Abstract:
:Bryostatin, a macrocyclic lactone and protein kinase C (PKC) modulator, has been shown to have differentiation and anti-tumor activity against several leukemia cell lines in vitro. In this study, we demonstrated Bryostatin-induced differentiation in B-cell chronic lymphocytic leukemia (B-CLL) cells, characterized by an increase in cell size and a marked up-regulation of CD11c expression. The specific inhibitors of the extracellular signal-regulated kinase (ERK) and protein kinase C pathways, PD98059 and GF 109203X respectively, each completely blocked Bryostatin-induced differentiation of B-CLL cells, suggesting that activation of the ERK pathway plays a direct role in this process in a PKC-dependent manner. Furthermore, Bryostatin reduced both spontaneous and drug-induced apoptosis with chlorambucil, fludarabine and 2-chloro-2'-deoxyadenosine (2-Cda) in B-CLL cells. This resistance was associated with an early up-regulation of the anti-apoptotic protein Mcl-1 and post-translational phosphorylation of Bcl-2 at serine 70. The anti-apoptotic effects of Bryostatin were abrogated by GF 109203X, and to a lesser extent by the phosphatidylinositol 3-kinase (PI3-kinase) inhibitor, LY294002. Interestingly, the ERK inhibitor, PD98059 inhibited Mcl-1 expression but had little effect on Bryostatin-induced survival suggesting that the ERK pathway predominantly affects differentiation. Taken together these results present an explanation for Bryostatin-induced B-CLL cell survival in which modulation of the PKC pathway couples differentiation with an increase in antiapoptotic protein expression and calls into question the rationale for its use in the treatment of B-CLL.
journal_name
Leuk Lymphomajournal_title
Leukemia & lymphomaauthors
Thomas A,Pepper C,Hoy T,Bentley Pdoi
10.1080/10428190310001639470keywords:
subject
Has Abstractpub_date
2004-05-01 00:00:00pages
997-1008issue
5eissn
1042-8194issn
1029-2403journal_volume
45pub_type
杂志文章abstract::Chronic myeloid leukemia (CML) is rare among children and adolescents. The early molecular response (EMR) is an important prognostic significance for adult CML patients. This study explored the impact of EMR on the prognosis in 40 children and adolescents with CML-CP treated with imatinib (IM). Our results showed that...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.1080/10428194.2017.1422860
更新日期:2018-09-01 00:00:00
abstract::During the last few years it has been shown that intensive or continuing chemotherapy of patients with advanced chronic lymphocytic leukemia prolongs survival. In the search for new effective drugs with tolerable toxicity, mitoxantrone was evaluated in this phase 2 study. Seven of 11 previously untreated patients achi...
journal_title:Leukemia & lymphoma
pub_type: 临床试验,杂志文章
doi:10.3109/10428199209049782
更新日期:1992-07-01 00:00:00
abstract::Leukemia is a result of accumulating genetic alterations. The collaboration of mutations that offer survival and proliferative signals, together with mutations that result in lack of differentiation, is thought to cause a leukemic phenotype. The cyclic-AMP Response Element Binding Protein (CREB) is a transcription fac...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章,评审
doi:10.1080/1042819031000151095
更新日期:2004-02-01 00:00:00
abstract::Anamorsin is a cell-death-defying factor, which was originally isolated as a molecule that conferred resistance to apoptosis induced by growth factor starvation. In order to evaluate anamorsin expression levels in malignant lymphoma, we immunostained paraffin-embedded sections with anti-anamorsin monoclonal antibodies...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.1080/10428190701713697
更新日期:2008-01-01 00:00:00
abstract::The NK-like family of homeobox genes includes TLX1, TLX3 and NKX2-5, which are ectopically activated in distinct subsets of T-cell acute lymphoblastic leukemia (T-ALL) cells. Here we analysed their effect on the miR-17-92 cluster overexpressed in several types of cancer, including T-ALL. The pri-miR-17-92 polycistron ...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.1080/10428190802626632
更新日期:2009-01-01 00:00:00
abstract::Rituximab maintenance (RM) improves time to progression (PFS) in advanced follicular lymphoma (FL), but the impact of various RM schedules remains unknown. This study performed a retrospective evaluation of RM given for up to 2 years vs observation in 319 untreated FL patients (stage II-IV; grade 1-3A) responding to R...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章,多中心研究
doi:10.3109/10428194.2015.1079313
更新日期:2016-05-01 00:00:00
abstract::Donor T cells have a critical role in promoting engraftment after allogeneic bone marrow transplantation (BMT), but also cause graft versus host disease (GVHD). Ex vivo T cell depletion has been an effective strategy to reduce GVHD but has been associated with impaired alloengraftment and host immunity. Using an MHC-m...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.1080/1042819021000016041
更新日期:2002-10-01 00:00:00
abstract::Conditions associated with abnormal B-cell proliferation have an increased incidence in the HIV-infected population. A longitudinal study conducted at the Tulane Regional Primate Research Center has followed more than 1,000 rhesus macaques infected with simian-immunodeficiency virus (SIV) since 1984. While spontaneous...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.3109/10428190009058522
更新日期:2000-05-01 00:00:00
abstract::Multiple genes have been identified to cause hereditary predispositions to hematologic malignancies, and characterized by an increased risk to develop myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and/or aplastic anemia (AA). Referral algorithms for patients who may be at higher risk have been propose...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.1080/10428194.2019.1630618
更新日期:2019-12-01 00:00:00
abstract::We report a case of Epstein-Barr virus (EBV)-associated lymphoproliferative disorder (LPD) which developed after chemotherapy for hemophagocytic lymphohistiocytosis (HLH), who had no history of immunodeficiency or familial X-linked LPD. In HLH, the presence of EBV in T-cells was confirmed by a combination of in situ h...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.3109/10428190009058512
更新日期:2000-05-01 00:00:00
abstract::To explore the feasibility and potential advantages of PBSC in allogeneic transplantation, we grafted 24 patients (age 16-57, median 37) with different hematologic diseases (ALL = 10, AML = 5, MM = 4, NHL = 2, CML = 1, MDS = 1, AA = 1), 23 HLA-identical to their siblings and 1 partially matched. Cells were collected f...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.3109/10428199709058600
更新日期:1997-12-01 00:00:00
abstract::We attempted to analyze whether the use of high-dose cyclophosphamide (CTX 7g/m2, group A) plus hematopoietic growth factor (G-CSF) or G-CSF alone (10 microg/Kg, group B) as a mobilizing regimen, could result in harvesting different numbers of CD34+ cells, committed progenitors and CD34+ cells subsets. The number of C...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.3109/10428190009065829
更新日期:2000-10-01 00:00:00
abstract::We aimed to investigate whether the clinical characteristics, the rate of treatment demand and survival differ between chronic lymphocytic leukemia (CLL) patients <65 years (y) and ≥65 y. Sixty three (46%) patients were <65 y and 74 (54%) were ≥65 y. 28.6% (18/63) of the patients <65 required treatment, while this rat...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.1080/10428194.2018.1509316
更新日期:2019-03-01 00:00:00
abstract::In order to assess the contribution of FC to the diagnosis of lymph node disorders we retrospectively compared the pathological and the FC diagnosis made in 118 consecutive lymph node biopsies. Pathological diagnosis included non malignant conditions (n = 43), B-cell Non Hodgkin lymphoma (NHL) (n = 30), T-cell NHL (1 ...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.1080/10428190310001609906
更新日期:2004-08-01 00:00:00
abstract::Immunomodulatory drugs (IMiDs) may favor autoimmune disease (AD) occurrence. We conducted a retrospective study to evaluate AD occurrence among IMiD-treated patients with myeloma. Patients were grouped into three classes depending on the type of IMiD engaged. The first group included patients treated with thalidomide ...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.3109/10428194.2014.914203
更新日期:2014-09-01 00:00:00
abstract::Adult T-cell leukemia/lymphoma (ATLL) remains an uncommon disorder outside well-defined risk groups. We describe the case of an Iranian woman, who presented with isolated meningeal relapse of diffuse large-cell lymphoma. The malignant cells coexpressed CD4 and CD8 and HTLV-1 seropositivity was confirmed. Despite combi...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.3109/10428199409073790
更新日期:1994-02-01 00:00:00
abstract::Nucleoside analogs are important components of treatment regimens for acute leukemia in adults. Plasma membrane permeation of the nucleoside analog molecules, the initial event in the cellular conversion of nucleosides to active agents, is mediated by nucleoside-specific membrane transporters. The widely-expressed es ...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章,评审
doi:10.3109/10428199809059245
更新日期:1998-12-01 00:00:00
abstract::Following the initial success of imatinib as frontline therapy for chronic myeloid leukemia (CML), several second-generation therapeutics have been developed with increased potency and the ability to inhibit the majority of imatinib-resistant mutations. Here, we review the current knowledge about the target specificit...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章,评审
doi:10.1080/10428190801896103
更新日期:2008-04-01 00:00:00
abstract::Hairy cell leukemia (HCL) is a rare B-cell lymphoproliferative disorder, but is gratifying to treat for both physicians and patients. During the 50 years since its initial description as a clinical entity, hematologists have been fascinated by the bizarre appearance of the malignant cell with its hair-like projections...
journal_title:Leukemia & lymphoma
pub_type: 历史文章,杂志文章,评审
doi:10.3109/10428190903219667
更新日期:2009-10-01 00:00:00
abstract::Even though amphotericin B is associated with considerable hematological toxicity, this subject has been poorly studied. This retrospective cohort study assessed the incidence and predictors of hematological toxicity in patients treated with different amphotericin B formulations: amphotericin B deoxycholate (d-AmB), l...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.3109/10428194.2015.1010080
更新日期:2015-01-01 00:00:00
abstract::This retrospectively collected laboratory-based surveillance data includes 575 healthcare-associated bloodstream infections (BSIs) in 350 patients with hematological malignancy in Tampere University Hospital, Finland, during 1999-2001 and 2005-2010. The most common underlying diseases were acute myelogenous leukemia (...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.3109/10428194.2015.1032967
更新日期:2015-01-01 00:00:00
abstract::There is an abundance of data dealing with recirculation of T cells in the rats, but relatively little is known about the traffic of B cells. The adhesion molecules expressed on the surface membrane are of great significance for recirculation of lymphocytes. However, very little is known about the expression of variou...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章,评审
doi:10.1080/1042819021000033006
更新日期:2002-11-01 00:00:00
abstract::The humanized monoclonal antibody Hu1D10 (Remitogen, Protein Design Labs, Fremont, CA) recognizes a polymorphic determinant of human leukocyte antigen-DR expressed on the majority of B-cell lymphomas and on normal B cells of most individuals. Hu1D10 mediates complement-mediated cytotoxicity, antibody-dependent cell-me...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.1080/10428190290026376
更新日期:2002-06-01 00:00:00
abstract::A better understanding of events triggering chronic myeloid leukemia progression is critical for optimized clinical management of chronic myeloid leukemia (CML). We sought to validate that increased expression of Musashi 2 (MSI2), a post-transcription regulator, is associated with progression and prognosis. Screening ...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.3109/10428194.2014.981175
更新日期:2015-07-01 00:00:00
abstract::Considering conflicting data on CDKN2A/B deletion in ALL, this study to assess its prognostic significance as an independent marker in a total of 96 pediatric B and T-ALL cases was planned. The overall frequency of CDKN2A/B deletion was 44% (n = 43) with 36% (30/83) in B-ALL and 100% (13/13) in T-ALL. CDKN2A/B deletio...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.1080/10428194.2018.1482542
更新日期:2019-02-01 00:00:00
abstract::To identify epigenetically silenced miRNAs and to investigate their influences on predictive target oncogenes in extranodal natural killer/T-cell lymphoma (NKTCL). Decitabine treatment was performed to evaluate methylated miRNAs in NKTCL cells. The relationship between a given miRNA and its target mRNA was validated u...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.1080/10428194.2019.1654096
更新日期:2020-01-01 00:00:00
abstract::There is increasing evidence for an interaction between acute leukemia cells and the microenvironment of the bone marrow. Blast cells from cases of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) bind to cellular and extracellular matrix components of the bone marrow stroma. In AML, adhesion to str...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章,评审
doi:10.3109/10428199509064917
更新日期:1995-06-01 00:00:00
abstract::Bullous pyoderma gangrenosum begins as a bulla, nodule or nonulcerated erythematous plaque that blisters or ulcerates to form a superficial ulcer surrounded by a hemorrhagic, bullous border, which is surrounded by a blue-gray halo. Bullous pyoderma gangrenosum is most commonly associated with hematologic malignancies,...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.1080/10428190500254299
更新日期:2006-01-01 00:00:00
abstract::Conventional cytogenetic analysis is limited in the evaluation of plasma cell disorders because, relative to normal hematopoietic elements, plasma cells divide slowly. Moreover, it is difficult to know whether abnormal metaphases originate from malignant plasma cells or myeloid cells harboring other abnormalities. We ...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.3109/10428190009065839
更新日期:2000-10-01 00:00:00
abstract::The Philadelphia chromosome, arising as a consequence of the t(9;22) translocation, is one of the most frequent and certainly the most known cytogenetic abnormality present in human hematological malignancies. Unlike the vast majority of the other translocations, its presence is not restricted to a specific leukemia p...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章,评审
doi:10.3109/10428199709051777
更新日期:1997-07-01 00:00:00