Enhanced topoisomerase II-induced DNA breaks and free radical production by a new anthracycline with potent antileukemic activity.


:In a previous study we reported that a new anthracycline derivative (moflomycin) exhibited a higher antileukemic activity compared to other anthracyclines, such as daunorubicin and doxorubicin. To explain the superior antileukemic effect of moflomycin and to disclose a possible structure-activity relationship, we investigated the three main mechanisms by which anthracyclines are though to exert their antitumor effect: DNA binding, free radical production and topoisomerase II inhibition. The DNA interaction was assessed both by DNA binding and DNA unwinding assays, free radical generation was studied by electron spin resonance, and topoisomerase II interaction by analysis of the stimulation of enzyme-induced DNA breaks. The results showed a higher free radical production and a greater stimulation of topoisomerase II-mediated DNA cleavage by moflomycin than doxorubicin, associated with a lower DNA affinity. The different biochemical characteristics of moflomycin, particularly its interaction with topoisomerase II, are related to the structural modifications performed on the chromophore. These properties, associated with a higher stability of the molecule induced by the presence of an iodine atom on the sugar moiety, are probably responsible for the higher antileukemic activity of this compound.


Leuk Res


Leukemia research


Andrivon W,Saucier JM,Auclair C,Monneret C,Florent JC,Guillosson JJ,Nafziger J




Has Abstract


1996-02-01 00:00:00














  • Involvement of NF-kappaB and glutathione in cytotoxic effects of nitric oxide and taxol on human leukemia cells.

    abstract::Nitric oxide (NO) has been shown to be cytotoxic for normal and transformed cell lines. One of the intracellular targets for NO action is glutathione (GSH). GSH determinates cellular redox potential and modulates several biological events. During oxidative and nitrosative stress, glutathione system imbalance is associ...

    journal_title:Leukemia research

    pub_type: 杂志文章


    authors: Santos-Silva MC,Freitas MS,Assreuy J

    更新日期:2006-02-01 00:00:00

  • The Dana Farber consortium protocol (DFCP) vs. classic Hyper-CVAD for treatment of acute lymphoblastic leukemia in patients

    abstract:BACKGROUND:The use of intensive pediatric protocols for the treatment of ALL is being extended to older adults. AIM OF THE STUDY:Analysis of the efficacy and toxicity results of pediatric DFCP vs. classic Hyper-CVAD protocol for the treatment of patients with ALL < 50 Y. PATIENTS AND METHODS:A retrospective single ce...

    journal_title:Leukemia research

    pub_type: 杂志文章


    authors: Alabdulwahab AS,Elsayed HG,Sherisher MA,Zeeneldin A,Alghamdi K,Elbjeirami WM

    更新日期:2017-09-01 00:00:00

  • KN-62 analogues as potent differentiating agents of HL-60 cells.

    abstract::KN-62, an inhibitor of the calmodulin-dependent protein kinases (CaMKs), enhances the terminal differentiation of retinoic acid sensitive human myeloid leukemia cell lines. In an effort to identify additional CaMK inhibitors that exhibit more potent activity in triggering leukemia cell differentiation, we synthesized ...

    journal_title:Leukemia research

    pub_type: 杂志文章


    authors: Schuler AD,Si J,Mueller L,Simon JA,Collins SJ

    更新日期:2007-05-01 00:00:00

  • Considerations and challenges for patients with refractory and relapsed acute myeloid leukaemia.

    abstract::Despite advances in understanding the complexities of acute myeloid leukaemia (AML), the treatment of refractory or relapsed AML (rrAML) remains a daunting clinical challenge. Numerous clinical trials have failed to identify new treatments or combinations of existing therapies that substantially improve outcomes and s...

    journal_title:Leukemia research

    pub_type: 杂志文章,评审


    authors: Kell J

    更新日期:2016-08-01 00:00:00

  • Anthracycline-induced erythroid differentiation of K562 cells is inhibited by p28, a novel mammalian glutathione-binding stress protein.

    abstract::When exposed to the anthracycline doxorubicin, K562 cells undergo differentiation which is characterized by arrested cell division, an increased mean cell diameter, and the production of hemoglobin. The influence of expression of p28, a low-molecular weight stress protein, on the differentiation of K562 cells was exam...

    journal_title:Leukemia research

    pub_type: 杂志文章


    authors: Kodym R,Calkins PR,Story MD

    更新日期:2001-02-01 00:00:00

  • RAF-1/MEK/ERK pathway regulates ATRA-induced differentiation in acute promyelocytic leukemia cells through C/EBPβ, C/EBPε and PU.1.

    abstract::MEK/ERK signal pathway was required for the differentiation of granulocytes, megakaryocytes and erythrocytes. Recently, MEK/ERK cascade was reported to be involved in all-trans retinoic acid (ATRA) induced differentiation in acute promyelocytic leukemia (APL) cells. However, the upstream and downstream molecules of ME...

    journal_title:Leukemia research

    pub_type: 杂志文章


    authors: Weng XQ,Sheng Y,Ge DZ,Wu J,Shi L,Cai X

    更新日期:2016-06-01 00:00:00

  • Characterization of a 4 lncRNAs-based prognostic risk scoring system in adults with acute myeloid leukemia.

    abstract:PURPOSE:The study aims to develop a prognostic scoring system based on prognostic lncRNAs for acute myeloid leukemia (AML). METHODS:Based on lncRNA expression profiles downloaded from The Cancer Genome Atlas (TCGA), differentially expressed long noncoding RNAs (DELs) between good prognosis and bad prognosis samples we...

    journal_title:Leukemia research

    pub_type: 杂志文章


    authors: Zeng H,Wu H,Yan M,Tang L,Guo X,Zhao X

    更新日期:2020-01-01 00:00:00

  • Beta-2 microglobulin is a strong prognostic factor in patients with DLBCL receiving R-CHOP therapy.

    abstract::Useful prognostic markers for patients with diffuse large B cell lymphoma (DLBCL) have been reported. To identify which biomarker best predicts the prognosis of patients with DLBCL, we performed a retrospective study that included 319 DLBCL patients who had received rituximab, cyclophosphamide, doxorubicin, vincristin...

    journal_title:Leukemia research

    pub_type: 杂志文章


    authors: Miyashita K,Tomita N,Taguri M,Suzuki T,Ishiyama Y,Ishii Y,Nakajima Y,Numata A,Hattori Y,Yamamoto W,Miyazaki T,Tachibana T,Takasaki H,Matsumoto K,Hashimoto C,Takemura S,Yamazaki E,Fujimaki K,Sakai R,Motomura S,Ishi

    更新日期:2015-08-29 00:00:00

  • Reversine triggers mitotic catastrophe and apoptosis in K562 cells.

    abstract::Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasm of the hematopoietic stem cell characterized by presence of the oncoprotein BCR-ABL1, which have constitutive tyrosine kinase activity. BCR-ABL1 activation induces aurora kinase A (AURKA) and aurora kinase B (AURKB) expression, which are serine-thr...

    journal_title:Leukemia research

    pub_type: 杂志文章


    authors: Rodrigues Alves AP,Machado-Neto JA,Scheucher PS,Paiva HH,Simões BP,Rego EM,Traina F

    更新日期:2016-09-01 00:00:00

  • Reduced-intensity conditioning therapy with fludarabine, idarubicin, busulfan and cytarabine for allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia and myelodysplastic syndrome.

    abstract::We retrospectively analyzed allogenic stem cell transplantation (allo-SCT) outcomes in 82 patients with AML or MDS were conditioned with fludarabine, idarubicin, intravenous-busulfan and cytarabine (FIBA) or busulfan and cyclophosphamide (BuCy). Compared to BuCy regimen, reduced intensity conditioning (RIC) with FIBA ...

    journal_title:Leukemia research

    pub_type: 杂志文章


    authors: Gao L,Gao L,Gong Y,Zhang C,Chen XH,Zhang X

    更新日期:2013-11-01 00:00:00

  • Hemopoietic features of splenectomized mice bearing IL-3 producing T cell leukemia.

    abstract::Hemopoietic responses were studied in splenectomized mice after transplantation of the hemopoietic colony stimulating activity producing leukemia, L8313. In non-splenectomized mice, the number of peripheral leukocytes was elevated to 4 x 10(5)/mm3 after transplantation. In contrast, it was below 1.7 x 10(4)/mm3 in spl...

    journal_title:Leukemia research

    pub_type: 杂志文章


    authors: Sawada H,Sugimoto K,Aramaki K,Mori KJ

    更新日期:1989-01-01 00:00:00

  • Unraveling the mechanisms behind iron overload and ineffective hematopoiesis in myelodysplastic syndromes.

    abstract::Myelodysplastic syndromes (MDS) are a group of clonally-acquired blood disorders characterized by ineffective hematopoiesis leading to cytopenias. Red blood cell transfusions are an important component of supportive care in patients with MDS. Prolonged exposure to transfusions can lead to iron overload, which results ...

    journal_title:Leukemia research

    pub_type: 杂志文章,评审


    authors: Angelucci E,Cianciulli P,Finelli C,Mecucci C,Voso MT,Tura S

    更新日期:2017-11-01 00:00:00

  • Karyotype at diagnosis, subsequent leukemic transformation and survival in myelodysplastic syndrome. Czechoslovak MDS Cooperative Group.

    abstract::240 patients with MDS studied cytogenetically at diagnosis between 1981 and 1990 were followed until death or until April 1992 to evaluate the prognostic significance of FAB classification, age and karyotype. 61 patients (25.4%) subsequently transformed into AML and 176 (73.3%) died during the follow-up period. Patien...

    journal_title:Leukemia research

    pub_type: 杂志文章


    authors: Musilová J,Michalová K,Zemanová Z,Neuwirthová R,Dohnalová A

    更新日期:1995-05-01 00:00:00

  • Maternal and offspring xenobiotic metabolism haplotypes and the risk of childhood acute lymphoblastic leukemia.

    abstract::Discovering genetic predictors of childhood acute lymphoblastic leukemia (ALL) necessitates the evaluation of novel factors including maternal genetic effects, which are a proxy for the intrauterine environment, and robust epidemiologic study designs. Therefore, we evaluated five maternal and offspring xenobiotic meta...

    journal_title:Leukemia research

    pub_type: 临床试验,杂志文章,多中心研究


    authors: Nousome D,Lupo PJ,Okcu MF,Scheurer ME

    更新日期:2013-05-01 00:00:00

  • Correlation between genetic polymorphisms of the hOCT1 and MDR1 genes and the response to imatinib in patients newly diagnosed with chronic-phase chronic myeloid leukemia.

    abstract::The association between seven polymorphisms in the genes hOCT1 and MDR1, encoding for imatinib transporter proteins, and the response to imatinib 400mg/daily was investigated in 65 patients newly diagnosed with chronic-phase chronic myeloid leukemia. The AA genotype at the rs6935207 hOCT1 polymorphic locus was not det...

    journal_title:Leukemia research

    pub_type: 杂志文章


    authors: Maffioli M,Camós M,Gaya A,Hernández-Boluda JC,Alvarez-Larrán A,Domingo A,Granell M,Guillem V,Vallansot R,Costa D,Bellosillo B,Colomer D,Cervantes F

    更新日期:2011-08-01 00:00:00

  • Survival in acute myeloblastic leukemia is not prolonged by remission maintenance or early reinduction chemotherapy. The Toronto Leukemia Study Group.

    abstract::A role for post-induction chemotherapy for adult patients with acute myeloblastic leukemia in remission has not been established. We have studied 125 patients with acute myeloblastic leukemia in complete remission to determine the effect on survival of remission maintenance therapy and of early reinduction therapy giv...

    journal_title:Leukemia research

    pub_type: 临床试验,杂志文章,随机对照试验



    更新日期:1988-01-01 00:00:00

  • Pycnogenol induces differentiation and apoptosis in human promyeloid leukemia HL-60 cells.

    abstract::Pycnogenol, rich of many phytochemicals of medical value, is a commercialized nutrient supplement extracted from the bark of European coastal pine. In this study, we investigated the anti-tumor effects of Pycnogenol on HL-60, U937 and K562 human leukemia cell lines. We found that Pycnogenol inhibited cell proliferatio...

    journal_title:Leukemia research

    pub_type: 杂志文章


    authors: Huang WW,Yang JS,Lin CF,Ho WJ,Lee MR

    更新日期:2005-06-01 00:00:00

  • Prognostic impact of combined NPM1+/FLT3- genotype in patients with acute myeloid leukemia with intermediate risk cytogenetics stratified by age and treatment modalities.

    abstract::The prognostic impact of combined NPM1+/FLT3- genotype is not well defined in elderly patients with acute myeloid leukemia (AML), and in the setting of different treatments, such as cytotoxic chemotherapy (Chemo), hematopoietic cell transplantation (HCT), or hypomethylating agents (HMA). Eighty-two elderly (age >60 ye...

    journal_title:Leukemia research

    pub_type: 杂志文章


    authors: Hefazi M,Siddiqui M,Patnaik M,Wolanskyj A,Alkhateeb H,Zblewski D,Elliott M,Hogan W,Litzow M,Al-Kali A

    更新日期:2015-09-03 00:00:00

  • Effect of pulsed magnetic fields on leukemia-prone AKR mice. No-effect on mortality through five generations.

    abstract::Leukemia-prone AKR mice were exposed twice a week to a 6 mT, 12 Hz or 460 Hz pulsed magnetic field for 30 min. If we take into account the five consecutive generations of mice, the above exposure actually took place in utero and, or during their life span. There was no difference in the incidence of leukemia or in the...

    journal_title:Leukemia research

    pub_type: 杂志文章


    authors: Bellossi A

    更新日期:1991-01-01 00:00:00

  • Src family kinases promote AML cell survival through activation of signal transducers and activators of transcription (STAT).

    abstract::We investigated the role of Src family kinases (SFKs) in the regulation of STAT activation in myeloid leukemia cells. Two of 6 AML cell lines displayed constitutive STAT5 activation, whereas four cell lines had constitutive SFK activity. Treatment with the SFK inhibitors suppressed STAT5 activation and decreased viabi...

    journal_title:Leukemia research

    pub_type: 杂志文章


    authors: Ozawa Y,Williams AH,Estes ML,Matsushita N,Boschelli F,Jove R,List AF

    更新日期:2008-06-01 00:00:00

  • The clinical relevance of IgG subclasses in acute leukemias: low serum IgG as a risk factor for early death due to infection in acute myelogenous leukemia.

    abstract::In order to investigate the clinical significance of IgG subclass levels in adult patients treated for acute lymphocytic (ALL) or myelogenous leukemias (AML), patients were tested before and in regular intervals during and after chemotherapy. Ten patients treated for acute lymphocytic leukemia had normal total IgG and...

    journal_title:Leukemia research

    pub_type: 杂志文章


    authors: Gause A,Schmitz G,von Kalle AK,Lathan B,Diehl V,Pfreundschuh M

    更新日期:1992-01-01 00:00:00

  • Gene mutations in myelodysplasia.

    abstract::The myelodysplastic syndrome is a paradigm of human preleukaemia. Normal haemopoiesis is progressively displaced by an abnormal clone derived from a mutated stem cell. The initial mutation is unknown but its occurrence may be related to the overall load of random mutations which are a consequence of both intrinsic DNA...

    journal_title:Leukemia research

    pub_type: 杂志文章,评审


    authors: Jacobs A

    更新日期:1992-01-01 00:00:00

  • Ricin fusion toxin targeted to the human granulocyte-macrophage colony stimulating factor receptor is selectively toxic to acute myeloid leukemia cells.

    abstract::Treatment failure of patients with acute myelogenous leukemia (AML) is frequently due to the development of multidrug resistance phenotype blasts. We have expressed a fusion protein consisting of human granulocyte-macrophage colony stimulating factor (GMCSF) fused to the N-terminus of a lectin-deficient ricin toxin B ...

    journal_title:Leukemia research

    pub_type: 杂志文章


    authors: Burbage C,Tagge EP,Harris B,Hall P,Fu T,Willingham MC,Frankel AE

    更新日期:1997-07-01 00:00:00

  • Immunologic cell markers of peripheral blood and lymph node lymphocytes in chronic lymphocytic leukemia.

    abstract::The immunologic phenotype of the lymphocytes of 100 patients with chronic lymphocytic leukaemia (CLL) was investigated. Peripheral blood lymphocytes (PBL) were examined in all cases; in 46 patients with lymphadenopathy, a lymph node was biopsied and the histologic and immunologic patterns were assessed: 24 had a lymph...

    journal_title:Leukemia research

    pub_type: 杂志文章


    authors: Resegotti L,Palestro G,Novero D,Micca FB,Godio L,Pistone M,Garnero M,Levis A,Stramignoni A

    更新日期:1987-01-01 00:00:00

  • Analysis of clonality at the level of progenitors in chronic myelogenous leukaemia using the polymerase chain reaction.

    abstract::The Philadelphia (Ph1) chromosome is a specific structural abnormality in which the abl oncogene is activated due to the formation of the novel chimeric gene, bcr/abl. To investigate the clinicopathological role of bcr/abl in Ph1-positive chronic myelogenous leukaemia (CML), we studied the clonal origin of haematopoie...

    journal_title:Leukemia research

    pub_type: 杂志文章


    authors: Sadamura S,Umemura T,Takahira H,Hirata J,Nishimura J,Nawata H

    更新日期:1992-01-01 00:00:00

  • HL-R5 and HL-D4: two differentiation resistant HL-60 variants.

    abstract::A wide range of different agents are capable of inducing the onset of HL-60 differentiation along the myeloid lineage. The diversity of these agents has made the analysis of the molecular mechanisms involved in the regulation of the onset and progress of terminal differentiation in these cells difficult. We have adapt...

    journal_title:Leukemia research

    pub_type: 杂志文章


    authors: Darling DC,Linskens MH,Farzaneh F

    更新日期:1989-01-01 00:00:00

  • Inherited pericentric inversion of chromosome 16 in chronic phase of chronic myeloid leukaemia.

    abstract::The simultaneous occurrence of two specific acquired chromosomal abnormalities in chronic or acute leukaemias is rare. Inherited chromosomal abnormalities are also rare events in the general population. In chronic myeloid leukaemia (CML), characterised by the t(9;22)(q34;q11), the inv(16)(p13q22) has been described as...

    journal_title:Leukemia research

    pub_type: 杂志文章


    authors: Silva PM,Lourenço GJ,Bognone RA,Delamain MT,Pinto-Junior W,Lima CS

    更新日期:2006-01-01 00:00:00

  • Induction of mixed allogeneic chimerism for leukemia.

    abstract::Hybrid (C56BL/6 x DBA) (BDF1; H-2b/H-2d) mice bearing the P815 leukemia (H-2d) were grafted with a (CBA x C57BL/6)F1 (CBF1; H-2k/H-2b) cell suspension, comprising bone marrow cells (BMC; 25 x 10(6)/mouse) and spleen cells (SC; 55 x 10(6)/mouse) on day-4, then treated with cyclophosphamide (200 mg/kg) on day-2 and fina...

    journal_title:Leukemia research

    pub_type: 杂志文章


    authors: Seledtsov VI,Seledtsova GV,Avdeev EV,Samarin DM,Kozlov VA

    更新日期:1997-10-01 00:00:00

  • Achievement of complete molecular responses in late chronic phase chronic myeloid leukaemia patients treated with pulsed imatinib while in minimal residual disease.

    abstract::Chronic myeloid leukaemia (CML) patients in chronic phase (CP) are currently treated with a standard dose of imatinib of 400mg/daily. However, once in complete cytogenetic remission (CCR) it is possible that some patients maintain this status with reduced dose of the drug. Here, we describe five cases of CML in late C...

    journal_title:Leukemia research

    pub_type: 杂志文章


    authors: Breccia M,Cannella L,Stefanizzi C,Santopietro M,De Cuia R,Diverio D,Alimena G

    更新日期:2009-05-01 00:00:00

  • Alteration of intracellular actin levels induced by phorboldiester in human HL-60 leukemia cells susceptible or resistant to differentiation, and the effects of protein kinase inhibitors.

    abstract::During monocyte-macrophage differentiation of HL-60 cells by 12-O-tetradecanoyl phorbol 13-acetate, the intracellular globular(G)-actin and polymerized(F)-actin increased 3-fold and 1.7-fold, respectively. Time course studies showed that these changes of actin levels were nearly coincident with the development of macr...

    journal_title:Leukemia research

    pub_type: 杂志文章


    authors: Uemura Y,Nishikawa M,Komada F,Shirakawa S

    更新日期:1989-01-01 00:00:00