Abstract:
:Ikaros plays an important role in the control of differentiation and proliferation of all lymphoid lineages. The expression of short isoforms lacking DNA-binding motifs alters the differentiation capacities of hematopoietic progenitors, arresting lineage commitment. We sought to determine whether molecular abnormalities involving the IKZF1 gene were associated with resistance to tyrosine kinase inhibitors (TKIs) in Ph+ acute lymphoblastic leukemia (ALL) patients. Using reverse-transcribed polymerase chain reaction, cloning, and nucleotide sequencing, only the non-DNA-binding Ik6 isoform was detected in 49% of Ph+ ALL patients. Ik6 was predominantly localized to the cytoplasm versus DNA-binding Ik1 or Ik2 isoforms, which showed nuclear localization. There was a strong correlation between nonfunctional Ikaros isoforms and BCR-ABL transcript level. Furthermore, patient-derived leukemia cells expressed oncogenic Ikaros isoforms before TKI treatment, but not during response to TKIs, and predominantly at the time of relapse. In vitro overexpression of Ik6 strongly increased DNA synthesis and inhibited apoptosis in TKI-sensitive cells. Genomic sequence and computational analyses of exon splice junction regions of IKZF1 in Ph+ ALL patients predicted several mutations that may alter alternative splicing. These results establish a previously unknown link between specific molecular defects that involve alternative splicing of the IKZF1 gene and the resistance to TKIs in Ph+ ALL patients.
journal_name
Bloodjournal_title
Bloodauthors
Iacobucci I,Lonetti A,Messa F,Cilloni D,Arruga F,Ottaviani E,Paolini S,Papayannidis C,Piccaluga PP,Giannoulia P,Soverini S,Amabile M,Poerio A,Saglio G,Pane F,Berton G,Baruzzi A,Vitale A,Chiaretti S,Perini G,Foà Rdoi
10.1182/blood-2007-09-112631subject
Has Abstractpub_date
2008-11-01 00:00:00pages
3847-55issue
9eissn
0006-4971issn
1528-0020pii
blood-2007-09-112631journal_volume
112pub_type
杂志文章相关文献
BLOOD文献大全abstract::Bcr-abl fusion peptide-specific CD4+ T-lymphocyte clones have recently been shown to augment colony formation by chronic myelogenous leukemia (CML) cells in a bcr-abl type-specific and HLA class II-restricted manner without addition of exogenous antigen. These findings suggest that CML cells can naturally process and ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v98.5.1498
更新日期:2001-09-01 00:00:00
abstract::The human CD34 surface antigen is selectively expressed on stem/progenitor cells within the hematopoietic system. Because CD34 expression is tightly linked to the immature status of hematopoietic cells, with expression being rapidly lost as hematopoietic cells mature and differentiate, an examination of its regulation...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1994-04-01 00:00:00
abstract::Between 1990 and 1996, we conducted a randomized trial in adults with newly diagnosed acute myeloid leukemia (AML) in order to compare relapse-free interval (RFI) after double induction (arm B), timed-sequential induction (arm C), or control "3 + 7" induction (arm A). Patients achieving complete remission (CR) after i...
journal_title:Blood
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1182/blood-2003-10-3561
更新日期:2004-10-15 00:00:00
abstract::Congenital dyserythropoietic anemias (CDAs) are a heterogeneous group of inherited anemias that affect the normal differentiation-proliferation pathways of the erythroid lineage. They belong to the wide group of ineffective erythropoiesis conditions that mainly result in monolinear cytopenia. CDAs are classified into ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.2019000948
更新日期:2020-09-10 00:00:00
abstract::Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the most effective tumor immunotherapy available. Although allo-HSCT provides beneficial graft-versus-tumor effects, acute GVHD (aGVHD) is the primary source of morbidity and mortality after HSCT. Diagnosis of aGVHD is typically based on clinical sympto...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2012-08-355990
更新日期:2013-01-24 00:00:00
abstract::The cellular and molecular events underlying the formation and differentiation of mesoderm to derivatives such as blood are critical to our understanding of the development and function of many tissues and organ systems. How different mesodermal populations are set aside to form specific lineages is not well understoo...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2005-10-4120
更新日期:2006-04-15 00:00:00
abstract::Until recently, IgE-activated mast cells have been regarded merely as effector cells of adaptive immune responses, involved in allergic reactions and mucosal immunity to parasites. Herein, we report that murine dermal mast cells, activated by local administration of a cream containing the synthetic TLR7 ligand imiquim...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2006-07-036889
更新日期:2007-08-01 00:00:00
abstract::Cytotoxic T lymphocytes kill target cells via the polarized secretion of cytotoxic granules at the immune synapse. The lytic granules are initially recruited around the polarized microtubule-organizing center. In a dynein-dependent transport process, the granules move along microtubules toward the microtubule-organizi...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-09-382556
更新日期:2012-04-26 00:00:00
abstract::miRNAs have emerged as master regulators of cancer-related events. miRNA dysregulation also occurs in Kaposi sarcoma (KS). Exploring the roles of KS-associated miRNAs should help to identify novel angiogenesis and lymphangiogenesis pathways. In the present study, we show that Kaposi sarcoma-associated herpesvirus (KSH...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-01-330589
更新日期:2011-09-08 00:00:00
abstract::Platelet-associated C3 (PA-C3) was measured with a quantitative immunofluorescence assay. With this assay, PA-C3 levels were determined for 78 normal volunteers, 30 patients with immune thrombocytopenic purpura (ITP), and 20 patients with nonimmune thrombocytopenias. Platelet-associated IgG (PA-IgG) levels were also m...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1982-05-01 00:00:00
abstract::Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma in the Western world. FL cell-intrinsic and cell-extrinsic factors influence FL biology and clinical outcome. To further our understanding of the genetic basis of FL, we performed whole-exome sequencing of 23 highly purified FL cases and 1 transfo...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2014-06-582650
更新日期:2015-01-22 00:00:00
abstract::Although the role of systemic activation of the nuclear factor kappaB (NF-kappaB) pathway in septic coagulation has been well documented, little is known about the contribution of endothelial-specific NF-kappaB signaling in this pathologic process. Here, we used transgenic mice that conditionally overexpress a mutant ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-02-205914
更新日期:2009-09-17 00:00:00
abstract::The response of sickle cells with varying water content to alterations in oxygen tension has been studied. Cells that were severely dehydrated while sickled retained the characteristic sickled morphology even after prolonged reoxygenation. When the cell water content was increased by reduction of the suspending medium...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1980-05-01 00:00:00
abstract::Stem cell localization, conservation, and differentiation is believed to occur in niches in the marrow stromal microenvironment. Our recent observation that long-term in vitro human hematopoiesis requires a stromal heparan sulfate proteoglycan (HSPG) led us to hypothesize that such HSPG may orchestrate the formation o...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1998-12-15 00:00:00
abstract::Immune function has been restored in 9 of 10 children with X-linked severe combined immunodeficiency by gamma c gene transfer in CD34+ cells. The distribution of both T-cell receptor (TCR) V beta family usage and TCR V beta complementarity-determining region 3 (CDR3) length revealed a broadly diversified T-cell repert...
journal_title:Blood
pub_type: 临床试验,杂志文章
doi:10.1182/blood-2004-07-2648
更新日期:2005-04-01 00:00:00
abstract::Transplantation of ex vivo expanded human umbilical cord blood cells (hCB) only partially enhances the hematopoietic recovery after myelosuppressive therapy. Incubation of hCB with optimal combinations of cytokines and niche cells, such as endothelial cells (ECs), could augment the efficiency of hCB expansion. We have...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-12-398115
更新日期:2012-08-09 00:00:00
abstract::In lymphatic tissues, chronic lymphocytic leukemia (CLL) cells are interspersed with CD68(+) nurselike cells (NLCs), T cells, and other stromal cells that constitute the leukemia microenvironment. However, the mechanism regulating colocalization of CLL and these accessory cells are largely unknown. To dissect the mole...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2008-07-170415
更新日期:2009-03-26 00:00:00
abstract::Cord blood (CB) is used increasingly as a source of hematopoietic stem cells because of a lower risk of acute and chronic graft-versus-host disease (GVHD). However, there is some concern regarding the ability to adequately reconstitute host immune response due to the immaturity and naivety of CB T cells. This study wa...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v99.4.1458
更新日期:2002-02-15 00:00:00
abstract::Immunosuppression resulting in impaired Epstein-Barr virus (EBV)-specific T-cell immunity is involved in the pathogenesis of EBV-positive post-transplantation lymphoproliferative disorder (EBV(+) PTLD). Restoration of EBV-specific T-cell immunity by adoptive immunotherapy can induce remission. EBV-nuclear antigen-1 (E...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-03-274076
更新日期:2010-09-30 00:00:00
abstract::Human bone marrow (BM) cells contain low levels of the DNA repair protein, O6-alkylguanine-DNA alkyltransferase, which may explain their susceptibility to nitrosourea-induced cytotoxicity and the development of secondary leukemia after nitrosourea treatment. Isolated CD34+ myeloid progenitors were also found to have l...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1996-09-01 00:00:00
abstract::The median age of chronic myeloid leukemia (CML) patients is ~60 years, and age is still considered an important prognostic factor, included in Sokal and EURO risk scores. However, few data are available about the long-term outcome of older patients treated with imatinib (IM) frontline. We analyzed the relationship be...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-12-324228
更新日期:2011-05-26 00:00:00
abstract::Ubiquitin is suggested to play a key role in essential intracellular functions, such as heat shock response, protein breakdown, and regulation of immune responses. Ubiquitin has also been detected in the extracellular space, but the function and biologic significance is unclear. We describe a new function of extracell...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-03-0918
更新日期:2003-03-01 00:00:00
abstract::The inv(11)(p15q22) is a recurrent chromosomal abnormality associated with de novo and therapy-related myeloid malignancies. Here we report the molecular definition of this chromosomal aberration in four patients. Positional cloning showed the consistent rearrangement of the DDX10 gene on chromosome 11q22, which encod...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1997-06-01 00:00:00
abstract::It has been suggested that human cytomegalovirus (HCMV) evades the immune system by infecting and paralyzing antigen-presenting cells. This view is based mainly on studies of dendritic cells (DCs) obtained after culture of monocytes (moDCs). It is contradicted by the asymptomatic course of HCMV infection in healthy pe...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2005-05-2016
更新日期:2006-03-01 00:00:00
abstract::A novel thrombin inhibitor based on single-stranded (ss) deoxynucleotides with the sequence GGTTGGTGTGGTTGG (thrombin aptamer) has been recently discovered. In this study, we tested its efficacy in inhibiting clot-bound thrombin activity and platelet thrombus formation in an ex vivo whole artery angioplasty model. The...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1994-02-01 00:00:00
abstract::In this study, we examined in detail the interaction of platelet factor-4 (PF-4) with fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF) and the effect of PF-4-derived synthetic peptides. We show that a peptide between amino acids 47 and 70 that contains the heparin-binding lysine-rich si...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1999-08-01 00:00:00
abstract::Merkel cell polyomavirus (MCPyV), a DNA tumor virus, has been found to be associated with Merkel cell carcinoma and chronic lymphocytic leukemia. MCPyV sequences have also been detected in various normal tissues in tumor-affected patients. Immunologic studies have detected MCPyV antibodies in as many as 80% of healthy...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-09-310557
更新日期:2011-06-30 00:00:00
abstract::Posttranslational protein modifications (PTMs) are necessary for cells to function properly. The role of PTMs in regulating immune responses, specifically those mediated by dendritic cells (DCs), which are critical for both innate and adaptive immunity, is not well understood. Utilizing multiple but complementary appr...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2013-02-486373
更新日期:2013-09-19 00:00:00
abstract::Atypical hemolytic uremic syndrome (aHUS) is associated with complement system dysregulation, and more than 25% of pediatric aHUS cases are linked to mutations in complement factor H (CFH) or CFH autoantibodies. The observation of thrombocytopenia and platelet-rich thrombi in the glomerular microvasculature indicates ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-03-205096
更新日期:2009-11-12 00:00:00
abstract::Bruton tyrosine kinase (Btk) has a well-defined role in B-cell development, whereas its expression in osteoclasts (OCs) further suggests a role in osteoclastogenesis. Here we investigated effects of PCI-32765, an oral and selective Btk inhibitor, on osteoclastogenesis as well as on multiple myeloma (MM) growth within ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-12-396853
更新日期:2012-08-30 00:00:00