Variability in responsiveness to lovastatin of the primitive CD34+ AML subfraction compared to normal CD34+ cells.

Abstract:

:In the present study, we questioned whether the cholesterol synthesis inhibitor lovastatin potentiates the cytotoxicity of chemotherapeutic agents in the primitive CD34(+) subpopulation of acute myeloid leukemia (AML) cells. AML mononuclear cells (n = 17) were sorted in CD34(+) and CD34(-) fractions and compared to normal CD34(+/-) cells (n = 7). The percentage of surviving cells upon exposure to lovastatin (25-100 microM) and/or chemotherapeutics (cytarabin or daunorubicin) was determined with a luminescent cell viability assay. The results demonstrate that the primitive CD34(+) subpopulation of normal and AML cells displayed a higher sensitivity to lovastatin than the more mature CD34(-) subpopulation. The combination of lovastatin and chemotherapeutics resulted in a more pronounced inhibitory effect on both subpopulations. In contrast to the homogeneous results in normal CD34(+) cells, a distinct heterogeneity in lovastatin sensitivity was found in AML samples. Therefore, a group of normal (n = 11) and abnormal (n = 6) responders were identified based on a reduced or increased cell survival compared to normal CD34(+) cells. This distinction was not only observed in the CD34(+) AML subfraction but also in CD34(+)CD38(-)AML cells. In the abnormal responder group, 50% of patients presented with unfavorable cytogenetics and significant higher peripheral blast cell counts, which coincided with poor treatment results. In summary, the findings indicate that the primitive subfraction of CD34(+) AML cells is in the majority of cases affected by lovastatin treatment, which is potentiated when combined with chemotherapeutics. Heterogeneity of the response observed in AML patients allowed identification of a subgroup with poor prognosis.

journal_name

Ann Hematol

journal_title

Annals of hematology

authors

de Jonge-Peeters SD,van der Weide K,Kuipers F,Sluiter WJ,de Vries EG,Vellenga E

doi

10.1007/s00277-008-0633-2

subject

Has Abstract

pub_date

2009-06-01 00:00:00

pages

573-80

issue

6

eissn

0939-5555

issn

1432-0584

journal_volume

88

pub_type

杂志文章
  • Notch1 signaling is irresponsible to the anti-leukemic effect of HDACis in B-ALL Nalm-6 cells.

    abstract::B cell acute lymphoblastic leukemia (B-ALL) is an aggressive hematologic malignancy with limited treatment strategies. Histone deacetylases inhibitors (HDACis) are promising novel tools for cancer therapy, whose anti-tumor effects and the underlying mechanisms on B-ALL remain to be elucidated. Recently, Notch1 signali...

    journal_title:Annals of hematology

    pub_type: 杂志文章

    doi:10.1007/s00277-012-1561-8

    authors: Shao N,Ma D,Wang J,Lu T,Guo Y,Ji C

    更新日期:2013-01-01 00:00:00

  • The beta-globin genotype E121Q/W15X (cd121GAA-->CAA/cd15TGG-->TGA) underlines Hb d/beta-(0) thalassaemia marked by domination of haemoglobin D.

    abstract::Among 13,525 haemoglobin analyses performed in our laboratory we detected 21 cases of haemoglobin D (Hb D) disease. Investigation of a family affected with this abnormal haemoglobin revealed two cases of Hb D/beta-(0) thalassaemia for the first time among Saudi Arabs. The two patients were diagnosed as having chronic ...

    journal_title:Annals of hematology

    pub_type: 杂志文章

    doi:10.1007/s002770100376

    authors: Ahmed M,Stuhrmann M,Bashawri L,Kühnau W,El-Harith EH

    更新日期:2001-11-01 00:00:00

  • Headache prevalence following recovery from TTP and aHUS.

    abstract::Thrombotic thrombocytopenia purpura (TTP) and atypical hemolytic uremic syndromes (aHUS) are distinct clinical disorders characterized by hemolytic anemia, thrombocytopenia, microthrombi, and end organ damage. TTP is characterized by a low ADAMTS13 activity level at diagnosis of <10 % ADAMTS13 activity, while aHUS is ...

    journal_title:Annals of hematology

    pub_type: 临床试验,杂志文章

    doi:10.1007/s00277-015-2411-2

    authors: Saultz JN,Wu HM,Cataland S

    更新日期:2015-09-01 00:00:00

  • Stroke prevention in the young child with sickle cell anaemia.

    abstract::Cerebrovascular disease resulting in stroke is a serious and preventable complication of sickle cell anaemia (SCA). Children at high risk of preventable stroke can be identified by transcranial Doppler ultrasound (TCD). Current guidelines in the UK recommend annual TCD screening from 3 years, although studies suggest ...

    journal_title:Annals of hematology

    pub_type: 杂志文章

    doi:10.1007/s00277-009-0757-z

    authors: Roberts L,O'Driscoll S,Dick MC,Height SE,Deane C,Goss DE,Pohl K,Rees DC

    更新日期:2009-10-01 00:00:00

  • Familial hematological malignancies: new IDH2 mutation.

    abstract::Isocitrate dehydrogenase IDH 1 and IDH 2 mutations were reported in several cancer forms, especially in hematological malignancies, but were never been investigated in familial aggregation. The aim of this study is to determine whether germline isocitrate dehydrogenase genes mutations are involved.We targeted IDH1 and...

    journal_title:Annals of hematology

    pub_type: 杂志文章

    doi:10.1007/s00277-016-2813-9

    authors: Hamadou WS,Bourdon V,Létard S,Brenet F,Laarif S,Besbes S,Paci A,David M,Penard-Lacronique V,Youssef YB,Laatiri MA,Eisinger F,Mari V,Gesta P,Dreyfus H,Bonadona V,Dugast C,Zattara H,Faivre L,Noguchi T,Khélif A,Sal

    更新日期:2016-12-01 00:00:00

  • Human peripheral blood mononuclear cells require factor X and platelets for expression of prothrombinase activity in response to bacterial lipopolysaccharide.

    abstract::We investigated whether human peripheral blood mononuclear cells (PBMC) express prothrombinase following stimulation with bacterial lipopolysaccharide (LPS). LPS-stimulated PBMC devoid of contaminating platelets failed to activate prothrombin directly. Addition of platelets did not result in expression of prothrombina...

    journal_title:Annals of hematology

    pub_type: 杂志文章

    doi:10.1007/s002770100288

    authors: Pejler G,Geczy CL

    更新日期:2001-05-01 00:00:00

  • Reduced frequency treatment with bortezomib plus dexamethasone for elderly patients with relapsed and/or refractory multiple myeloma: a phase 2 study of the Japanese Myeloma Study Group (JMSG-0902).

    abstract::Bortezomib is one of the most widely used novel drugs for the treatment of multiple myeloma (MM). However, twice-weekly intravenous administration is associated with innegligible adverse events and treatment discontinuation. We therefore evaluated the long-term efficacy and feasibility of reduced frequency treatment w...

    journal_title:Annals of hematology

    pub_type: 杂志文章,多中心研究

    doi:10.1007/s00277-016-2661-7

    authors: Ozaki S,Hata H,Abe M,Saitoh T,Hanamura I,Yano H,Sunami K,Kosugi H,Sawamura M,Nakazato T,Masunari T,Mori M,Takagi T,Murakami H,Shimizu K

    更新日期:2016-05-01 00:00:00

  • Myelodysplastic patients with raised percentage of hypochromic red cells have evidence of functional iron deficiency.

    abstract::Raised percentage hypochromic red cells (%HRC) were detected at diagnosis in 10 of 34 consecutive patients with low-risk myelodysplastic syndrome (MDS) [refractory anemia (RA) (4/26) and RA with ring sideroblasts (6/8)], all of whom had normal or increased serum ferritin and bone marrow iron stores. Elevated %HRC has ...

    journal_title:Annals of hematology

    pub_type: 杂志文章

    doi:10.1007/s00277-006-0107-3

    authors: Murphy PT,Quinn JP,O'Donghaile D,Swords R,O'Donnell JR

    更新日期:2006-07-01 00:00:00

  • Transdifferentiation of mesenchymal stem cells into cardiomyocytes by direct cell-to-cell contact with neonatal cardiomyocyte but not adult cardiomyocytes.

    abstract::Recent studies have demonstrated that direct cell-to-cell interaction is one of the microenvironment factors for transdifferentiation of adult stem cells into cardiomyocytes. We investigated whether transdifferentiation of mesenchymal stem cells (MSCs) into cardiomyocytes was dependent on developmental stages of cocul...

    journal_title:Annals of hematology

    pub_type: 杂志文章

    doi:10.1007/s00277-005-1068-7

    authors: Yoon J,Shim WJ,Ro YM,Lim DS

    更新日期:2005-10-01 00:00:00

  • Meis1 is critical to the maintenance of human acute myeloid leukemia cells independent of MLL rearrangements.

    abstract::Although the outcome of patients with acute myeloid leukemia (AML) has improved by optimized chemotherapy regimens and bone marrow transplantation, leukemia relapse remains one of the most challenging problems during therapy. Sustained existence of AML blasts is a fundamental determinant for the development of leukemi...

    journal_title:Annals of hematology

    pub_type: 杂志文章

    doi:10.1007/s00277-016-2913-6

    authors: Liu J,Qin YZ,Yang S,Wang Y,Chang YJ,Zhao T,Jiang Q,Huang XJ

    更新日期:2017-04-01 00:00:00

  • Temsirolimus acts as additive with bendamustine in aggressive lymphoma.

    abstract::The mammalian target of rapamycin (mTOR) is a protein kinase involved in the phosphatidylinositol 3-kinase (PI3K)/AKT signalling pathway. It plays a pivotal role in the control of cell proliferation, survival, and angiogenesis with multiple and frequent dysregulations of this pathway in human tumors. Temsirolimus is a...

    journal_title:Annals of hematology

    pub_type: 杂志文章

    doi:10.1007/s00277-015-2570-1

    authors: Zoellner AK,Weiglein T,Hutter G,Zimmermann Y,Cieplik HC,Hess G,Dreyling M

    更新日期:2016-02-01 00:00:00

  • Prevalence of increased osmotic fragility of erythrocytes in German blood donors: screening using a modified glycerol lysis test.

    abstract::We screened for increased osmotic fragility of erythrocytes in 1464 healthy German blood donors. The osmotic fragility was determined by an acidified glycerol lysis test (AGLT) using glycerol-sodium phosphate-buffered NaCl solution. Since the original test described by Zanella et al. [23] showed only low specificity f...

    journal_title:Annals of hematology

    pub_type: 杂志文章

    doi:10.1007/BF01715351

    authors: Eber SW,Pekrun A,Neufeldt A,Schröter W

    更新日期:1992-02-01 00:00:00

  • Blood leukocyte subsets and cytokine profile after autologous peripheral blood stem cell transplantation.

    abstract::High-dose chemotherapy with autologous peripheral blood stem cell transplantation (PBSCT) includes the risk of infectious complications due to neutropenia and therapy-induced immune deviation. In order to understand early immune recovery in this situation, we analyzed the distribution of cell subsets by flow cytometry...

    journal_title:Annals of hematology

    pub_type: 杂志文章

    doi:10.1007/s00277-003-0716-z

    authors: Krause SW,Rothe G,Gnad M,Reichle A,Andreesen R

    更新日期:2003-10-01 00:00:00

  • Features of extramedullary myeloma relapse: high proliferation, minimal marrow involvement, adverse cytogenetics: a retrospective single-center study of 24 cases.

    abstract::Extramedullary (e) relapse in multiple myeloma(MM) has an adverse prognosis, but knowledge concerning biological features and preferred treatment is scarce. We screened the myeloma registry of our institution for eMM relapses and identified 24 cases among 357 patients (pts).Only 8% of eMM relapses occurred after initi...

    journal_title:Annals of hematology

    pub_type: 杂志文章

    doi:10.1007/s00277-012-1414-5

    authors: Rasche L,Bernard C,Topp MS,Kapp M,Duell J,Wesemeier C,Haralambieva E,Maeder U,Einsele H,Knop S

    更新日期:2012-07-01 00:00:00

  • Rapid improvement of disseminated aspergillosis with caspofungin/voriconazole combination in an adult leukemic patient.

    abstract::A 57-year-old man with acute myeloid leukemia (AML) French-American-British (FAB) 4 developed disseminated invasive cerebral and pulmonary aspergillosis during postinduction aplasia. According to international consensus, infection was categorized as probable (two host factors: deep neutropenia for >10 days and refract...

    journal_title:Annals of hematology

    pub_type: 杂志文章

    doi:10.1007/s00277-003-0792-0

    authors: Damaj G,Ivanov V,Le Brigand B,D'incan E,Doglio MF,Bilger K,Faucher C,Vey N,Gastaut JA

    更新日期:2004-06-01 00:00:00

  • Bone marrow findings in blast phase of polycythemia vera.

    abstract::Approximately 10% of patients with polycythemia vera (PV) transform to acute leukemia (blast phase) at 10 years after initial diagnosis of PV. The bone marrow pathologic, cytogenetic, and molecular features of blast phase have not been well characterized. In this study, we reviewed 422 PV patients over a period of 11 ...

    journal_title:Annals of hematology

    pub_type: 杂志文章

    doi:10.1007/s00277-017-3211-7

    authors: Hidalgo López JE,Carballo-Zarate A,Verstovsek S,Wang SA,Hu S,Li S,Xu J,Zuo W,Tang Z,Yin CC,Medeiros LJ,Bueso-Ramos CE,Tang G

    更新日期:2018-03-01 00:00:00

  • Valproic acid: an old drug newly discovered as inhibitor of histone deacetylases.

    abstract::Fusion proteins encoded by several types of chromosomal translocations in promyelocytic leukemia can serve as aberrant transcriptional repressors relying on recruitment of histonedeacetylases (HDACs) into DNA-associated multi-protein complexes. Thus, inappropriate modulation of chromatin structure by HDACs and subsequ...

    journal_title:Annals of hematology

    pub_type: 杂志文章,评审

    doi:10.1007/s00277-004-0850-2

    authors: Göttlicher M

    更新日期:2004-01-01 00:00:00

  • Prevalence and clinical impact of autoimmune diseases and chronic infections in malignant lymphomas at diagnosis.

    abstract::There is increasing evidence for the role of chronic antigenic stimulation (CS) in the development of cancer. Clinical data, however, are rare as is the information on outcome. In this study, the occurrence of chronic infections (CI) and autoimmune diseases (AI) in patients with malignant lymphoma at diagnosis was ass...

    journal_title:Annals of hematology

    pub_type: 杂志文章

    doi:10.1007/s00277-011-1178-3

    authors: Vanura K,Späth F,Gleiss A,Le T,Porpaczy E,Skrabs C,Hauswirth A,Fleiss K,Wessely F,Gaiger A,Müllauer L,Jäger U

    更新日期:2011-08-01 00:00:00

  • Clinical heterogeneity of silent-gene b-thalassemia among Indians.

    abstract::This paper describes six Indian families in which silent-gene beta-thalassemia was encountered by us in the past 2 years. This stresses the importance of globin-chain synthesis in the diagnosis of beta-thalassemia. Of these six cases, five were diagnosed retrospectively when they had a homozygous beta-thalassemia offs...

    journal_title:Annals of hematology

    pub_type: 杂志文章

    doi:10.1007/BF01715386

    authors: Nadkarni A,Pawar A,Mudera VC,Mohanty D,Colah R

    更新日期:1995-01-01 00:00:00

  • Early CMV replication and subsequent chronic GVHD have a significant anti-leukemic effect after allogeneic HSCT in acute myeloid leukemia.

    abstract::Early cytomegalovirus (CMV) replication (eCMV) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been suggested as an independent factor that reduces leukemia relapse risk. We retrospectively analyzed 74 patients with acute myeloid leukemia (AML) who underwent allo-HSCT between August 2006 and S...

    journal_title:Annals of hematology

    pub_type: 杂志文章

    doi:10.1007/s00277-014-2190-1

    authors: Jang JE,Kim SJ,Cheong JW,Hyun SY,Kim YD,Kim YR,Kim JS,Min YH

    更新日期:2015-02-01 00:00:00

  • Absolute monocyte count is a predictor of overall survival and progression-free survival in nodal peripheral T cell lymphoma.

    abstract::Nodal peripheral T cell lymphomas (nPTCL) present aggressive clinical course, and its heterogeneous nature and poor prognosis with current therapeutic strategies make it a target for the development of new prognostic markers. Thus, we investigated tumor-associated macrophages (TAM) according to the number of cells exp...

    journal_title:Annals of hematology

    pub_type: 临床试验,杂志文章

    doi:10.1007/s00277-019-03731-w

    authors: de Pádua Covas Lage LA,Hamasaki DT,Moreira FR,Rocha V,Zerbini MCN,Pereira J

    更新日期:2019-09-01 00:00:00

  • Cationic lipid mediated transfer of c-abl and bcr antisense oligonucleotides to immature normal myeloid cells: uptake, biological effects and modulation of gene expression.

    abstract::Uptake and biochemical and biological effects of antisense oligodeoxynucleotides (ODN) specific for c-abl and bcr genes were studied in normal immature myeloid cells. CD34-positive cells were purified by positive and negative selection and cultured in liquid culture for 7 days. These cells were then incubated with ODN...

    journal_title:Annals of hematology

    pub_type: 杂志文章

    doi:10.1007/BF00641311

    authors: Albrecht T,Schwab R,Peschel C,Engels HJ,Fischer T,Huber C,Aulitzky WE

    更新日期:1996-02-01 00:00:00

  • Immune thrombocytopenia and Fc receptor-mediated phagocyte function.

    abstract::The response to intravenous immunoglobulin treatment (IVIG) is thought, in part, to be due to blockade of Fc receptor for IgG in the mononuclear phagocyte system (MPS). We have studied this by measuring splenic clearance of heat-damaged and IgG antibody-coated red cells in immune thrombocytopenic patients receiving IV...

    journal_title:Annals of hematology

    pub_type: 杂志文章

    doi:10.1007/BF01698483

    authors: Newland AC,Macey MG

    更新日期:1994-08-01 00:00:00

  • Antiapoptotic effect of interleukin-2 (IL-2) in B-CLL cells with low and high affinity IL-2 receptors.

    abstract::Although B chronic lymphocytic leukemia (B-CLL) cells express the alpha chain of the interleukin-2 (IL-2) receptor CD25, little is known about the effect of IL-2 on apoptosis in B-CLL cells. We have shown previously that stimulation of B-CLL cells with a CpG-oligonucleotide induces IL-2 high affinity receptors. In our...

    journal_title:Annals of hematology

    pub_type: 杂志文章

    doi:10.1007/s00277-010-0994-1

    authors: Decker T,Bogner C,Oelsner M,Peschel C,Ringshausen I

    更新日期:2010-11-01 00:00:00

  • Prevalence of chronic idiopathic neutropenia of adults among an apparently healthy population living on the island of Crete.

    abstract::The aim of the present study was to investigate the prevalence of chronic idiopathic neutropenia of adults (CINA) among an apparently healthy population born and living on the island of Crete. The study was carried out with 778 subjects, 392 men aged 16-78 years (median 43 years) and 386 women aged 15-79 years (median...

    journal_title:Annals of hematology

    pub_type: 杂志文章

    doi:10.1007/s002770050518

    authors: Papadaki HA,Xylouri I,Coulocheri S,Kalmanti M,Kafatos A,Eliopoulos GD

    更新日期:1999-07-01 00:00:00

  • Low-density lipoprotein cholesterol suppresses apoptosis in human multiple myeloma cells.

    abstract::Multiple myeloma (MM) is an incurable disease accompanied by low plasma levels of low-density lipoprotein cholesterol (LDL-c). The significance of altered cholesterol metabolism in the pathophysiology of MM remains elusive. Although it has been hypothesized that myeloma cells depend on exogenous cholesterol for its su...

    journal_title:Annals of hematology

    pub_type: 杂志文章

    doi:10.1007/s00277-011-1246-8

    authors: Tirado-Vélez JM,Benítez-Rondán A,Cózar-Castellano I,Medina F,Perdomo G

    更新日期:2012-01-01 00:00:00

  • Intermediate intensity conditioning regimen containing FLAMSA, treosulfan, cyclophosphamide, and ATG for allogeneic stem cell transplantation in elderly patients with relapsed or high-risk acute myeloid leukemia.

    abstract::Lower dosage of total body irradiation (TBI) and chemotherapy in reduced-intensity conditioning (RIC) regimens prior to allogeneic stem cell transplantation have reduced the toxicity of the conditioning and non-relapse mortality. The FLAMSA-RIC protocol for high-risk patients with acute myeloid leukemia (AML) and myel...

    journal_title:Annals of hematology

    pub_type: 杂志文章

    doi:10.1007/s00277-011-1253-9

    authors: Chemnitz JM,von Lilienfeld-Toal M,Holtick U,Theurich S,Shimabukuro-Vornhagen A,Krause A,Brossart P,Hallek M,Scheid C

    更新日期:2012-01-01 00:00:00

  • Mechanism of thrombocytopenia in COVID-19 patients.

    abstract::Since December 2019, a novel coronavirus has spread throughout China and across the world, causing a continuous increase in confirmed cases within a short period of time. Some studies reported cases of thrombocytopenia, but hardly any studies mentioned how the virus causes thrombocytopenia. We propose several mechanis...

    journal_title:Annals of hematology

    pub_type: 杂志文章,评审

    doi:10.1007/s00277-020-04019-0

    authors: Xu P,Zhou Q,Xu J

    更新日期:2020-06-01 00:00:00

  • Hydroxyurea in thalassemia intermedia--a promising therapy.

    abstract::Pharmacological agents such as hydroxyurea (HU) have been known to cause induction of fetal hemoglobin and possibly may alleviate the symptoms in thalassemia intermedia patients. Thirty-seven patients with beta-thalassemia intermedia were enrolled to assess response to HU therapy. Major response was defined as transfu...

    journal_title:Annals of hematology

    pub_type: 临床试验,杂志文章

    doi:10.1007/s00277-005-1026-4

    authors: Dixit A,Chatterjee TC,Mishra P,Choudhry DR,Mahapatra M,Tyagi S,Kabra M,Saxena R,Choudhry VP

    更新日期:2005-07-01 00:00:00

  • Immunomagnetic enrichment of CD138 positive cells from weakly infiltrated myeloma patients samples enables the determination of the tumor clone specific IgH rearrangement.

    abstract::In multiple myeloma, the polymerase chain reaction (PCR) of the Ig heavy chain with allele-specific oligonucleotide (ASO) primers is a common and well-described method of identifying the tumor clone in peripheral blood (PB), bone marrow (BM) or leukapheresis products (LA). A factor which is crucial to the detection of...

    journal_title:Annals of hematology

    pub_type: 杂志文章

    doi:10.1007/s002770000245

    authors: Draube A,Pfister R,Vockerodt M,Schuster S,Kube D,Diehl V,Tesch H

    更新日期:2001-02-01 00:00:00