Abstract:
:BCL2 is deregulated in diffuse large B-cell lymphoma (DLBCL) by the t(14;18) translocation, gene amplification and/or nuclear factor-κB signaling. RNA-seq data have recently shown that BCL2 is the most highly mutated gene in germinal center B-cell (GCB) DLBCL. We have sequenced BCL2 in 298 primary DLBCL biopsies, 131 additional non-Hodgkin lymphoma biopsies, 24 DLBCL cell lines and 51 germline DNAs. We found frequent BCL2 mutations in follicular lymphoma (FL) and GCB DLBCL, but low levels of BCL2 mutations in activated B-cell DLBCL, mantle cell lymphoma, small lymphocytic leukemia and peripheral T-cell lymphoma. We found no BCL2 mutations in GC centroblasts. Many mutations were non-synonymous; they were preferentially located in the flexible loop domain, with few in BCL2-homology domains. An elevated transition/transversions ratio supports that the mutations result from somatic hypermutation. BCL2 translocations correlate with, and are likely important in acquisition of, additional BCL2 mutations in GCB DLBCL and FL. DLBCL mutations were not independently associated with survival. Although previous studies of BCL2 mutations in FL have reported mutations to result in pseudo-negative BCL2 protein expression, we find this rare in de-novo DLBCL.
journal_name
Leukemiajournal_title
Leukemiaauthors
Schuetz JM,Johnson NA,Morin RD,Scott DW,Tan K,Ben-Nierah S,Boyle M,Slack GW,Marra MA,Connors JM,Brooks-Wilson AR,Gascoyne RDdoi
10.1038/leu.2011.378subject
Has Abstractpub_date
2012-06-01 00:00:00pages
1383-90issue
6eissn
0887-6924issn
1476-5551pii
leu2011378journal_volume
26pub_type
杂志文章相关文献
LEUKEMIA文献大全abstract::RT-PCR assays used to detect acute promyelocytic leukemia (APL) are generally considered less sensitive than those for other hematological malignancies, such as CGL. Most patients with APL express del(17q)-derived RAR alpha-PML transcripts as well as the putative leukemogenic PML-RAR alpha associated with add(15q). We...
journal_title:Leukemia
pub_type: 临床试验,杂志文章
doi:
更新日期:1996-01-01 00:00:00
abstract::An unambiguous case of Sèzary syndrome associated with the presence of unusual retroviral infection markers is described. The blood smear showed 15% typical Sèzary cells but also rare atypical lymphocytes with convoluted nuclei, evocative of characteristic adult T-cell leukemia (ATL) flower cells. However, the patient...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1994-01-01 00:00:00
abstract::The three DNA methyltransferase (DNMT)-inhibiting cytosine nucleoside analogues, azacitidine, decitabine and zebularine, which are currently studied as nonintensive therapy for myelodysplastic syndromes and acute myeloid leukemia (AML), differ in structure and metabolism, suggesting that they may have differential mol...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2008.397
更新日期:2009-06-01 00:00:00
abstract::Highly polymorphic tandemly repetitive DNA sequences provide powerful genetic markers for the identification of individuals by restriction fragment length polymorphisms (RFLP) even in close relatives. Over a three-year period, 61 consecutive patients from a single institution undergoing allogeneic bone marrow transpla...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1993-05-01 00:00:00
abstract::Autoradiographic analysis of the binding of radiolabeled murine IL-6 to murine cells revealed that blast cells, megakaryocytic and monocytic cells in the marrow expressed receptors but not erythroid, eosinophilic or neutrophilic granulocytic cells. In the thymus, spleen and lymph nodes, most cells expressing receptors...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1994-10-01 00:00:00
abstract::Different normal and malignant human B-cell populations were studied with a twofold aim: to define which cytokines are produced in vivo, and to assess the relationship between cytokine production and kinetic state. To analyse normal B-cells representative of different stages of activation and proliferation in vivo, we...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1992-02-01 00:00:00
abstract::Leukemia-specific promoters and enhancers for gene therapy had never been reported. Since the Wilms' tumor gene WT1 is overexpressed in almost all types of leukemia, WT1 is an ideal target of leukemia-specific therapy. To explore the possibility of gene therapy for leukemia using WT1 promoter and enhancer, their activ...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2403260
更新日期:2004-03-01 00:00:00
abstract::The presence of rare malignant stem cells supplying a hierarchy of malignant cells has recently been reported. In human acute myelogenous leukemia (AML), the leukemia stem cells (LSCs) have been phenotypically restricted within the CD34+CD38- fraction. To understand the origin of malignant cells in primary human B-pre...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2008.83
更新日期:2008-06-01 00:00:00
abstract::In this report, a Radiation leukemia virus-transformed murine T cell lymphoma is described which is dependent on the interleukin-2 (IL-2) growth factor for proliferation under single cell conditions of growth. It was isolated from a C57BL mouse which had been primed with the Radiation leukemia virus-induced thymoma, C...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1988-02-01 00:00:00
abstract::We present the long-term results of three consecutive clinical trials (Total Therapy studies 11, 12 and 13A) conducted for children with newly diagnosed acute lymphoblastic leukemia (ALL) between 1984 and 1994. In study 11 (1984-1988), the overall event-free survival rates (+/-1 s.e.) were 71.8 +/- 2.4% and 69.3 +/- 2...
journal_title:Leukemia
pub_type: 杂志文章,meta分析
doi:10.1038/sj.leu.2401938
更新日期:2000-12-01 00:00:00
abstract::The discovery of almost identical or 'stereotyped' B-cell receptor immunoglobulins (BcR IG) among unrelated patients with chronic lymphocytic leukemia (CLL) cemented the idea of antigen selection in disease ontogeny and evolution. The systematic analysis of the stereotypy phenomenon in CLL revealed that around one-thi...
journal_title:Leukemia
pub_type: 杂志文章,评审
doi:10.1038/leu.2016.322
更新日期:2017-02-01 00:00:00
abstract::We have investigated the effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and several potent vitamin D3 analogs [1,25(OH)2-16-ene-23-yne-D3; 1,25(OH)2-16-ene-23-yne-26,27-F6-D3] on productive infection by human immunodeficiency virus (HIV) in human macrophages. Macrophages derived from the peripheral blood were eithe...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1993-10-01 00:00:00
abstract::Synergistic molecular vulnerabilities enhancing hypomethylating agents in myeloid malignancies have remained elusive. RNA-interference drug modifier screens identified antiapoptotic BCL-2 family members as potent 5-Azacytidine-sensitizing targets. In further dissecting BCL-XL, BCL-2 and MCL-1 contribution to 5-Azacyti...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2014.44
更新日期:2014-08-01 00:00:00
abstract::P38α/β has been described as a tumor-suppressor controlling cell cycle checkpoints and senescence in epithelial malignancies. However, p38α/β also regulates other cellular processes. Here, we describe a role of p38α/β as a regulator of acute lymphoblastic leukemia (ALL) proliferation and survival in experimental ALL m...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2015.153
更新日期:2015-12-01 00:00:00
abstract::Long-term disease-free survival following conventional cytotoxic therapy is extremely rare in patients with advanced-stage mantle cell lymphoma (MCL). High-dose conditioning therapy consisting of hyperfractionated total body irradiation (TBI, 14.4 Gy) and cyclophosphamide (200 mg/kg) was therefore offered to 13 patien...
journal_title:Leukemia
pub_type: 临床试验,杂志文章
doi:
更新日期:1996-12-01 00:00:00
abstract::It has been suggested that abnormalities of chromosome 3 at bands q21 and q26 are associated with the presence of increased numbers of abnormal megakaryocytes in patients with hematologic malignancies. The pretreatment bone marrows of 287 patients with leukemia (acute myeloid leukemia (AML), 225 patients; acute lympho...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1990-05-01 00:00:00
abstract::A poorly defined transforming event(s) affects the pluripotential bone marrow (BM) stem cell in myelodysplastic syndromes (MDS), conferring a growth advantage upon it which leads eventually to monoclonal hematopoiesis. The progeny of this transformed ancestor undergo recognizable albeit dysplastic maturation. We propo...
journal_title:Leukemia
pub_type: 杂志文章,评审
doi:
更新日期:1996-10-01 00:00:00
abstract::In this study, the abilities of constitutive and conditional forms of the three Raf kinases to abrogate the cytokine dependency of FDC-P1 cells were examined. The constitutively active forms (delta) of all three Raf kinases were fused to the hormone-binding domain of the estrogen receptor (ER), rendering their activit...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2401720
更新日期:2000-04-01 00:00:00
abstract::Imatinib is a highly effective therapy for chronic phase-chronic myeloid leukaemia (CP-CML) patients; however, responses to frontline imatinib are variable. The human organic cation transporter 1 (OCT1; SLC22A1) has been reported to be the main influx transporter involved in imatinib uptake into CML cells. Furthermore...
journal_title:Leukemia
pub_type: 杂志文章,评审
doi:10.1038/leu.2015.170
更新日期:2015-10-01 00:00:00
abstract::There is abundant evidence that leukemia arise through somatically acquired genetic changes. Familial or congenital predisposition is rarely involved. These genetic changes are often visible as chromosomal aberrations. Molecular analyses of the DNA sequences rearranged in leukemia has demonstrated the presence of cell...
journal_title:Leukemia
pub_type: 杂志文章,评审
doi:
更新日期:1992-11-01 00:00:00
abstract::ATP-binding-cassette (ABC) transporters are evolutionary extremely well-conserved transmembrane proteins that are highly expressed in hematopoietic stem cells (HSCs). The physiological function in human stem cells is believed to be protection against genetic damage caused by both environmental and naturally occurring ...
journal_title:Leukemia
pub_type: 杂志文章,评审
doi:10.1038/sj.leu.2404859
更新日期:2007-10-01 00:00:00
abstract::The efficacy of antibody-based immunotherapy is due to the activation of apoptosis, the engagement of antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity (CDC). We developed a novel strategy to enhance CDC using bispecific antibodies (bsAbs) that neutralize the C-regulators CD55 and CD59 to ...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2014.185
更新日期:2015-02-01 00:00:00
abstract::The human factor-dependent leukemia cell line UCSD/AML1 contains the t(3;3) (q21;q26) characteristic of the syndrome of acute leukemia with high platelets. The human homologue of the murine leukemia oncogene evi-1 was recently localized to chromosome 3q24-3q28 and transcription of evi-1 is a frequent event in mouse-re...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1992-05-01 00:00:00
abstract::A relationship was proved between constitutive activity of leukemic cell c-jun-N-terminal kinase (JNK) and treatment failure in AML. Specifically, early treatment failure was predicted by the presence of constitutive JNK activity. The mechanistic origins of this association was sought. A multidrug resistant leukemic c...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2402457
更新日期:2002-05-01 00:00:00
abstract::Adults with acute lymphoblastic leukemia (ALL) do worse than children. From 7/2008 to 12/2014, Nordic and Baltic centers treated 1509 consecutive patients aged 1-45 years with Philadelphia chromosome-negative ALL according to the NOPHO ALL2008 without cranial irradiation. Overall, 1022 patients were of age 1-9 years (...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2017.265
更新日期:2018-03-01 00:00:00
abstract::The oncogene kit has been shown genetically to map in the W locus of the mouse. This locus is known to have an important role in the regulation of normal hemopoietic stem cell growth. The blast cells of acute myeloblastic leukemia may be considered to arise in predeterministic stem cells. Accordingly, we sought eviden...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1989-10-01 00:00:00
abstract::Chromosomal rearrangements of the human MLL/KMT2A gene are associated with infant, pediatric, adult and therapy-induced acute leukemias. Here we present the data obtained from 2345 acute leukemia patients. Genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and 1...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2017.213
更新日期:2018-02-01 00:00:00
abstract::We report the results of a phase I dose escalation trial of the multikinase inhibitor sorafenib in relapsed and refractory acute leukemia patients using an intermittent dosing regimen. Fifteen patients with advanced leukemia (12 with acute myeloid leukemia, 2 with acute lymphoblastic leukemia, 1 with biphenotypic) and...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2010.132
更新日期:2010-08-01 00:00:00
abstract::We performed cytogenetic and molecular analysis of the BCR-ABL rearrangement by polymerase chain reaction (PCR) in 39 consecutive cases of adult acute lymphoblastic leukemia (ALL). Eleven patients had a Philadelphia (Ph) chromosome. Thirteen patients had a BCR-ABL rearrangement, involving minor breakpoint cluster regi...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1993-07-01 00:00:00
abstract::Since graft-versus-leukemia (GVL) is the main weapon for disease eradication after reduced intensity conditioning (RIC) allogeneic SCT, the availability of sensitive and specific techniques to monitor changes in tumor load after transplant are especially helpful. These minimal residual disease techniques would allow a...
journal_title:Leukemia
pub_type: 杂志文章,评审
doi:10.1038/sj.leu.2402550
更新日期:2002-08-01 00:00:00