Abstract:
:Neomorphic mutations in isocitrate dehydrogenase 1 (IDH1) are frequently found in several human cancer types including acute myeloid leukemia (AML) and lead to the production of high levels of the oncometabolite (R)-2-hydroxyglutarate (R-2HG). Here we report the characterization of BAY1436032, a novel pan-mutant IDH1 inhibitor, both in vitro and in vivo. BAY1436032 specifically inhibits R-2HG production and colony growth, and induces myeloid differentiation of AML cells carrying IDH1R132H, IDH1R132C, IDH1R132G, IDH1R132L and IDH1R132S mutations. In addition, the compound impacts on DNA methylation and attenuates histone hypermethylation. Oral administration of BAY1436032 led to leukemic blast clearance, myeloid differentiation, depletion of leukemic stem cells and prolonged survival in two independent patient-derived xenograft IDH1 mutant AML mouse models. Together, BAY1436032 is highly effective against all major types of IDH1 mutant AML.
journal_name
Leukemiajournal_title
Leukemiaauthors
Chaturvedi A,Herbst L,Pusch S,Klett L,Goparaju R,Stichel D,Kaulfuss S,Panknin O,Zimmermann K,Toschi L,Neuhaus R,Haegebarth A,Rehwinkel H,Hess-Stumpp H,Bauser M,Bochtler T,Struys EA,Sharma A,Bakkali A,Geffers R,Aradoi
10.1038/leu.2017.46subject
Has Abstractpub_date
2017-10-01 00:00:00pages
2020-2028issue
10eissn
0887-6924issn
1476-5551pii
leu201746journal_volume
31pub_type
杂志文章相关文献
LEUKEMIA文献大全abstract::The pleiotropic cytokines, interleukin (IL)-1 alpha, type I interferons and IL-6 also act on cells involved in antibody production. Somehow the immunologic tolerance to these cytokines is often spontaneously broken--even in healthy individuals. Thus, relatively high concentrations of high affinity IgG antibodies again...
journal_title:Leukemia
pub_type: 杂志文章,评审
doi:
更新日期:1995-07-01 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
abstract::We have established an erythropoietin-dependent human leukemia cell line, AS-E2, from a patient with acute myeloid leukemia. These cells have many characteristics of late erythroid progenitor cells, they are positive for CD36, Glycophorin A, and CD71 but negative for CD41, and positive for benzidine and PAS staining. ...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2400838
更新日期:1997-11-01 00:00:00
abstract::The flow cytometric detection of minimal residual disease (MRD) in precursor-B-acute lymphoblastic leukemias (precursor-B-ALL) mainly relies on the identification of minor leukemic cell populations that can be discriminated from their normal counterparts on the basis of phenotypic aberrancies observed at diagnosis. Th...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2402150
更新日期:2001-08-01 00:00:00
abstract::The presence of CD19 in myelomatous plasma cells (MM-PCs) correlates with adverse prognosis in multiple myeloma (MM). Although CD19 expression is upregulated by CD81, this marker has been poorly investigated and its prognostic value in MM remains unknown. We have analyzed CD81 expression by multiparameter flow cytomet...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2012.42
更新日期:2012-08-01 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 lens epithelium-derived growth factor (LEDGF/p75) tethers the mixed-lineage leukemia (MLL1) protein complex to chromatin. Likewise, LEDGF/p75 tethers the HIV-1 pre-integration complex to chromatin. We previously demonstrated that expression of the C-terminal fragment fused to enhanced green fluorescent protein (eG...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2013.10
更新日期:2013-06-01 00:00:00
abstract::Fourteen patients with abnormalities of chromosome 16q, 13 with acute myelogenous leukaemia (AML), and one with refractory anaemia with excess of blasts (RAEB), are described. Seven patients had inv(16)(p13q22), two had del(16)(q22), and five had other abnormalities of 16q. Six of the seven patients with inv(16) had A...
journal_title:Leukemia
pub_type: 杂志文章,评审
doi:
更新日期:1992-12-01 00:00:00
abstract::Retroviral gene transfer into hematopoietic cells has many experimental as well as clinical applications. Although transduction efficiency of retroviral vectors is higher than with conventional methods, selection of successfully transduced cells may become mandatory for efficient in vivo transfer. We have been evaluat...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1995-10-01 00:00:00
abstract::A higher frequency of acute promyelocytic leukemia (APL) has been noted in countries of Southern Europe and among 'Latino' patients of the United States with acute myeloid leukemia (AML). In order to discover whether there is any genetic predisposition to the disease, we analyzed microsatellites flanking PML and RARal...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2402525
更新日期:2002-07-01 00:00:00
abstract::A case of an infant male with Down's syndrome, pancytopenia, and a relative lymphocytosis is presented. A bone marrow aspirate and crushed marrow biopsy were evaluated by microscopy and flow cytometry. A population of immature lymphoid cells positive for CD10 (CALLA) and CD19 (Leu 12) was initially interpreted as sugg...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1993-11-01 00:00:00
abstract::Hematopoietic stem cell transplantation is becoming an increasingly important approach to treatment of different malignant and non-malignant disorders. There is thus growing demand for diagnostic assays permitting the surveillance of donor/recipient chimerism posttransplant. Current techniques are heterogeneous, rende...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2012.66
更新日期:2012-08-01 00:00:00
abstract::Polymerase chain reaction (PCR) techniques utilizing clonospecific T cell receptor (TCR) gamma or delta junctional regions constitute broadly applicable strategies to study the clinical relevance of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL) patients. For the majority of cases current PCR pro...
journal_title:Leukemia
pub_type: 临床试验,杂志文章
doi:
更新日期:1995-02-01 00:00:00
abstract::Hemizygous deletions are common molecular abnormalities in cancer. In some cases, these deletions highlight chromosomal loci containing tumor suppressor genes that undergo homozygous inactivation. In other cases, hemizygous deletions cause disease by allelic insufficiency for one or more genes. As the intact allele ha...
journal_title:Leukemia
pub_type: 杂志文章,评审
doi:10.1038/leu.2009.53
更新日期:2009-07-01 00:00:00
abstract::Self-renewal, as defined by the capacity to yield new colonies following replating, is an important function of leukemic progenitors (L-CFU) to originate self-maintaining clones. In this work, we studied the effect of hyperthermia (41-44 degrees C) on the growth of human L-CFU derived primary colonies and of secondary...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1991-04-01 00:00:00
abstract::This phase 1 dose-escalation study evaluated pomalidomide, bortezomib (subcutaneous (SC) or intravenous (IV)) and low-dose dexamethasone (LoDEX) in lenalidomide-refractory and proteasome inhibitor-exposed relapsed or relapsed and refractory multiple myeloma (RRMM). In 21-day cycles, patients received pomalidomide (1-4...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2017.173
更新日期:2017-12-01 00:00:00
abstract::We studied the organization, diversification and clinical significance of the immunoglobulin light chain (IgL) variable region genes expressed in 17 kappa-chain and 16 lambda-chain producing multiple myeloma (MM) samples. The V genes from 31 MM samples had over 84.9% homology to the known germline Vkappa/lambda genes,...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2400972
更新日期:1998-04-01 00:00:00
abstract::The LH2 gene encodes a putative transcription factor containing two N-terminal LIM and one C-terminal HOX domains. The LH2 locus was mapped to 9q33-34.1, centromeric to the ABL gene. In a recent report, it was suggested that high levels of LH2 expression are consistently observed in chronic myeloid leukemia (CML) pati...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1996-07-01 00:00:00
abstract::We have shown a new phenomenon demonstrating that BALB/c female mice mated to C57BL/6 males during a year (7-10 pregnancies) develop AIDS-like disease or acute leukemia after an additional immunization with fixed ConA activated paternal (C57BL/6) lymphocytes. The AIDS-like disease is sexually and vertically transmissi...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1997-04-01 00:00:00
abstract::Donor leukocyte infusions (DLI) have turned out to be an efficient way to re-establish complete remission (CR) in chronic myeloid leukemia (CML) patients relapsing after allogeneic bone marrow transplantation (BMT). In these patients, absence of PCR bcr-abl fusion transcripts confirmed the potency of donor leukocytes ...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2401144
更新日期:1998-11-01 00:00:00
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::Myeloproliferative neoplasm (MPN)-associated myelofibrosis is a MPN characterized by bone marrow fibrosis, cytopenias, splenomegaly and constitutional symptoms. Pomalidomide, an immune-modifying drug, is reported to improve anaemia and thrombocytopenia in some patients with MPN-associated myelofibrosis. We designed a ...
journal_title:Leukemia
pub_type: 杂志文章,多中心研究
doi:10.1038/leu.2016.299
更新日期:2017-04-01 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
abstract::The aim was to determine the efficacy and safety of decitabine in the settings of relapse post-allogeneic progenitor cell transplantation or as part of the conditioning regimen. Three patients (two AML, one ALL) received single agent decitabine 1000 mg/m2 total dose) for treatment of relapse post-transplant (group 1)....
journal_title:Leukemia
pub_type: 临床试验,杂志文章
doi:
更新日期:1997-03-01 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::Most modern treatment protocols for acute lymphoblastic leukaemia (ALL) include the analysis of minimal residual disease (MRD). To ensure comparable MRD results between different MRD-polymerase chain reaction (PCR) laboratories, standardization and quality control are essential. The European Study Group on MRD detecti...
journal_title:Leukemia
pub_type: 杂志文章,多中心研究
doi:10.1038/sj.leu.2404586
更新日期:2007-04-01 00:00:00
abstract::We investigated the hypothesis that gemtuzumab ozogamicin (GO), an anti-CD33 immunotoxin would improve the efficacy of fludarabine/melphalan as a preparative regimen for allogeneic hematopoietic stem cell transplantation (HSCT) in a phase I/II trial. Toxicity was defined as grades III-IV organ damage, engraftment fail...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2405014
更新日期:2008-02-01 00:00:00
abstract::We previously reported the benefit of lomustine addition to conventional chemotherapy in older acute myeloid leukemias with nonadverse chromosomal aberrations in the LAM-SA 2007 randomized clinical trial (NCT00590837). A molecular analysis of 52 genes performed in 330 patients included in this trial, 163 patients bein...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/s41375-020-01031-1
更新日期:2020-09-18 00:00:00
abstract::Disturbances in the regulation of the balance between the fibrinolytic and procoagulant properties of leukemic cells may contribute to the coagulopathy of acute leukemia. The coagulant response to a number of stimuli is regulated by the expression of tissue factor, but the role of the plasminogen activator inhibitors,...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1993-06-01 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