Abstract:
:The role of endothelial progenitor cell (EPC)-mediated vasculogenesis in hematological malignancies is not well explored. Here, we showed that EPCs are mobilized from the bone marrow (BM) to the peripheral blood at early stages of multiple myeloma (MM); and recruited to MM cell-colonized BM niches. Using EPC-defective ID1+/- ID3-/- mice, we found that MM tumor progression is dependent on EPC trafficking. By performing RNA-sequencing studies, we confirmed that endothelial cells can enhance proliferation and favor cell-cycle progression only in MM clones that are smoldering-like and have dependency on endothelial cells for tumor growth. We further confirmed that angiogenic dependency occurs early and not late during tumor progression in MM. By using a VEGFR2 antibody with anti-vasculogenic activity, we demonstrated that early targeting of EPCs delays tumor progression, while using the same agent at late stages of tumor progression is ineffective. Thus, although there is significant angiogenesis in myeloma, the dependency of the tumor cells on EPCs and vasculogenesis may actually precede this step. Manipulating vasculogenesis at an early stage of disease may be examined in clinical trials in patients with smoldering MM, and other hematological malignancies with precursor conditions.
journal_name
Leukemiajournal_title
Leukemiaauthors
Moschetta M,Mishima Y,Kawano Y,Manier S,Paiva B,Palomera L,Aljawai Y,Calcinotto A,Unitt C,Sahin I,Sacco A,Glavey S,Shi J,Reagan MR,Prosper F,Bellone M,Chesi M,Bergsagel LP,Vacca A,Roccaro AM,Ghobrial IMdoi
10.1038/leu.2016.3subject
Has Abstractpub_date
2016-05-01 00:00:00pages
1103-15issue
5eissn
0887-6924issn
1476-5551pii
leu20163journal_volume
30pub_type
杂志文章相关文献
LEUKEMIA文献大全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::The authors analyzed twelve patients with symptomatic essential throthrombocythemia (E.T.) diagnosed from 1983 to 1991. Haemorrhagic and thrombotic phenomena were the main presenting features. Treatment consisted mostly of alpha-interferon (IFN-alpha 2b) subcutaneously in dosage ranging from 3 to 5 MU/m2 and hydroxyur...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1992-01-01 00:00:00
abstract::ADMIRE was a multicenter, randomized-controlled, open, phase IIB superiority trial in previously untreated chronic lymphocytic leukemia. Conventional front-line therapy in fit patients is fludarabine, cyclophosphamide and rituximab (FCR). Initial evidence from non-randomized phase II trials suggested that the addition...
journal_title:Leukemia
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1038/leu.2017.65
更新日期:2017-10-01 00:00:00
abstract::v-erb-B is the principal transforming gene of avian erythroblastosis virus, a replication defective retrovirus that transforms erythroid and fibroblast cells in vitro and causes erythroleukemia and fibrosarcoma in vivo. We have used a recombinant murine retrovirus, based on the truncated genome of Moloney murine leuke...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1992-01-01 00:00:00
abstract::Positive selection of CD34+ cells has applications in diagnostic pathology, in peripheral blood and bone marrow transplantation, and in studies on the function and regulation of primitive haemopoietic stem cells. Antibody-coated magnetic microspheres (dynabeads) can be used to isolate these cells by positive selection...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1993-06-01 00:00:00
abstract::Chronic graft-versus-host disease (GVHD) remains a serious complication after allogeneic hematopoietic stem cell transplantation (HCT). In 2005 the National Institutes of Health (NIH) established new criteria for chronic GVHD based on retrospective data and expert recommendations. We prospectively evaluated the incide...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2011.257
更新日期:2012-04-01 00:00:00
abstract::Outcomes after unmanipulated haploidentical stem cell transplantation (Haplo) and after unrelated cord blood transplantation (UCBT) are encouraging and have become alternative options to treat patients with high-risk acute leukemia without human leukocyte antigen (HLA) matched donor. We compared outcomes after UCBT an...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2015.98
更新日期:2015-09-01 00:00:00
abstract::The cell line described here was established for a 50-year-old male patient with rapidly progressive non-Hodgkin's lymphoma whose marrow was diffusely infiltrated with large granular lymphocytes (LGL). Immunophenotyping of marrow blasts and peripheral lymphocytes was positive for CD56, CD2 and CD7, and negative for CD...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1994-04-01 00:00:00
abstract::Signal transducer and activator of transcription (Stat)3 is constitutively activated in cutaneous T-cell lymphoma (CTCL), where it protects tumour cells against apoptosis. The constitutive activation of Stat3 leads to a constitutive expression of suppressor of cytokine signalling (SOCS)-3. In healthy cells, SOCS-3 is ...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2403610
更新日期:2005-02-01 00:00:00
abstract::We have previously shown that chronic lymphocytic leukemia (CLL) B cells secrete vascular endothelial growth factor (VEGF) in vitro, have constitutively active VEGF receptors R1 and R2, and respond to exogenous VEGF by specifically upregulating Mcl-1 and XIAP in association with decreased cell death. We found that epi...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2403667
更新日期:2005-04-01 00:00:00
abstract::To evaluate current detection methods for FIP1L1-PDGFRA in hypereosinophilic syndrome (HES), we developed a means to rapidly amplify genomic break points. We screened 202 cases and detected genomic junctions in all samples previously identified as RT-PCR positive (n=43). Genomic fusions were amplified by single step P...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2008.309
更新日期:2009-02-01 00:00:00
abstract::Ninety-five percent of radiation-induced murine myeloid leukemias contain chromosome 2 aberrations. A dominant molecular defect has not yet been identified: both deletions and breakpoint-specific events have been postulated. We have generated a model in which chromosome 2 lesions have been generated in vitro in a clon...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1995-12-01 00:00:00
abstract::Viral infection induces potent cellular immunity and activated intracellular signaling, which may dictate the driver events involved in immune escape and clonal selection of virus-associated cancers, including Epstein-Barr virus (EBV)-positive lymphomas. Here, we thoroughly interrogated PD-L1/PD-L2-involving somatic a...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/s41375-019-0380-5
更新日期:2019-07-01 00:00:00
abstract::Resistance to anthracyclines is related to a poor prognosis in childhood acute lymphoblastic leukemia (ALL). Resistance to this class of drugs may (partly) be reversed by modulating agents, as has been demonstrated in a variety of cell lines. However, it is unknown which modulators may be of clinical benefit in childh...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2401035
更新日期:1998-06-01 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::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::The antimetabolite 6-thioguanine (6-TG) is utilized in the management of acute myelogenous leukemia (AML). Angiogenesis is a possible therapeutic target in hematologic tumors. Thus, we addressed the possibility that 6-TG may also act as an anti-angiogenic molecule. 6-TG inhibited endothelial cell proliferation trigger...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2402646
更新日期:2002-08-01 00:00:00
abstract::In this study, the long-term outcome of 1818 patients treated in five consecutive clinical trials (the cooperative study group for childhood acute lymphoblastic leukaemia (COALL) 82, 85, 89, 92 and 97) from 24 cooperating centres in Germany is reported. The probability of event-free survival (pEFS) improved significan...
journal_title:Leukemia
pub_type: 临床试验,杂志文章
doi:10.1038/leu.2009.249
更新日期:2010-02-01 00:00:00
abstract::Real-time quantitative polymerase chain reaction (PCR) for BCR-ABL mRNA in the peripheral blood (RQ-PCR) provides an accurate and reliable measure of response to therapy in chronic myeloid leukaemia (CML). We wanted to determine in what circumstances additional clinically relevant information was provided by simultane...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2404139
更新日期:2006-04-01 00:00:00
abstract::Resistant AML encompasses two groups of patients: those with refractory leukemia and those whose leukemia has relapsed. Refractory leukemia is disease that does not respond to initial induction chemotherapy with cytarabine and an anthracycline. Patients with refractory leukemia are likely to have disease with adverse ...
journal_title:Leukemia
pub_type: 杂志文章,评审
doi:
更新日期:1998-09-01 00:00:00
abstract::The altered metabolism of cancer cells is a treasure trove to discover new antitumoral strategies. The gene (SLC7A5) encoding system L amino-acid transporter 1 (LAT1) is overexpressed in murine lymphoma cells generated via T-cell deletion of the pten tumor suppressor, and also in human T-cell acute lymphoblastic leuke...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2014.338
更新日期:2015-06-01 00:00:00
abstract::In 2005, the first guidelines were published on the management of patients with multiple myeloma (MM). An expert panel reviewed the currently available literature as the basis for a set of revised and updated consensus guidelines for the diagnosis and management of patients with MM who are not eligible for autologous ...
journal_title:Leukemia
pub_type: 杂志文章,实务指引,评审
doi:10.1038/leu.2009.122
更新日期:2009-10-01 00:00:00
abstract::CD40 is a surface glycoprotein, member of the nerve growth factor receptor family, which is expressed on B cells and plays an important role in their development, growth, and differentiation. Using chromosomal in situ hybridization, we localized the CD40 gene to the long arm of chromosome 20, bands q12-q13.2. This loc...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1994-07-01 00:00:00
abstract::Activation of the MEK/ERK/MAP kinase signaling pathway promotes the proliferation and survival of hematopoietic cells. The kinases MEK-1, MEK-2, ERK-1/MAPK and ERK-2/MAPK are activated by phosphorylation at specific sites, and these events can be monitored using phospho-specific antibodies. In this report we examined ...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2402400
更新日期:2002-04-01 00:00:00
abstract::All-trans retinoic acid has recently been shown to induce differentiation of acute promyelocytic leukemia cells in vitro and in vivo. Clinical trials of patients treated de novo, in first relapse, and with resistant disease have achieved a high rate of complete remission (CR). The overall toxicity is substantially les...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1992-06-01 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::A consecutive population-based series of 372 adult acute myeloid leukemias, successfully cytogenetically investigated at a single center between 1976 and 1993, is reported. All medical records were reviewed in order to ascertain the prognostic impact of karyotype, divided into three groups; favorable (t(8;21), t(15;17...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2401788
更新日期:2000-06-01 00:00:00
abstract::Myeloid neoplasms are characterized by frequent mutations in at least seven components of the spliceosome that have distinct roles in the process of pre-mRNA splicing. Hotspot mutations in SF3B1, SRSF2, U2AF1 and loss of function mutations in ZRSR2 have revealed widely different aberrant splicing signatures with littl...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/s41375-020-1002-y
更新日期:2020-08-04 00:00:00
abstract::Fludarabine phosphate (2-F-ara-AMP) is an adenine nucleoside analogue that shows significant activity against chronic lymphocytic leukemia and indolent lymphoma. We assessed the cytotoxic interaction produced by the combination of the active metabolite of fludarabine phosphate, fludarabine (9-beta-D-arabinofuranosyl-2...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2401684
更新日期:2000-03-01 00:00:00
abstract::Previous studies have revealed a consistent defect in the cycling behavior of primitive neoplastic progenitor cells in patients with Philadelphia chromosome (Ph1)-positive chronic myeloid leukemia (CML). This is manifested both in vivo and in long-term cultures of CML cells as an increased rate of turnover amongst Ph1...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1991-10-01 00:00:00