Abstract:
:The proteasome inhibitor carfilzomib is highly effective in the treatment of multiple myeloma. It irreversibly binds the chymotrypsin-like active site in the β5 subunit of the 20S proteasome. Despite impressive response rates when carfilzomib is used in combination with immunomodulatory agents in newly diagnosed multiple myeloma patients; no biomarker exists to accurately predict response and clinical outcomes. We prospectively assessed the activity in peripheral blood of the chymotrypsin-like (CHYM), caspase-like (CASP) and trypsin-like (TRYP) proteolytic sites in 45 newly diagnosed multiple myeloma patients treated with eight cycles of carfilzomib, lenalidomide and dexamethasone (CRd) (NCT01402284). Samples were collected per protocol and proteasome activity measured through a fluorogenic assay. Median CHYM levels after one dose of carfilzomib decreased by >70%. CHYM and CASP activity decreased throughout treatment reaching a minimum after eight cycles of treatment. Higher levels of proteasome activity associated with higher disease burden (r > 0.30; p < 0.05) and higher disease stage (0.10 < p <0.20). No association was found with the probability of achieving a complete response, minimal residual disease negativity or time to best response. Further studies evaluating proteasome activity in malignant plasma cells may help elucidate how proteasome activity can be used as a biomarker in multiple myeloma.
journal_name
Leuk Lymphomajournal_title
Leukemia & lymphomaauthors
Manasanch EE,de Larrea CF,Zingone A,Steinberg SM,Kwok M,Tageja N,Bhutani M,Kazandjian D,Roschewski M,Wu P,Carter G,Zuchlinski D,Mulquin M,Lamping L,Costello R,Burton D,Gil LA,Figg WD,Maric I,Calvo KR,Yuan C,Stetdoi
10.1080/10428194.2016.1214953subject
Has Abstractpub_date
2017-03-01 00:00:00pages
639-645issue
3eissn
1042-8194issn
1029-2403journal_volume
58pub_type
杂志文章abstract::Mutations of the TP53 tumor suppressor gene, contributing to the development and progression of a wide variety of human malignancies, are found in some of the patients with myelodysplastic syndromes (MDS). Previous reports revealed that TP53 mutations were found in 0-25% of patients with MDS and are closely associated...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章,评审
doi:10.3109/10428199609054848
更新日期:1996-11-01 00:00:00
abstract::The aim of the study was efficacy and toxicity evaluation of combination of 2-Chlorodeoxyadenosine (2-CdA) with cytarabine (Ara-C) and G-CSF (CLAG regimen) as reinduction therapy in patients with refractory or relapsed acute myeloid leukemia (AML). The protocol stipulated an infusion of 5 mg/m2 of 2-CdA over 2 hours d...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.3109/10428190009053545
更新日期:2000-09-01 00:00:00
abstract::This phase-I/phase-II study evaluated panobinostat in combination with ifosfamide, carboplatin, etoposide (P-ICE) in relapsed/refractory classical Hodgkin lymphoma. During phase I, panobinostat was given daily on Monday/Wednesday/Friday starting one week prior to Cycle 1 (C1) of ICE and during two weeks of C1-2 of ICE...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章,随机对照试验
doi:10.1080/10428194.2017.1359741
更新日期:2018-04-01 00:00:00
abstract::The etiology of non-Hodgkin's lymphoma is unknown in the majority of the cases. Although Epstein-Barr virus, human T-cell leukemia-lymphoma virus and human herpes virus-8 have been established as casual agents in the pathogenesis of specific types of lymphoma, the role of hepatitis C virus (HCV) in lymphomagenesis rem...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章,评审
doi:10.1080/10428190400007771
更新日期:2004-12-01 00:00:00
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 a...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.1080/10428190310001639470
更新日期:2004-05-01 00:00:00
abstract::We performed a registry-based analysis of 311 AML patients treated with decitabine in a standard of care setting to assess response and survival data with a distinct focus on the impact of the TP53 mutation status. Median age was 73 years. 172 patients received decitabine first-line and 139 in r/r disease. The ORR (wh...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.1080/10428194.2020.1864354
更新日期:2021-01-05 00:00:00
abstract::There is little evidence about whether additional risk stratification for adult patients with acute lymphoblastic leukemia age 65 and older is warranted. Using the Surveillance, Epidemiology, and End Results data linked to Medicare claims, we examined the effects of age, comorbid conditions, and mobility limitations o...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.1080/10428194.2018.1555329
更新日期:2019-08-01 00:00:00
abstract::A leukemia-associated CD9 glycoprotein antigen released into the extracellular milieu from acute lymphoblastic leukemia cells has been detected using a unique lectin-monoclonal antibody immunoassay. It has been demonstrated that the release of CD9 antigen is an active process and is associated with active cell growth....
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::Post-transplant lymphoproliferative disorder (PTLD) caused by Epstein-Barr virus (EBV) is a severe complication in high-risk allogeneic hematopoietic stem cell transplant (HSCT) recipients. Central nervous system (CNS) involvement of PTLD is a very rare event in patients with HSCT. As no established standard therapy i...
journal_title:Leukemia & lymphoma
pub_type: 临床试验,杂志文章
doi:10.3109/10428194.2012.718342
更新日期:2013-03-01 00:00:00
abstract::Chronic myeloid leukemia (CML) is a hematopoietic stem cell disease with distinct biological and clinical features. The Philadelphia (Ph) chromosome and BCR/ABL fusion gene is the major cytogenetic and molecular marker of CML chronic phase. However, the molecular mechanisms of disease progression are not well known. R...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章,评审
doi:10.1080/10428190802163305
更新日期:2008-08-01 00:00:00
abstract::This study investigated expression profiles of tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) pathway components and mechanisms underlying TRAIL-induced apoptosis in mucosa associated lymphoid tissue (MALT) lymphoma. Genetic aberrations including translocations and trisomies were assessed by rev...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.3109/10428194.2014.953149
更新日期:2015-05-01 00:00:00
abstract::The quinazoline antifolate N-(5-[N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N- methylamino]-2-thenoyl)-L-glutamic acid (ZD1694; Tomudex) is a potent inhibitor of thymidylate synthase and causes cell death through disruption of DNA synthesis and repair by blocking the obligatory thymidine nucleotide synthesis....
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.3109/10428199809058358
更新日期:1998-02-01 00:00:00
abstract::We describe a patient with extranodal (pulmonary) marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) who was refractory to treatment with cytotoxic chemotherapy. After a single four-week course of rituximab she had significant regression of pulmonary lesions and remains progression free 19 month...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.1080/10428190500137890
更新日期:2005-09-01 00:00:00
abstract::We performed a phase II study of dexamethasone, ifosfamide, idarubicin and etoposide (DIZE) in patients with relapsed or refractory Hodgkin's (HL) and non-Hodgkin's lymphoma (NHL). The regimen consisted of dexamethasone (20 mg i.v. days 1-4), idarubicin (8 mg/m2 i.v. days 1+2), continuous infusion (c.i.) of ifosfamide...
journal_title:Leukemia & lymphoma
pub_type: 临床试验,杂志文章
doi:10.3109/10428199809059229
更新日期:1998-10-01 00:00:00
abstract::Leukemic lymphoblasts in B-lineage acute lymphoblastic leukemia (ALL) express morphologic, phenotypic and genotypic features which resemble those of B lymphocyte progenitors in normal bone marrow. Normal immature B cells and cells from most cases of B-lineage ALL rapidly die in vitro unless they are supported by bone ...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章,评审
doi:10.3109/10428199409049624
更新日期:1994-05-01 00:00:00
abstract::This study investigated the prognostic factors of Castleman disease (CD) and focused specifically on multicentric CD (MCD). Seventy patients with CD were studied. Forty-three patients (61.5%) had unicentric CD (UCD) and 27 patients (38.5%) had MCD. Thirty-six patients with UCD (83.7%) underwent surgical excision, and ...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.3109/10428194.2011.574759
更新日期:2011-08-01 00:00:00
abstract::Hodgkin lymphomas are characterised by the presence of rare malignant cells in a background of non-neoplastic inflammatory cells. Flow cytometric analysis of involved tissues is generally not thought to be useful in establishing the diagnosis, because of the small number of neoplastic cells present. However, two recen...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章,评审
doi:10.1080/10428190802308728
更新日期:2008-10-01 00:00:00
abstract::Interferon-gamma (IFN-gamma) exhibits various properties including antigrowth activity in neoplastic and normal cells and regulatory roles in immune responses and hematopoiesis, but studies of IFN-gamma effects on human megakaryopoiesis have been inconclusive. Recently we have used serum-free culture of purified CD34+...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章,评审
doi:10.3109/10428199809057590
更新日期:1998-09-01 00:00:00
abstract::Angiogenesis is a necessary step in solid tumor progression (growth, invasion and metastasis) with which it correlates and is indicative of an unfavourable prognosis. We observed bone marrow angiogenesis in patients with active multiple myeloma (MM), though not in patients with non-active MM nor with monoclonal gammop...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章,评审
doi:10.3109/10428199509054750
更新日期:1995-12-01 00:00:00
abstract::A 55-year-old Jewish patient was simultaneously diagnosed as having Gaucher's disease and IgA multiple myeloma. Serum protein electrophoresis and immunoelectrophoresis showed two different IgA kappa type monoclonal spikes. After four years of observation, a rapid fatal course of disease developed together with express...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.3109/10428199509054770
更新日期:1995-12-01 00:00:00
abstract::We addressed the prognostic impact of cell-of-origin (COO), MYC and Bcl-2 overexpression as well as isolated MYC rearrangement among 111 patients with limited stage diffuse large B-cell lymphoma (DLBCL) treated with consolidative radiation therapy (RT) after a metabolic complete response to immunochemotherapy. With a ...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.1080/10428194.2020.1869965
更新日期:2021-01-22 00:00:00
abstract::The occurrence of therapy-related acute lymphoblastic leukemia (ALL) is rare and, to our knowledge, is not reported in patients treated for Burkitt's leukemia. We report on a child with ALL with translocation t(4;11)(q21;q23) involving the MLL gene, 13 months after chemotherapy for Burkitt's leukemia. This present obs...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.1080/10428190500052248
更新日期:2005-06-01 00:00:00
abstract::The clinical features at time of diagnosis of long-term survivors with lymphoma type of adult T-cell leukemia (ATL) were compared with those of short-term survivors. We had 51 Japanese patients with lymphoma type of ATL from 1981 to 1989 who had human T-cell leukemia virus type I (HTLV-I) antibody and monoclonal integ...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.3109/10428199009106465
更新日期:1990-01-01 00:00:00
abstract::Intra-vascular lymphoma is usually reported as a rare and fatal disorder. We describe here the first case of an intra-vascular lymphoma revealed by a nephrotic syndrome for which a durable remission has been obtained by 8 cycles of bi-mensual CHOP and Rituximab therapy. In this report, 18 fluorodesoxyglucose tomoscint...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.1080/10428190410001683822
更新日期:2004-08-01 00:00:00
abstract::Large granular lymphocyte disorder (LGLD) is a lymphoproliferative disease, characterized by moderate lymphocytosis with an excess of large granular lymphocytes, neutropenia, anemia, and a variable, but mostly chronic clinical course. We describe two patients with LGLD. One patient presented with symptomatic corticost...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.3109/10428199109064883
更新日期:1991-01-01 00:00:00
abstract::Actinomycin D, a transcriptional inhibitor, was found to inhibit platelet potentiation by thrombopoietin (TPO), suggesting that TPO stimulation of platelets involves mitochondrial transcription. We sought to determine a possible role for leukemia-associated signal transducers and activators of transcription (STAT) pro...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.1080/1042819022386716
更新日期:2002-07-01 00:00:00
abstract::A rapid increase in incidence of non-Hodgkin lymphoma (NHL) has been reported from many countries. Exposure to certain pesticides and organochlorines has been shown to be risk factors. Epstein-Barr virus (EBV) is a human herpesvirus that has been associated with some subgroups of NHL, such as Burkitt lymphoma and lymp...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.3109/10428190109099322
更新日期:2001-08-01 00:00:00
abstract::The etiology of chronic lymphocytic leukemia (CLL) appears to be influenced by genetic factors which may contribute to its differential, gender- and age-specific incidence. The presented study is the first, which investigated the frequencies of DNA-typed alleles of all relevant human leukocyte antigens (HLA) loci in C...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.1080/10428190290021588
更新日期:2002-05-01 00:00:00
abstract::Primary myelosarcomas, also called leukemia cutis, granulocytic sarcomas or chloromas, are rare extramedullary manifestations of acute myeloid leukemia (AML) which precede bone marrow involvement. Skin infiltration was the most frequent localization associated with a myelomonocytic differentiation. Although first remi...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章,评审
doi:10.1080/10428190290012056
更新日期:2002-03-01 00:00:00
abstract::Tumour progression was monitored in seven multiple myeloma (MM) patients undergoing a novel oral chemotherapy regimen (cyclophosphamide, idarubicin and dexamethasone; CID) followed by early autologous stem cell transplantation (ASCT). Allele-specific oligonucleotide PCR (ASO-PCR) was used to semi-quantitate the number...
journal_title:Leukemia & lymphoma
pub_type: 临床试验,杂志文章,多中心研究
doi:10.3109/10428190109057937
更新日期:2001-01-01 00:00:00