Abstract:
:The acquired kinase mutation JAK2V617F plays a central role in myeloproliferative neoplasms (MPNs). However, the mechanisms responsible for the malignant hematopoietic stem/progenitor cell (HSPC) expansion seen in patients with MPNs are not fully understood, limiting the effectiveness of current treatment. Endothelial cells (ECs) are an essential component of the hematopoietic niche, and they have been shown to express the JAK2V617F mutation in patients with MPNs. We show that the JAK2V617F-bearing vascular niche promotes the expansion of the JAK2V617F HSPCs in preference to JAK2WT HSPCs, potentially contributing to poor donor cell engraftment and disease relapse following stem cell transplantation. The expression of Chemokine (C-X-C motif) ligand 12 (CXCL12) and stem cell factor (SCF) were upregulated in JAK2V617F-bearing ECs compared to wild-type ECs, potentially accounting for this observation. We further identify that the thrombopoietin (TPO)/MPL signaling pathway is critical for the altered vascular niche function. A better understanding of how the vascular niche contributes to HSPC expansion and MPN development is essential for the design of more effective therapeutic strategies for patients with MPNs.
journal_name
Leukemiajournal_title
Leukemiaauthors
Zhan H,Lin CHS,Segal Y,Kaushansky Kdoi
10.1038/leu.2017.233subject
Has Abstractpub_date
2018-02-01 00:00:00pages
462-469issue
2eissn
0887-6924issn
1476-5551pii
leu2017233journal_volume
32pub_type
杂志文章相关文献
LEUKEMIA文献大全abstract::Imatinib (STI571, Gleevec/Glivec) is a potent selective tyrosine kinase inhibitor and is used successfully in the treatment of chronic myeloid leukemia (CML). While karyotype alterations, in addition to the Philadelphia chromosome, are a common phenomenon of progressing CML, the observation of BCR-ABL-negative leukemi...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2403861
更新日期:2005-09-01 00:00:00
abstract::The karyotypic abnormalities and clinical data on three patients in whom acute leukemia was diagnosed within the first 6 months of life are presented. The four structural chromosomal rearrangements detected in the bone marrow from these patients, i.e., t(7;12)(q36;p13) and t(1;19)(q11;q11) in case 1, t(2;10;11;12)(q21...
journal_title:Leukemia
pub_type: 杂志文章,评审
doi:
更新日期:1987-01-01 00:00:00
abstract::The stem cell leukaemia (SCL) gene is a member of the basic helix-loop-helix family of transcription factors and is essential for the development of all haematopoietic lineages. SCL is expressed in pluripotent haematopoietic stem cells and also following commitment to the erythroid, mast and megakaryocytic lineages. T...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2401420
更新日期:1999-05-01 00:00:00
abstract::Recent molecular-genetic studies have revealed that in the majority of patients with secondary leukemia induced by topoisomerase II (topo II) inhibitors and also with infantile acute leukemia (IAL), the breakpoints are clustered within scaffold attachment regions (SARs) of 3'-MLL-bcr near exon 9. Genistein, abundant i...
journal_title:Leukemia
pub_type: 社论
doi:10.1038/sj.leu.2401344
更新日期:1999-03-01 00:00:00
abstract::Homozygous deletions of the CDKN2 (MTS1/p16ink4) gene have been found at high frequency in cell lines derived from a variety of adult solid tumors. In order to investigate the status of the CDKN2 gene in cell lines established from childhood acute lymphoblastic leukemia (ALL), we surveyed 25 lines representing the maj...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1995-07-01 00:00:00
abstract::The FOXP1 (forkhead box P1) transcription factor is a marker of poor prognosis in diffuse large B-cell lymphoma (DLBCL). Here microarray analysis of FOXP1-silenced DLBCL cell lines identified differential regulation of immune response signatures and major histocompatibility complex class II (MHC II) genes as some of t...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2015.299
更新日期:2016-03-01 00:00:00
abstract::Forty of the 550 patients (7%) entered to the 11q23 Workshop had secondary (s) acute lymphoblastic leukemia (nine cases), s-acute myeloid leukemia (25 cases, predominantly of FAB type M5), s-acute leukemia unspecified (one case) or s-myelodysplastic syndrome (five cases) following treatment for a primary malignancy. B...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2401021
更新日期:1998-05-01 00:00:00
abstract::In chronic lymphocytic leukemia (CLL), stabilizing mutations of NOTCH1, affecting up to 10-15% of cases, have been associated to poor prognosis, disease progression and refractoriness to chemotherapy. NOTCH1 mutations are significantly overrepresented in trisomy 12 CLL, a disease subset frequently expressing CD49d, th...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2017.296
更新日期:2018-03-01 00:00:00
abstract::Mast cell leukemia (MCL) is a highly fatal malignancy characterized by devastating expansion of immature mast cells in various organs. Although considered a stem cell disease, little is known about MCL-propagating neoplastic stem cells. We here describe that leukemic stem cells (LSCs) in MCL reside within a CD34+/CD38...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/s41375-019-0460-6
更新日期:2019-11-01 00:00:00
abstract::Several studies involving identical twins with concordant leukemia and retrospective scrutiny of archived neonatal blood spots have shown that the TEL-AML1 fusion gene in childhood acute lymphoblastic leukemia (ALL) frequently arises before birth. A prenatal origin of childhood leukemia was further supported by the de...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2403462
更新日期:2004-10-01 00:00:00
abstract::Spliceosome mutations represent a new generation of acquired genetic alterations that affect both myeloid and lymphoid malignancies. A substantial proportion of patients with myelodysplastic syndromes (MDSs) or chronic lymphocytic leukemia (CLL) harbor such mutations, which are often missense in type. Genotype-phenoty...
journal_title:Leukemia
pub_type: 杂志文章,评审
doi:10.1038/leu.2012.86
更新日期:2012-09-01 00:00:00
abstract::This report summarizes recent findings in the field of basic and translational apoptosis research which were presented at the 1st Conference on 'Mechanisms of Cell Death and Disease: Advances in Therapeutic Intervention' organized by the European School of Hematology and the University of Texas MD Anderson Cancer Cent...
journal_title:Leukemia
pub_type: 杂志文章,评审
doi:10.1038/sj.leu.2401940
更新日期:2000-12-01 00:00:00
abstract::PCR-based monitoring of minimal residual disease (MRD) in acute leukemias can be achieved via detection of fusion gene transcripts of chromosome aberrations or detection of immunoglobulin (Ig) and T cell receptor (TCR) gene rearrangements. We wished to assess whether both PCR targets are complementary in acute myeloid...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2402387
更新日期:2002-03-01 00:00:00
abstract::The occurrence of leukemia in a gene therapy trial for SCID-X1 has highlighted insertional mutagenesis as an adverse effect. Although retroviral integration near the T-cell acute lymphoblastic leukemia (T-ALL) oncogene LIM-only protein 2 (LMO2) appears to be a common event, it is unclear why LMO2 was preferentially ta...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2404563
更新日期:2007-04-01 00:00:00
abstract::The chromosomal inversion (16)(p13q22), which is associated with the M4-eosinophilia subtype of human acute myeloid leukemia, causes the fusion of two distinct genes. The polypeptide encoded by the chimeric gene, PEBP2p/CBFp-SMMHC, retains the ability to interact with, and dominantly interfere with the function of pro...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2401821
更新日期:2000-07-01 00:00:00
abstract::Chromosomal translocations involving the MYC oncogene are a hallmark of Burkitt lymphoma but they are only found in a varying frequency in mature Burkitt-type acute lymphoblastic leukemia (B-ALL). We have investigated samples of 56 sporadic Burkitt leukemia/lymphoma patients for the translocations t(8;14)(q24;q32), t(...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2403847
更新日期:2005-08-01 00:00:00
abstract::East Asians, Asian Indians and Amerindians have a five to ten-fold lower age-adjusted incidence rate (AAIR) of chronic lymphocytic leukaemia (CLL) compared with persons of predominately European descent. The data we review suggest a genetic rather than environmental basis for this discordance. All these populations ar...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/s41375-020-01057-5
更新日期:2020-10-19 00:00:00
abstract::Cellular stressors induce various outcomes including inhibition of cell proliferation and cell death. Sodium salicylate (SA), a plant stress hormone, can suppress the proliferation or cause apoptosis in certain mammalian cancer cells. Plant stress hormones are activators of cellular responses, including cell death, to...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2402419
更新日期:2002-04-01 00:00:00
abstract::Patients with hairy cell leukemia (HCL) are prone to opportunistic infections, which suggests an impaired T-cell functioning. To investigate a possible mechanism of such an impairment, we determined the numbers of naive and memory T cells by measuring the expression of CD45R0 on CD4+ and CD8+ T cells in 23 HCL patient...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1993-01-01 00:00:00
abstract::Hematopoiesis is orchestrated by interactions between hematopoietic stem/progenitor cells (HSPCs) and stromal cells within bone marrow (BM) niches. Side population (SP) functionality is a major characteristic of HSPCs related to quiescence and resistance to drugs and environmental stresses. At steady state, SP cells a...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2013.256
更新日期:2014-04-01 00:00:00
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 ...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2011.378
更新日期:2012-06-01 00:00:00
abstract::In this study, we compared immunoglobulin heavy-chain-gene-based minimal residual disease (MRD) detection by real-time quantitative PCR (RQ-PCR) and next-generation sequencing (NGS) to assess whether NGS could overcome some limitations of RQ-PCR and further increase sensitivity, specificity, accuracy and reproducibili...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2013.375
更新日期:2014-06-01 00:00:00
abstract::Terminal blast crisis cells of chronic granulocytic leukemia are biochemically distinct. Triton-X-114 detergent phase lysates revealed that myeloid types express predominantly proteins of a 24 kd apparent molecular weight range, whereas lymphatic types do not express these molecules but a 55 kd protein band. These bio...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1988-12-01 00:00:00
abstract::To assess the efficacy and toxicity of HAA regimen (homoharritonine 4 mg/m2/day, days 1-3; cytarabine 150 mg/m2/day, days 1-7; aclarubicin 12 mg/m2/day, days 1-7) as an induction therapy in the treatment of de novo acute myeloid leukemia (AML), 48 patients with newly diagnosed AML, aged 35 (14-57) years, were entered ...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2404287
更新日期:2006-08-01 00:00:00
abstract::The immunological bone marrow (BM) microenvironment plays a major role in controlling growth and survival of clonal plasma cells (PC); this might translate into different patterns of expression of molecules involved in immune responses on PC from different types of monoclonal gammopathies (MG). We have studied the exp...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2403647
更新日期:2005-03-01 00:00:00
abstract::Current guidelines for smoldering multiple myeloma (SMM) recommend active monitoring until the onset of multiple myeloma (MM) before initiating treatment or enrollment in a clinical trial. Earlier intervention may delay progression to MM. In CENTAURUS, 123 patients with intermediate-risk or high-risk SMM were randomly...
journal_title:Leukemia
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1038/s41375-020-0718-z
更新日期:2020-07-01 00:00:00
abstract::In Philadelphia chromosome (Ph1)-positive acute lymphoblastic leukemia (ALL), some cytogenetic studies have suggested clonal derivation from a multipotential stem cell. The role of the product of the chimeric gene, P190, is not, however, well understood. We examined the expression of P190-type bcr/abl in single hemato...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1992-08-01 00:00:00
abstract::A phase III clinical trial was developed to test whether the addition of etoposide to a high-dose cytosine arabinoside regimen would improve the remission rate, duration of remission, and survival in relapsed and refractory patients with acute myelogenous leukemia. One hundred and thirty-one patients stratified by age...
journal_title:Leukemia
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:
更新日期:1994-11-01 00:00:00
abstract::By combining the polymerase chain reaction and differential library screening, a cDNA for an mRNA expressed in chicken avian myeloblastosis virus (AMV)-transformed monoblasts was isolated. This mRNA is not expressed in erythroblast or T-lymphoblast cell lines. Induced differentiation of the cells of the AMV-transforme...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1991-05-01 00:00:00
abstract::We have analysed the structure of the T-cell receptor gamma chain (TCRG) genes in a panel of biopsies taken from 24 patients with acute lymphoblastic leukemia (ALL) (13 cALL, one pre-B ALL, two null ALL and eight T-ALL) at presentation and at clinical relapse. In the majority of cases (18/24) the structure of these ge...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1994-01-01 00:00:00