Abstract:
BACKGROUND:The nucleoside analogue fludarabine is used in the treatment of chronic lymphocytic leukemia. It triggers p53-mediated apoptosis, although the mutational status of p53 does not fully account for heterogeneity in responsiveness to treatment. The aim of this study was to identify new genes implicated in fludarabine action as well as to determine the role of equilibrative nucleoside transporters (ENT) in the transcriptomic response triggered by this drug in chronic lymphocytic leukemia cells bearing wild type p53. DESIGN AND METHODS:We performed gene expression profiling in cells from two fludarabine-sensitive and two fludarabine-resistant cases of chronic lymphocytic leukemia treated with fludarabine either in the presence or the absence of nitrobenzylthioinosine, a hENT1-specific blocker. Twenty selected fludarabine-inducible genes were validated using Taqman low-density arrays in cells from 20 chronic lymphocytic leukemia patients with the same experimental design. RESULTS:Sixteen of the twenty genes (DDB2, GADD45A, TYMS, BAX, TIGAR, FAS, TNFSF7, TNFSF9, CCNG1, CDKN1A, MDM2, SESN1, MAP4K4, PPM1D, OSBPL3 and WIG1) correlated with the ex vivo sensitivity of chronic lymphocytic leukemia cells to fludarabine, TIGAR (TP53-induced glycolysis and apoptosis regulator) being the gene that showed the strongest correlation (p<0.0001; r2= 0.6022).We observed that the transcriptomic response was weakly sensitive to the hENT1 blocker nitrobenzylthioinosine. Interestingly, we also found a correlation between hENT2 expression and induction of TIGAR after fludarabine treatment. CONCLUSIONS:We demonstrate a correlation between the recently described p53-inducible apoptosis gene TIGAR and both sensitivity to fludarabine and hENT2 expression in chronic lymphocytic leukemia cells. These results, as well as the variability in fludarabine response among chronic lymphocytic leukemia patients with wild type p53, support the major role of hENT2 in the uptake of fludarabine into chronic lymphocytic leukemia cells.
journal_name
Haematologicajournal_title
Haematologicaauthors
López-Guerra M,Trigueros-Motos L,Molina-Arcas M,Villamor N,Casado FJ,Montserrat E,Campo E,Colomer D,Pastor-Anglada Mdoi
10.3324/haematol.13186subject
Has Abstractpub_date
2008-12-01 00:00:00pages
1843-51issue
12eissn
0390-6078issn
1592-8721pii
haematol.13186journal_volume
93pub_type
杂志文章相关文献
HAEMATOLOGICA文献大全abstract::Homeobox containing transcription factors are frequently deregulated in human hematologic malignant diseases either indirectly through an abnormality of an upstream factor, or directly through rearrangement of the gene itself. Study of T-cell acute lymphoblastic leukemia identified the related non-clustered homeobox t...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.12595
更新日期:2008-07-01 00:00:00
abstract::Forty-six patients with chronic myeloid leukemia receiving imatinib mesylate (39 in chronic phase, one in accelerated phase, and six in blastic crisis), were studied for a 20-62 month follow-up period by cytogenetics and fluorescence in situ hybridization using dual-color, dual-fusion BCR and ABL probes. This approach...
journal_title:Haematologica
pub_type: 信件
doi:
更新日期:2006-07-01 00:00:00
abstract::In the GIMEMA LAL 0904 protocol, adult Philadelphia positive acute lymphoblastic leukemia patients were treated with chemotherapy for induction and consolidation, followed by maintenance with imatinib. The protocol was subsequently amended and imatinib was incorporated in the induction and post-remission phase togethe...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2016.144535
更新日期:2016-12-01 00:00:00
abstract::We quantified Wilm's tumor gene (WT1) using a real time quantitative polymerase chain reaction in 20 adult patients with acute lymphoblastic leukemia at presentation. A WT1 level greater than 906 (median value for the whole series) was a significant predictor of a poor disease-free and overall survival in uni- and mul...
journal_title:Haematologica
pub_type: 信件
doi:
更新日期:2006-02-01 00:00:00
abstract:BACKGROUND:Treatment of older patients with non-Hodgkin's lymphoma (NHL) is difficult and conflicting. Lower responsiveness to therapy has been reported; however, the high risk of treatment morbidity, drug-dose reduction, and the occurrence of unrelated deaths might account for the poor outcome of NHL in the elderly. ...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:1991-05-01 00:00:00
abstract::Immune dysregulation is a mechanism contributing to ineffective hematopoiesis in a subset of myelodysplastic syndrome patients. We report the first US multicenter non-randomized, phase II trial examining the efficacy of rabbit(r)-anti-thymocyte globulin using 2.5 mg/kg/day administered daily for 4 doses. The primary e...
journal_title:Haematologica
pub_type: 杂志文章,多中心研究
doi:10.3324/haematol.2012.083345
更新日期:2014-07-01 00:00:00
abstract::CLLU1, located at chromosome 12q22, encodes a transcript specific to chronic lymphocytic leukemia and has potential prognostic value. We assessed the value of CLLU1 expression in the LRF CLL4 randomized trial. Samples from 515 patients with chronic lymphocytic leukemia were collected immediately before the start of tr...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2012.070201
更新日期:2013-02-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human metabolic disorder in southern China. We investigated the incidence and distribution of mutations, the molecular pathology of affected females and the haplotype association with G6PD deficiency in patients from the Gu...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:2006-10-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:How to reach the correct diagnosis of a lymph node enlargement is still a problem which strongly challenges the knowledge and experience of the clinician. Organized and specifically oriented literature on the right sequential steps and the logical criteria that should guide this diagnostic appr...
journal_title:Haematologica
pub_type: 杂志文章,评审
doi:
更新日期:1999-03-01 00:00:00
abstract::Anemia is highly prevalent, especially in older individuals. In selected populations, anemia has been reported to be associated with impaired survival and health-related quality of life. However, data on this impact in the general population are rare. Furthermore, discussions on the optimal definition of anemia have n...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2018.195552
更新日期:2019-03-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Improvements in the management of childhood acute lymphoblastic leukemia (ALL) did not prevent 20% to 30% of patients suffering from relapse. Moreover, the probability of relapse can rise up to 50% for some children presenting with very high risk (VHR) factors. Intensive chemotherapy and espec...
journal_title:Haematologica
pub_type: 杂志文章,评审
doi:
更新日期:2002-08-01 00:00:00
abstract::Interactions between chronic lymphocytic leukemia (CLL) B cells and the bone marrow (BM) microenvironment play a major function in the physiopathology of CLL. Extracellular vesicles (EVs), which are composed of exosomes and microparticles, play an important role in cell communication. However, little is known about th...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2016.163337
更新日期:2017-09-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Aberrant promoter methylation targets CpG islands causing gene silencing. We explored aberrant promoter methylation of genes potentially involved in B-cell malignancies and encoding proteins implicated in DNA repair (O6-methylguanine-DNA methyltransferase, MGMT), detoxification of environmenta...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:2004-02-01 00:00:00
abstract:BACKGROUND:Antithymocyte globulin or human Jurkat T-cell-line-derived antilymphocyte globulin is used in allogeneic stem cell transplantation to induce in vivo T-cell depletion to facilitate engraftment and lower graft-versus-host disease. In vitro studies suggest that antithymocyte globulin, besides causing T-cell dep...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.12665
更新日期:2008-09-01 00:00:00
abstract::A case of Di Guglielmo's syndrome passed through the three stages of chronic erythromyelosis, erythroleukemia and acute myeloid leukemia (AML). According to the FAB classification the subsequent stages of this syndrome were refractory anemia (RA), RA with excess of blasts (RAEB), AML-M6, AML-M2 and undifferentiated AM...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:1997-07-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Aggressive diffuse large cell non-Hodgkin's lymphoma (DLCL) occurring late after a solid organ transplant fails to regress after discontinuation of immunosuppression. Moreover, chemotherapy treatment is associated with a high mortality rate due to severe toxicity. Since the majority of post-tr...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:2001-06-01 00:00:00
abstract::Some prospective studies showed that rabbit antithymocyte globulin was inferior to horse antithymocyte globulin as first-line therapy for patients with severe aplastic anemia. We retrospectively analyzed the clinical outcome of 455 children with severe aplastic anemia who received horse antithymocyte globulin (n=297) ...
journal_title:Haematologica
pub_type: 杂志文章,多中心研究
doi:10.3324/haematol.2013.089268
更新日期:2014-04-01 00:00:00
abstract::Double umbilical cord blood transplantation is increasingly applied in the treatment of adult patients with high-risk hematological malignancies and has been associated with improved engraftment as compared to that provided by single unit cord blood transplantation. The mechanism of improved engraftment is, however, s...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2014.106690
更新日期:2014-11-01 00:00:00
abstract::It is currently unknown whether immunosuppressive therapy or hematopoietic stem cell transplantation is the most appropriate treatment strategy for children with refractory cytopenia and normal karyotype or trisomy 8. We report on 31 children with hypoplastic refractory cytopenia treated with immunosuppressive therapy...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.10683
更新日期:2007-03-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:The efficacy and safety of added dexamethasone were assessed in patients with relapsed and/or refractory multiple myeloma who had a suboptimal response to bortezomib alone. DESIGN AND METHODS:In two previously reported, open-label, multicenter phase 2 studies, bortezomib 1.0 or 1.3 mg/m2 was ...
journal_title:Haematologica
pub_type: 杂志文章,多中心研究,随机对照试验
doi:
更新日期:2006-07-01 00:00:00
abstract::Effects of concurrent inhibition of mTORC1/2 and Bcl-2/Bcl-xL in human acute myeloid leukemia cells were examined. Tetracycline-inducible Bcl-2/Bcl-xL dual knockdown markedly sensitized acute myeloid leukemia cells to the dual TORC1/2 inhibitor INK128 in vitro as well as in vivo. Moreover, INK128 co-administered with ...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2015.130351
更新日期:2015-12-01 00:00:00
abstract:BACKGROUND:Impaired regulation of hepcidin in response to iron is the cause of genetic hemochromatosis associated with defects of HFE and transferrin receptor 2. However, the role of these proteins in the regulation of hepcidin expression is unclear. DESIGN AND METHODS:Hepcidin expression, SMAD and extracellular signa...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2010.027003
更新日期:2010-11-01 00:00:00
abstract::Plasma levels of several soluble factors were assayed in 31 untreated patients with high-grade non-Hodgkin's lymphomas (NHL). The results showed statistically significant higher average levels of interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-2 receptor (IL-2r) and transferrin receptor (...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:1992-11-01 00:00:00
abstract::This study investigated the kinetics of CD3+-T cell chimerism (TCC) in 102 patients receiving reduced intensity conditioning allogeneic stem cell transplantation (RIC-allo-SCT) from an HLA-identical sibling. Patients with full donor TCC at day 30 had a higher incidence of grade 2-4 acute GVHD compared to patients in m...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.10971
更新日期:2007-07-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Hepatitis C virus (HCV) infection is an important cause of morbidity and mortality in patients affected by hereditary bleeding disorders and treated with non-virus inactivated clotting factor concentrates during the 1970s. INFORMATION SOURCES:In this review, we briefly report the present know...
journal_title:Haematologica
pub_type: 杂志文章,评审
doi:
更新日期:2002-05-01 00:00:00
abstract::The causes of myeloproliferative neoplasm (MPN) are unknown. We conducted a large population-based study including 11,039 myeloproliferative neoplasm patients and 43,550 matched controls with the aim of assessing the associations between a personal history of a broad span of autoimmune diseases and subsequent risk of ...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2009.020412
更新日期:2010-07-01 00:00:00
abstract::Transient pancytopenia preceding childhood acute lymphoblastic leukemia (ALL) is an unfrequent but well-known event. The association of this preleukemic syndrome with hepatitis is extremely rare, with only two such cases having been published in the literature. We report the case of a 16-year-old boy who was diagnosed...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:1998-06-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Acquired red cell aplasia (RCA) is a rare disorder and can be either idiopathic or associated with certain diseases, pregnancy, or drugs. In exceptionally rare cases, it has been reported to co-exist with other autoimmune cytopenias. We report a high incidence of RCA and autoimmune hemolytic a...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.10733
更新日期:2007-08-01 00:00:00
abstract::HTLV-1 infections and their associated diseases are very rare in Italy, as well as in most parts of Europe, occurring prevalently in subjects related to endemic areas. The HTLV-1-associated leukemia/lymphoma, ATLL, is a very aggressive T-cell non-Hodgkin's lymphoma which can be difficult to recognize in non-endemic ar...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:2003-07-01 00:00:00
abstract::In the European Intergroup EURO-LB02 trial, children and adolescents with lymphoblastic lymphoma underwent the non-Hodgkin lymphoma Berlin-Frankfurt-Münster protocol without prophylactic cranial radiotherapy. The primary aims of this trial were to test whether replacing prednisone with dexamethasone during induction i...
journal_title:Haematologica
pub_type: 临床试验,杂志文章
doi:10.3324/haematol.2015.139162
更新日期:2017-12-01 00:00:00