:00:00
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journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.1080/10428190601101001
更新日期:2007-02-01 00:00:00
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journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.3109/10428199909058457
更新日期:1999-05-01 00:00:00
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journal_title:Leukemia & lymphoma
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更新日期:2004-11-01 00:00:00
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journal_title:Leukemia & lymphoma
pub_type: 杂志文章,评审
doi:10.3109/10428199409073777
更新日期:1994-02-01 00:00:00
abstract::The standard CHOP regimen may cure 30-40% of patients with advanced aggressive non-Hodgkin's lymphoma (ANHL). Mitoxantrone is an anthracenedione, which is active in NHL and its toxicity profile may be more favorable than doxorubicin with respect to alopecia, mucositis and cardiotoxicity. This study was designed to com...
journal_title:Leukemia & lymphoma
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1080/1042819031000063471
更新日期:2003-04-01 00:00:00
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journal_title:Leukemia & lymphoma
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doi:10.3109/10428199709050899
更新日期:1997-08-01 00:00:00