Abstract：
:Identification of agents that target human leukemia stem cells is an important consideration for the development of new therapies. The present study demonstrates that rocaglamide and silvestrol, closely related natural products from the flavagline class of compounds, are able to preferentially kill functionally defined leukemia stem cells, while sparing normal stem and progenitor cells. In addition to efficacy as single agents, flavaglines sensitize leukemia cells to several anticancer compounds, including front-line chemotherapeutic drugs used to treat leukemia patients. Mechanistic studies indicate that flavaglines strongly inhibit protein synthesis, leading to the reduction of short-lived antiapoptotic proteins. Notably though, treatment with flavaglines, alone or in combination with other drugs, yields a much stronger cytotoxic activity toward leukemia cells than the translational inhibitor temsirolimus. These results indicate that the underlying cell death mechanism of flavaglines is more complex than simply inhibiting general protein translation. Global gene expression profiling and cell biological assays identified Myc inhibition and the disruption of mitochondrial integrity to be features of flavaglines, which we propose contribute to their efficacy in targeting leukemia cells. Taken together, these findings indicate that rocaglamide and silvestrol are distinct from clinically available translational inhibitors and represent promising candidates for the treatment of leukemia.
journal_name
Leukemiajournal_title
Leukemiaauthors
Callahan KP,Minhajuddin M,Corbett C,Lagadinou ED,Rossi RM,Grose V,Balys MM,Pan L,Jacob S,Frontier A,Grever MR,Lucas DM,Kinghorn AD,Liesveld JL,Becker MW,Jordan CTdoi
10.1038/leu.2014.93subject
Has Abstractpub_date
2014-10-01 00:00:00pages
1960-8issue
10eissn
0887-6924issn
1476-5551pii
leu201493journal_volume
28pub_type
杂志文章相关文献
LEUKEMIA文献大全abstract：:Acute myeloid leukemia (AML) with 11q23/MLL rearrangement (MLL-r AML) is allocated to the intermediate- or high-risk cytogenetic prognostic category depending on the MLL fusion partner. A more favorable outcome has been reported in patients receiving an allogeneic hematopoietic stem-cell transplantation (alloHSCT), bu...
journal_title：Leukemia
pub_type： 杂志文章,多中心研究
doi：10.1038/leu.2015.143
更新日期：2015-12-01 00:00:00
abstract：:Both conventional chimerism analysis (CCA) and lineage-specific chimerism analysis (LCA) have potential pitfalls as diagnostic means for the detection of minimal residual disease after allogeneic hematopoietic cell transplantation (aHCT). Therefore, the present study examines the results of both methods in order to de...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/sj.leu.2403719
更新日期：2005-05-01 00:00:00
abstract：:The t(9;22)(q34;q11), generating the Philadelphia chromosome (Ph), is found in more than 90% of patients with chronic myeloid leukemia (CML) and in 15-30% of adults with acute lymphoblastic leukemia (ALL). Different groups have recently described the presence of large genomic deletions adjacent to the translocation br...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/sj.leu.2402829
更新日期：2003-03-01 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：:It has been proposed that adoptive immunotherapy, for the treatment of relapsed AML, with cytotoxic T lymphocytes which show a relative specificity for the leukemic cells may have the advantage of maximizing the beneficial anti-leukemic effect whilst minimizing the probability of graft-versus-host disease. In this stu...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/sj.leu.2402013
更新日期：2001-02-01 00:00:00
abstract：:CD44 variant isoforms (CD44v) have been shown to be important factors in adverse prognosis in hematological malignancies. To investigate whether CD44 expression is associated with malignant transformation in multiple myeloma, RNA and protein expression of CD44 standard (CD44s) and CD44v4, v6, v9, v10 containing isofor...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/sj.leu.2401179
更新日期：1998-11-01 00:00:00
abstract：:Following the publication of this article, the authors noted that Patrick M. Vanderboom was inadvertently omitted from the author list. The correct author list is as follows: Sanjay Kumar, David Murray, Surendra Dasari, Paolo Milani, David Barnidge, Benjamin Madden, Patrick M. Vanderboom, Taxiarchis Kourelis, Bonnie A...
journal_title：Leukemia
pub_type： 已发布勘误
doi：10.1038/s41375-019-0405-0
更新日期：2019-04-01 00:00:00
abstract：:The main reason for the unfavorable clinical outcome of BCR-ABL1-positive acute lymphoblastic leukemia (ALL) is genetic instability. However, how normal B-cell precursors acquire the genetic changes that lead to transformation has not yet been completely defined. We investigated the expression of the activation-induce...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/leu.2009.197
更新日期：2010-01-01 00:00:00
abstract：:The translocation t(11;20)(p15;q11) was found as the sole acquired clonal chromosome abnormality in two patients with acute myeloid leukemia. The bone marrow morphology in both cases corresponded to the M2 subtype of the French-American-British (FAB) classification. None of the patients achieved complete remission, an...
journal_title：Leukemia
pub_type： 杂志文章
doi：
更新日期：1988-07-01 00:00:00
abstract：:The Bcr/Abl tyrosine kinase that is expressed from the Philadelphia chromosome protects leukemia cells from apoptosis caused by removal of growth factors or by cytotoxic agents and ionizing irradiation. This resistance to apoptosis is associated with a Bcr/Abl-mediated G2/M delay. Therefore, inhibiting Bcr/Abl signali...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/sj.leu.2401536
更新日期：1999-10-01 00:00:00
abstract：:Basic fibroblast growth factor (bFGF or FGF-2) is an angiogenic and pleiotropic factor involved in the proliferation and differentiation of numerous cell types. It is expressed mostly in tissues of mesoderm and neuroectoderm origin, and plays an important role in the mesoderm induction, together with transforming grow...
journal_title：Leukemia
pub_type： 杂志文章,评审
doi：
更新日期：1995-06-01 00:00:00
abstract：:To address the prognostic value of minimal residual disease (MRD) before unrelated cord blood transplantation (UCBT) in children with acute lymphoblastic leukemia (ALL), we analyzed 170 ALL children transplanted in complete remission (CR) after myeloablative conditioning regimen. In all, 72 (43%) were in first CR (CR1...
journal_title：Leukemia
pub_type： 杂志文章,多中心研究
doi：10.1038/leu.2012.123
更新日期：2012-12-01 00:00:00
abstract：:Little is known about the incidence of and risk factor for late effects of infant leukemia. We evaluated 19 children with acute lymphoblastic leukemia and 15 with acute myeloid leukemia who were diagnosed at age 12 months or younger and have survived for more than 5 years after the diagnosis (median length of follow-u...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/sj.leu.2401818
更新日期：2000-07-01 00:00:00
abstract：:Bryostatin 1 is a macrocyclic lactone activator of protein kinase C which has displayed promising antileukemic potential in pre-clinical studies. We have assessed the effect of bryostatin 1 on the in vitro clonogenic response of leukemic myeloblasts obtained from 12 patients with acute non-lymphocytic leukemia to reco...
journal_title：Leukemia
pub_type： 杂志文章
doi：
更新日期：1991-05-01 00:00:00
abstract：:Modern treatment strategies, consisting of intensive chemotherapy and cranial irradiation, have remarkably improved the prognosis for children with acute lymphoblastic leukemia. However, patients with a potential for cure are at risk of severe acute and late adverse effects of treatment. Furthermore, in 25-30% of pati...
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：10.1038/sj.leu.2402489
更新日期：2002-06-01 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：:Patients with chronic lymphocytic leukemia (CLL) have defects in both cellular and humoral immunity. Since CD152 (CTLA-4) plays a critical role in downregulating T-cell responses, we studied the expression of surface and cytoplasmic CD152 (sCD152 and cCD152, respectively) in freshly isolated T cells from treatment-naï...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/sj.leu.2403907
更新日期：2005-10-01 00:00:00
abstract：:Cladribine has been reported to have little activity in fludarabine- refractory chronic lymphocytic leukemia (CLL). We sought to determine whether resistance to therapy with cladribine in fludarabine-refractory CLL patients represented primary drug resistance or the inability to tolerate the myelosuppression associate...
journal_title：Leukemia
pub_type： 临床试验,杂志文章,多中心研究
doi：10.1038/sj.leu.2402752
更新日期：2003-02-01 00:00:00
abstract：:Monoclonal antibody QBEND10 is reactive with the CD34 antigen in aldehyde-fixed, decalcified, paraffin-embedded bone marrow biopsies. In normal bone marrow it stained endothelial cells lining arterioles and capillaries, sinusoidal (littoral) cells and 0.89% of all haemopoietic cells. QBEND10+ mononuclear cells were se...
journal_title：Leukemia
pub_type： 杂志文章
doi：
更新日期：1991-12-01 00:00:00
abstract：:Philadelphia (Ph) chromosome or the bcr/abl fusion gene is the hallmark of chronic myeloid leukemia (CML) and serves as a prognostic marker during its treatment. Its detection has been primarily done by karyotype analysis of bone marrow cells. The major limitation of the karyotypic technique is an absolute need for me...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/sj.leu.2401383
更新日期：1999-04-01 00:00:00
abstract：:Imatinib is highly effective in newly diagnosed, but not in relapsed, Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL). BCR-ABL tyrosine kinase domain (TKD) mutations are associated with acquired imatinib resistance, but their role in primary resistance is uncertain. Using highly sensitive ligat...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/leu.2012.5
更新日期：2012-07-01 00:00:00
abstract：:In spite of distinct clinical importance, the molecular mechanisms how Additional sex combs-like 1 (ASXL1) mutation contributes to the pathogenesis of premalignant conditions are largely unknown. Here, with newly generated knock-in mice, we investigated the biological effects of the mutant. Asxl1G643fs heterozygous (A...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/s41375-018-0198-6
更新日期：2019-01-01 00:00:00
abstract：:Over a period of six months, we have followed a total of six different EBV-transformed B cell lines, each of which has been infected by the human immunodeficiency virus (HIV-1). The results indicate that all of these lines were initially able to produce progeny HIV-1, but that over time three of them ceased to produce...
journal_title：Leukemia
pub_type： 杂志文章
doi：
更新日期：1988-12-01 00:00:00
abstract：:The CD30+ anaplastic large cell lymphoma (ALCL) represents a new lymphoma entity thought to be related to Hodgkin'S disease (HD), but displaying also its own unique features. Cytogenetic studies of ALCL have demonstrated the presence of a (2;5)(p23;q35) translocation in a substantial number of these cases. Recently, t...
journal_title：Leukemia
pub_type： 杂志文章
doi：
更新日期：1996-01-01 00:00:00
abstract：:Membrane-derived vesicles (MV) are released from the surface of activated eucaryotic cells and exert pleiotropic effects on surrounding cells. Since the maintenance of pluripotency and undifferentiated propagation of embryonic stem (ES) cells in vitro requires tight cell to cell contacts and effective intercellular si...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/sj.leu.2404132
更新日期：2006-05-01 00:00:00
abstract：:Novel approaches have been designed to treat leukemia based on our understanding of the genetic and biochemical lesions present in different malignancies. This meeting report summarizes some of the recent advances in leukemia treatment. Based on the discoveries of cellular oncogenes, chromosomal translocations, monocl...
journal_title：Leukemia
pub_type：
doi：10.1038/sj.leu.2403156
更新日期：2003-12-01 00:00:00
abstract：:Dysplastic hematopoiesis is the morphological hallmark of myelodysplastic syndromes. Dysplastic features in one or more lineages are also found frequently in bone marrow aspirates from patients with de novo AML and have been associated with an unfavorable prognosis. We asked whether dyshematopoiesis is an independent ...
journal_title：Leukemia
pub_type： 杂志文章
doi：
更新日期：1996-06-01 00:00:00
abstract：:Jumping translocations (JT) are characterized by the relocalization of the same part of a donor to several recipient chromosomes. Although JT occasionally are constitutional, most are associated with hematologic malignancies. In such cases, JT usually arise during disease progression and are associated with poor progn...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/sj.leu.2401108
更新日期：1998-09-01 00:00:00
abstract：:Acute myeloid leukemia (AML) with minimal differentiation was usually referred to as acute undifferentiated leukemia in the past. With the help of immunophenotyping, this subtype of leukemia was shown to express myeloid antigens on the blasts and was designated AML-M0 by FAB Cooperative Study Group in 1991. Among the ...
journal_title：Leukemia
pub_type： 临床试验,杂志文章
doi：10.1038/sj.leu.2401521
更新日期：1999-10-01 00:00:00
abstract：:The clinical and cell growth characteristics of 11 children with monosomy 7 presenting as preleukemia (eight cases) or acute nonlymphoblastic leukemia (three cases) were studied. Anemia was common to all patients, with nine showing leukocytosis, seven thrombocytopenia, and one thrombocytosis. There was a striking pred...
journal_title：Leukemia
pub_type： 杂志文章
doi：
更新日期：1987-02-01 00:00:00
