Abstract:
:The introduction of novel immunomodulatory drugs (IMiDs) has dramatically improved the survival of patients with multiple myeloma (MM). While it has been shown that patients with specific cytogenetic subtypes, namely t(4;14), have the best outcomes when treated with bortezomib-based regimens, the relationship between cytogenetic subtypes and response to IMiDs remains unclear. Using DNA synthesis assays, we investigated the relationship between cytogenetic subtype and lenalidomide response in a representative panel of human myeloma cell lines (HMCLs). We examined HMCL protein expression levels of the lenalidomide target cereblon (CRBN) and its downstream target interferon regulatory factor-4 (IRF4), which have previously been shown to be predictive of lenalidomide response in HMCLs. Our results reveal that lenalidomide response did not correlate with specific cytogenetic translocations. There were distinct groups of lenalidomide-responsive and non-responsive HMCLs, as defined by inhibition of cellular proliferation; notably, all of the hyperdiploid HMCLs fell into the latter category. Repeated dosing of lenalidomide significantly lowered the IC50 of the responsive HMCL ALMC-1 (IC50 = 2.6 μm vs. 0.005 μm, P < 0.0001), but did not have an effect on the IC50 of the non-responsive DP-6 HMCL (P > 0.05). Moreover, no association was found between lenalidomide responsiveness and CRBN and IRF4 expression. Our data indicate that lenalidomide sensitivity is independent of cytogenetic subtype in HMCLs. While CRBN and IRF4 have been shown to be associated with response to lenalidomide in patients, these findings do not translate back to HMCLs, which could be attributable to factors present in the bone marrow microenvironment.
journal_name
Eur J Haematoljournal_title
European journal of haematologyauthors
Greenberg AJ,Walters DK,Kumar SK,Rajkumar SV,Jelinek DFdoi
10.1111/ejh.12192subject
Has Abstractpub_date
2013-12-01 00:00:00pages
504-13issue
6eissn
0902-4441issn
1600-0609journal_volume
91pub_type
杂志文章abstract:OBJECTIVES:The role of high-dose therapy and autologous stem-cell transplantation (HDT/ASCT) in the up-front treatment of poor-risk aggressive lymphoma is still unknown. We conducted a prospective multi-centre trial with dose-escalated CHOP (MegaCHOP) and tailored intensification prior to HDT/ASCT according to early re...
journal_title:European journal of haematology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1111/j.1600-0609.2007.01020.x
更新日期:2008-03-01 00:00:00
abstract::Iron overload (IO) in the heart is a life-threatening complication in transfusion-dependent patients with thalassaemia major (TM) and to a lesser extent in sickle cell disease (SCD), while no data are available in patients with sickle/beta(0)-thalassaemia. Iron deposition in the heart, liver and pancreas was assessed ...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.2009.01355.x
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:Although allogeneic hematopoietic cell transplantation (HCT) has a potential to cure patients with paroxysmal nocturnal hemoglobinuria (PNH), appropriate indication and conditioning regimen for HCT have not been established. PATIENTS AND METHODS:Between July 1999 and December 2001, five patients with PNH un...
journal_title:European journal of haematology
pub_type: 临床试验,杂志文章
doi:10.1034/j.1600-0609.2003.00097.x
更新日期:2003-08-01 00:00:00
abstract::We describe a case of acute promyelocytic leukemia in a 61-yr-old woman with a cryptic insertion of RARA gene into PML gene. Using a combination of cytogenetic and molecular methods, we confirmed the insertion and presence of the PML-RARA transcript and lack of the reciprocal RARA-PML transcript. Although such cryptic...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/ejh.12326
更新日期:2014-10-01 00:00:00
abstract::Spontaneous remission in patients with acute myeloid leukemia (AML) is a rarely reported phenomenon of usually short duration. The etiology remains unclear, but an association with preceding blood transfusions or bacterial infections has been reported. Triggered immune responses are suggested to play a potential role ...
journal_title:European journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/j.1600-0609.2004.00248.x
更新日期:2004-07-01 00:00:00
abstract::Upshaw-Schulman syndrome (USS) is due to severe congenital deficiency of von Willebrand factor (VWF)-cleaving protease ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 domains, nr 13) activity resulting in the presence of unusually large forms of VWF in the circulation, causing intravascular plat...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/ejh.12197
更新日期:2014-02-01 00:00:00
abstract:INTRODUCTION/OBJECTIVES:Acute myeloid leukemia (AML) accounts for 90% of all cases of acute leukemia in adults. In Brazil, the mortality from myeloid leukemia is 1.74/100 000 men and 1.37/100 000 women. Our aim was to review and update guidelines of the Brazilian Society of Bone Marrow Transplantation on indications of...
journal_title:European journal of haematology
pub_type: 杂志文章,实务指引
doi:10.1111/ejh.12808
更新日期:2017-02-01 00:00:00
abstract::Monoclonal antibodies 8A and 62B1, recognizing plasma cell-associated antigens, were covalently linked to saporin 6, a ribosome-inactivating protein similar to the A-chain of ricin. Both immunotoxins were tested on target human cell lines U266 and Raji, on non-target K562 cell line and on myeloid CFU-GM progenitors. T...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.1989.tb00105.x
更新日期:1989-03-01 00:00:00
abstract::Auto-immune haemolytic anaemia (AIHA) is characterised by haemolysis associated with the presence of the immunoglobulins IgG, IgM or IgA, and/or components of the complement system on the red cell membrane. The immunoglobulins react as auto-antibodies against the red cell antigens of the patient. IgG antibodies and th...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1034/j.1600-0609.2003.02846.x
更新日期:2003-01-01 00:00:00
abstract:OBJECTIVES:Some patients with myelodysplastic syndrome (MDS) show a marked increase in the percentage of immature platelet fraction (IPF%) despite the absence of severe thrombocytopenia. To determine the significance of such an unbalanced increase in the IPF%, we investigated the IPF% and other laboratory findings of 5...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.2008.01156.x
更新日期:2009-01-01 00:00:00
abstract::Between December, 1984, and May, 1986, 98 CSF samples were sent to a central laboratory by postal express. The samples could be kept in a medium for up to 24 hours after the lumbar puncture. The quality of the cells proved to be good. Excluded were 5 samples delayed in delivery and 13 samples contaminated with blood, ...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.1988.tb00832.x
更新日期:1988-03-01 00:00:00
abstract::Immune reconstitution may be delayed after CD34-selected compared with unmanipulated autologous peripheral blood stem cell transplantation (PBSCT), resulting in a theoretically increased risk of infections. In a case-control matched study we compared the incidence of infection in 25 recipients of CD34-selected PBSC (C...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.2005.00569.x
更新日期:2006-02-01 00:00:00
abstract:OBJECTIVE:To correlate the clinical and hematological features of β-globin gene haplotypes with the oxidative stress status in pediatric patients with sickle cell disease (SCD). METHODS:A total of 95 patients with SCD and 40 healthy children were studied. The β-globin cluster, plasma lipid peroxidation (LPO) and plasm...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.2010.01528.x
更新日期:2010-12-01 00:00:00
abstract:OBJECTIVE:Patients with hematologic malignancies are at substantial risk of developing invasive fungal infections (IFI) that are associated with substantial morbidity and mortality. This article reviews the epidemiology, risk factors, and efficacy of antifungal prophylaxis in patients with hematologic malignancies. ME...
journal_title:European journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/j.1600-0609.2006.00805.x
更新日期:2007-04-01 00:00:00
abstract::Bcl-2 expression, the number of apoptotic cells and the growth and differentiation of early bone marrow progenitor cells were studied in patients with confirmed diagnosis of acute myeloid leukaemia (AML). Bone marrow cells from normal individuals were used as controls. We observed an increased percentage of bcl-2-mono...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.1999.tb01112.x
更新日期:1999-01-01 00:00:00
abstract::Cardiac disease is the primary cause of mortality in beta-thalassemia patients. Except for ventricular dysfunction and pulmonary hypertension that represent the main forms of heart disease in these patients, valvular abnormalities including valvular regurgitation, endocardial thickening and calcification and mitral va...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.2004.00213.x
更新日期:2004-04-01 00:00:00
abstract:AIMS:Aim of the study is to investigate diffuse large B-cell lymphoma (DLBCL) for the presence of BCL3 gene rearrangement and protein expression and to correlate these with immunophenotypic subsets of DLBCL. We aimed to investigate the pathogenetic implication of BCL3 in DLBCL. METHODS AND RESULTS:Tissue microarray se...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.2011.01684.x
更新日期:2011-12-01 00:00:00
abstract::Isolated myeloid sarcoma is a rare presentation of acute myeloid leukemia. There are limited data available concerning the prognostic relevance and the right treatment strategy for this clinical scenario. Here, we report a case of acute myeloid leukemia with extensive lesions and fractures in multiple bones in a 64-yr...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/ejh.12254
更新日期:2014-06-01 00:00:00
abstract::Neonatal alloimmune thrombocytopenia (NAIT) occurs because of transplacentally acquired maternal platelet alloantibodies. Most of the alloantibodies are against human platelet antigens, but the alloantibody against CD36 is rare. A full-term female baby was delivered by a mother who experienced two spontaneous abortion...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.2008.01093.x
更新日期:2008-07-01 00:00:00
abstract::The effect of rhIL-3 was investigated in 32 patients with newly diagnosed non-Hodgkin lymphoma in a phase I/II trial. All patients received 6 cycles of standard CHOP chemotherapy, and each patient was his own control where rhIL-3 was given as a daily s.c. injection for 14 days (day 2-15) in cycle 2 and 4, while cycle ...
journal_title:European journal of haematology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1600-0609.1995.tb01772.x
更新日期:1995-02-01 00:00:00
abstract:BACKGROUND:Most viral infections are known to exert adverse effects on bone marrow function. However, certain viruses have recently been found to be therapeutically beneficial in the treatment of some malignant disorders. METHODS AND MATERIALS:A retrospective study was conducted at the Armed Forces Hospital, Riyadh, S...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.2005.00504.x
更新日期:2005-09-01 00:00:00
abstract::Copper deficiency is an established cause of hematological abnormalities but is frequently misdiagnosed. Copper deficiency can present as a combination of hematological and neurological abnormalities and it may masquerade as a myelodysplastic syndrome. We reviewed the records of patients with hypocupremia and hematolo...
journal_title:European journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/j.1600-0609.2008.01050.x
更新日期:2008-06-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Minimal residual disease (MRD) assessment by PCR in multiple myeloma (MM) has several shortcomings, including the lack of a suitable target. Kappa deleting element (KDE) rearrangements occur in virtually all Ig-lambda B-cell malignancies and in 1/3 of Ig-kappa are not affected by somatic hyper...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/ejh.12000
更新日期:2012-10-01 00:00:00
abstract:OBJECTIVE:Myelodysplastic syndromes (MDS) and aplastic anemia (AA) are the most common anemias that require transfusion therapy in Japan. This retrospective survey investigated relationships between iron overload, chelation practices, and morbidity/mortality in patients with these diseases. METHOD:Medical histories of...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.2007.00842.x
更新日期:2007-06-01 00:00:00
abstract:OBJECTIVES:Cord blood (CB) transplantation has advantages in terms of incidence and severity of acute graft-versus-host disease (GVHD), while it has disadvantages in terms of infection. Our aim is to elucidate the molecular mechanism underlying the immune response of CB-derived cells during acute GVHD and infection fol...
journal_title:European journal of haematology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1600-0609.2011.01707.x
更新日期:2012-01-01 00:00:00
abstract:PURPOSE:To estimate the clinical significance of low serum concentrations of mannose-binding lectin (MBL) in patients with acute myeloid leukaemia (AML) during initial cancer chemotherapy. PATIENTS AND METHODS:80 consecutive, newly diagnosed, and unselected AML patients (age 18-77 yr) undergoing remission induction ch...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1034/j.1600-0609.2003.00012.x
更新日期:2003-02-01 00:00:00
abstract:OBJECTIVES:Anthracyclines and cytarabine are cornerstones for intensive chemotherapy in acute myeloid leukemia (AML). The goals of this study were to comprehensively assess deviations from theoretical doses and the impact of body-surface area (BSA) on patients' characteristics, physicians' strategy, dose adjustment, an...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/ejh.12850
更新日期:2017-05-01 00:00:00
abstract:OBJECTIVES:Myeloma bone disease is a result of excessive osteoclast activation and impaired osteoblast function. Recent in vitro studies suggested that proteasome inhibitors might increase osteoblast function. METHODS:We analyzed serum markers of osteoblast activity in 25 patients with multiple myeloma receiving borte...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.2006.00692.x
更新日期:2006-09-01 00:00:00
abstract::A transgenic SCID (TG-SCID) mouse expressing the human cytokines interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) has been generated with the aim of making a model system allowing the in vivo proliferation of human hematopoietic cells. Using TG-SCID mice expressing high levels (30-35 ...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1600-0609.1998.tb01067.x
更新日期:1998-08-01 00:00:00
abstract::The development of an unusual case of primary pleural effusion in a 90-year-old human immunodeficiency virus (HIV)-negative Japanese woman with no identifiable tumor mass has been described. Pleural effusion specimens contained large diffuse lymphoma cells, with the phenotype and genotype of a B-cell lineage (positive...
journal_title:European journal of haematology
pub_type: 杂志文章
doi:10.1034/j.1600-0609.2003.00083.x
更新日期:2003-07-01 00:00:00