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 chain (RTB) in Spodoptera frugiperda insect cells. The fusion protein was purified by immunoaffinity chromatography and reassociated with chemically deglycosylated ricin toxin A chain (RTA). The resulting fusion toxin was found to react with antibodies to GMCSF, RTB and RTA and had the predicted molecular mass of 80 kDa. GMCSF-ricin bound poorly to asialofetuin (Kd = 10(6) M-1) and receptor negative cells indicating loss of lectin activity, but bound strongly to GMCSF receptor positive HL60 cells. Ligand displacement assays showed fusion toxin affinity 2.6-fold less than native GMCSF. Selective inhibition of protein synthesis was observed on receptor positive cells. Induction of apoptosis was also observed on receptor positive cells. Cells expressing multidrug resistance gene products (P-gp, Bcl2 and BclXL) were also sensitive to fusion toxin. These results suggest that GMCSF-ricin deserves further preclinical development.

journal_name

Leuk Res

journal_title

Leukemia research

authors

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

doi

10.1016/s0145-2126(97)00043-x

subject

Has Abstract

pub_date

1997-07-01 00:00:00

pages

681-90

issue

7

eissn

0145-2126

issn

1873-5835

pii

S014521269700043X

journal_volume

21

pub_type

杂志文章
  • Distinct cellular origins of primary effusion lymphoma with and without EBV infection.

    abstract::Kaposi's sarcoma-associated herpesvirus (KSHV) is associated with three distinct lymphoproliferative disorders: primary effusion lymphoma (PEL), multicentric Castleman's disease (MCD) and germinotropic lymphoproliferative disorder (GLD). KSHV positive lymphocytes in GLD and in most cases of PEL are co-infected by Epst...

    journal_title:Leukemia research

    pub_type: 杂志文章

    doi:10.1016/j.leukres.2003.08.003

    authors: Hamoudi R,Diss TC,Oksenhendler E,Pan L,Carbone A,Ascoli V,Boshoff C,Isaacson P,Du MQ

    更新日期:2004-04-01 00:00:00

  • Synergism between clofarabine and decitabine through p53R2: a pharmacodynamic drug-drug interaction modeling.

    abstract::Clofarabine (CLO), a purine nucleoside analog with promising efficacy in acute myeloid leukemia (AML), inhibits the ribonucleotidereductase, p53R2. We have shown that p53R2 mRNA is up-regulated by decitabine (DEC), another drug with promising activity in AML. We developed a pharmacodynamic model to characterize the in...

    journal_title:Leukemia research

    pub_type: 杂志文章

    doi:10.1016/j.leukres.2012.07.015

    authors: Thudium KE,Ghoshal S,Fetterly GJ,Haese JP,Karpf AR,Wetzler M

    更新日期:2012-11-01 00:00:00

  • Regular analgesic use and risk of multiple myeloma.

    abstract::Analgesic use has been implicated in the chemoprevention of a number of solid tumors, but to date no previous research has focused on the role of analgesics in the etiology of multiple myeloma (MM). We conducted a hospital-based case-control study of 117 patients with primary, incident MM and 483 age and residence mat...

    journal_title:Leukemia research

    pub_type: 杂志文章,随机对照试验

    doi:10.1016/j.leukres.2006.07.027

    authors: Moysich KB,Bonner MR,Beehler GP,Marshall JR,Menezes RJ,Baker JA,Weiss JR,Chanan-Khan A

    更新日期:2007-04-01 00:00:00

  • Acute myeloid leukemia with 11q23 rearrangements: A study of therapy-related disease and therapeutic outcomes.

    abstract::We described the clinical features and outcomes for 63 adult patients with acute myeloid leukemia (AML) with a translocation involving the 11q23 locus (MLL) who were treated at Memorial Sloan Kettering Cancer Center (MSK). The population included 40 female (63 %) and 23 male (37 %) patients, with a median age of 51 ye...

    journal_title:Leukemia research

    pub_type: 杂志文章

    doi:10.1016/j.leukres.2020.106453

    authors: Menghrajani K,Zhang Y,Famulare C,Devlin SM,Tallman MS

    更新日期:2020-11-01 00:00:00

  • Partial restoration of all trans retinoic acid (ATRA) sensitivity by compactin in ATRA-resistant leukemic cells (ATRA-R HL-60).

    abstract::The resistance to all trans retinoic acid (ATRA) differentiating treatment is a consequence, in most of the cases, of either increased catabolism or down regulation of ATRA uptake. Recently, we have shown that ATRA efficiency to differentiate HL-60 cells was enhanced about 30 times after its incorporation into Low Den...

    journal_title:Leukemia research

    pub_type: 杂志文章

    doi:10.1016/s0145-2126(00)00019-9

    authors: Gueddari N,Madoulet C,Lefebvre P,Berthou L,Chomienne C,Jardillier JC

    更新日期:2000-06-01 00:00:00

  • All-trans and 9-cis retinoic acid enhance 1,25-dihydroxyvitamin D3-induced monocytic differentiation of U937 cells.

    abstract::Retinoic acid (RA) and 1,25-dihydroxyvitamin D3 (D3) are well known for inducing differentiation in many leukemic cell lines. The nuclear signalling pathways of RA and D3 are mediated through their cognate receptors, the retinoic acid receptor (RAR) and vitamin D3 receptor (VDR), respectively. Retinoid X receptor (RXR...

    journal_title:Leukemia research

    pub_type: 杂志文章

    doi:10.1016/0145-2126(96)00020-3

    authors: Nakajima H,Kizaki M,Ueno H,Muto A,Takayama N,Matsushita H,Sonoda A,Ikeda Y

    更新日期:1996-08-01 00:00:00

  • Dequalinium induces cytotoxicity in human leukemia NB4 cells by downregulation of Raf/MEK/ERK and PI3K/Akt signaling pathways and potentiation of specific inhibitors of these pathways.

    abstract::Delocalized lipophilic cation dequalinium (DQA) selectively accumulates in mitochondria and displays anticancer activity in different malignancies. Our previous studies indicate a DQA-induced cytotoxicity in human acute promyelocytic leukemia NB4 cells by early disturbance in mitochondrial function and oxidative stres...

    journal_title:Leukemia research

    pub_type: 杂志文章

    doi:10.1016/j.leukres.2014.01.009

    authors: García-Pérez AI,Galeano E,Nieto E,Estañ MC,Sancho P

    更新日期:2014-07-01 00:00:00

  • A role for mitochondrial DNA in the pathogenesis of radiation-induced myelodysplasia and secondary leukemia.

    abstract::The onset of acute myeloid leukemia following ionizing radiation or alkylating agent exposure is antedated months to years by the development of 'preleukemia', or secondary myelodysplastic syndrome (sMDS). Mitochondrial abnormalities induced by chloramphenicol and clonal deletions of mitochondrial DNA (mt DNA) in the ...

    journal_title:Leukemia research

    pub_type: 杂志文章,评审

    doi:10.1016/0145-2126(93)90036-k

    authors: Hatfill SJ,La Cock CJ,Laubscher R,Downing TG,Kirby R

    更新日期:1993-11-01 00:00:00

  • Expression of functional markers in acute lymphoblastic leukemia.

    abstract::We analyzed surface antigens, multidrug resistance (MDR) parameters (PGP, MRP, LRP), tissue infiltration parameters (CD18, CD44, VCAM, MMP2), receptors for colony stimulating factors (G-CSFr, GM-CSFr) and cell cycle parameters (Ki-67, topoisomerase IIalpha) in 86 patients with acute lymphoblastic leukemia (ALL). LRP, ...

    journal_title:Leukemia research

    pub_type: 杂志文章

    doi:10.1016/s0145-2126(03)00026-2

    authors: Oh EJ,Kahng J,Kim Y,Kim M,Lim J,Kang CS,Min WS,Cho B,Lee A,Lee KY,Kim WI,Shim SI,Han K

    更新日期:2003-10-01 00:00:00

  • Terminal deoxynucleotidyl transferase (TdT)-containing peripheral blood mononuclear cells during remission of acute lymphoblastic leukemia: low sensitivity and specificity prevent accurate prediction of relapse.

    abstract::Serial samples of peripheral blood were obtained from 75 children with acute lymphoblastic leukemia in remission. An immunofluorescence assay was used to quantitate TdT-containing (terminal deoxynucleotidyl transferase-containing) cells in the mononuclear leukocyte fraction of these specimens. Nine relapses in 8 patie...

    journal_title:Leukemia research

    pub_type: 杂志文章

    doi:10.1016/0145-2126(87)90089-0

    authors: Hetherington ML,Huntsman PR,Smith RG,Buchanan GR

    更新日期:1987-01-01 00:00:00

  • Metachronous and synchronous presentation of acute myeloid leukemia and lung cancer.

    abstract::Smoking is associated with both acute myeloid leukemia (AML) and lung cancer. We therefore searched our database for concomitant presentation of AML and lung cancer. Among 775 AML cases and 5225 lung cancer cases presenting to Roswell Park Cancer Institute between the years January 1992 and May 2008 we found 12 (1.5% ...

    journal_title:Leukemia research

    pub_type: 杂志文章

    doi:10.1016/j.leukres.2008.12.016

    authors: Varadarajan R,Ford L,Sait SN,Block AW,Barcos M,Wallace PK,Ramnath N,Wang ES,Wetzler M

    更新日期:2009-09-01 00:00:00

  • Autologous bone marrow transplantation in acute myeloid leukemia after in-vitro purging with an anti-lacto-N-fucopentaose III antibody and rabbit complement.

    abstract::Two AML patients, whose leukemic clonogenic cells totally reacted to the anti-lactofucopentaose III S4-7 monoclonal antibody (MoAb), underwent autologous bone marrow transplantation, in first complete remission, after in-vitro purging with S4-7 MoAb and complement. After ablative chemotherapy (BAVC regimen) and reinfu...

    journal_title:Leukemia research

    pub_type: 杂志文章

    doi:10.1016/0145-2126(87)90050-6

    authors: Ferrero D,De Fabritiis P,Amadori S,De Felice L,Gallo E,Meloni G,Pregno P,Pulsoni A,Simone F,Tarella C

    更新日期:1987-01-01 00:00:00

  • Identification of a novel, tissue-specific ABCG2 promoter expressed in pediatric acute megakaryoblastic leukemia.

    abstract::ABCG2 encodes a transporter protein that is associated with multidrug-resistant phenotypes in many cancers, including acute myeloid leukemia (AML); high levels of expression are generally associated with a poor prognosis. To better understand how expression of ABCG2 is controlled in pediatric AML, we performed a detai...

    journal_title:Leukemia research

    pub_type: 杂志文章

    doi:10.1016/j.leukres.2011.05.004

    authors: Campbell PK,Zong Y,Yang S,Zhou S,Rubnitz JE,Sorrentino BP

    更新日期:2011-10-01 00:00:00

  • PD-1/PD-L1 expression in extra-medullary lesions of multiple myeloma.

    abstract::Multiple myeloma patients may develop extraosseous involvement in the course of the disease making prognosis very poor and new drugs clearly needed. The PD-1/PD-L1 axis has emerged as a master immune checkpoint in antitumor responses and recent studies investigated the role of PD-L1 in multiple myeloma cells; no data ...

    journal_title:Leukemia research

    pub_type: 杂志文章

    doi:10.1016/j.leukres.2016.09.008

    authors: Crescenzi A,Annibali O,Bianchi A,Pagano A,Donati M,Grifoni A,Avvisati G

    更新日期:2016-10-01 00:00:00

  • Long-term bone marrow culture-derived stromal fibroblasts as a potential target for gene therapy in acute myelogenous leukemia.

    abstract::As a part of our continuing efforts to develop gene therapy for acute myelogenous leukemia (AML), this study was undertaken to evaluate the possibility of using autologous bone marrow stromal fibroblasts (BMSFs) as a target cell population. Autologous BMSFs in AML were isolated from the stromal layers of long-term bon...

    journal_title:Leukemia research

    pub_type: 杂志文章

    doi:10.1016/s0145-2126(01)00134-5

    authors: Min YH,Li GX,Jang JH,Suh HC,Kim JS,Cheong JW,Lee ST,Hahn JS,Ko YW

    更新日期:2002-04-01 00:00:00

  • High Th1/Th2 ratio in patients with multiple myeloma.

    abstract::To determine the clinical significance of the T helper 1(Th1)/T helper 2 (Th2) ratio in multiple myeloma, the intracellular IFN-gamma and IL-4 were analyzed by flow cytometry in 56 patients with multiple myeloma. The mean Th1/Th2 ratio of cases in the initial diagnosis phase and the refractory phase were higher than t...

    journal_title:Leukemia research

    pub_type: 杂志文章

    doi:10.1016/j.leukres.2004.06.003

    authors: Ogawara H,Handa H,Yamazaki T,Toda T,Yoshida K,Nishimoto N,Al-ma'Quol WH,Kaneko Y,Matsushima T,Tsukamoto N,Nojima Y,Matsumoto M,Sawamura M,Murakami H

    更新日期:2005-02-01 00:00:00

  • Ubiquitin-proteasome system profiling in acute leukemias and its clinical relevance.

    abstract::The ubiquitin-proteasome system (UPS) plays a major role in the homeostasis of cellular protein. We demonstrate that each of the major hematologic diseases (AML, ALL, and MDS) has a specific and different plasma profile of UPS protein and enzymatic activities. While high levels of proteasome and ubiquitin proteins and...

    journal_title:Leukemia research

    pub_type: 杂志文章

    doi:10.1016/j.leukres.2010.09.009

    authors: Ma W,Kantarjian H,Zhang X,Wang X,Estrov Z,O'Brien S,Albitar M

    更新日期:2011-04-01 00:00:00

  • Analysis of T-cell receptor-γ gene rearrangements using heteroduplex analysis by high-resolution microcapillary electrophoresis.

    abstract::Determination of T-cell clonality has an important additional value for diagnosis of T-cell lymphomas. Various molecular methods have been developed, including polymerase chain reaction (PCR) of T-cell receptor γ (TCRγ). The detection of PCR products usually relies commonly on either GeneScan (GS) analysis or heterodu...

    journal_title:Leukemia research

    pub_type: 杂志文章

    doi:10.1016/j.leukres.2012.06.003

    authors: Beaufils N,Ben Lassoued A,Essaydi A,Dales JP,Formisano-Tréziny C,Bonnet N,Grob JJ,Gabert J

    更新日期:2012-09-01 00:00:00

  • Effects of interleukin 2 on engraftment following autologous bone marrow transplantation (ABMT) in dogs.

    abstract::Beagle dogs were treated with recombinant human interleukin 2 (IL-2) 6 x 10(6) International Units (IU)/day for 7 consecutive days following conditioning with sublethal (200 cGy) or lethal (400 cGy) doses of high-dose rate whole body irradiation (WBI) and reconstitution with 2 x 10(8)/kg autologous bone marrow cells, ...

    journal_title:Leukemia research

    pub_type: 杂志文章

    doi:10.1016/0145-2126(92)90075-i

    authors: Samuel S,Nagler A,Or R,Slavin S

    更新日期:1992-10-01 00:00:00

  • Karyotypic findings as an independent prognostic marker in chronic myeloid leukaemia blast crisis.

    abstract::Fifty-three patients with Ph positive chronic myeloid leukaemia in blastic phase were studied. Additional abnormalities were found in 29 (55%) patients and were more common in myeloid (64%) than lymphoid (45%) blast crisis. The most frequent were +Ph (32%), +8 (28%), +19 (19%), +20 (9%) and +21 (9%). i(17q) (9%) was a...

    journal_title:Leukemia research

    pub_type: 杂志文章

    doi:10.1016/0145-2126(94)90023-x

    authors: Nanjangud G,Kadam PR,Saikia T,Bhisey AN,Kumar A,Gopal R,Chopra H,Nair CN,Advani SH

    更新日期:1994-05-01 00:00:00

  • Molecular modification of a recombinant, bivalent anti-human CD3 immunotoxin (Bic3) results in reduced in vivo toxicity in mice.

    abstract::A novel bivalent single chain fusion protein, Bic3, was assembled consisting of the catalytic and translocation domains of diphtheria toxin (DT(390)) fused to two repeating sFv molecules recognizing human CD3 epsilon of the human T-cell receptor. Historically, problems with these constructs include low yield, toxicity...

    journal_title:Leukemia research

    pub_type: 杂志文章

    doi:10.1016/j.leukres.2004.08.006

    authors: Vallera DA,Todhunter D,Kuroki DW,Shu Y,Sicheneder A,Panoskaltsis-Mortari A,Vallera VD,Chen H

    更新日期:2005-03-01 00:00:00

  • Expression pattern of the septin gene family in acute myeloid leukemias with and without MLL-SEPT fusion genes.

    abstract::Septins are proteins associated with crucial steps in cell division and cellular integrity. In humans, 14 septin genes have been identified, of which five (SEPT2, SEPT5, SEPT6, SEPT9, and SEPT11) are known to participate in reciprocal translocations with the MLL gene in myeloid neoplasias. We have recently shown a sig...

    journal_title:Leukemia research

    pub_type: 杂志文章

    doi:10.1016/j.leukres.2009.08.018

    authors: Santos J,Cerveira N,Bizarro S,Ribeiro FR,Correia C,Torres L,Lisboa S,Vieira J,Mariz JM,Norton L,Snijder S,Mellink CH,Buijs A,Shih LY,Strehl S,Micci F,Heim S,Teixeira MR

    更新日期:2010-05-01 00:00:00

  • The incidence of hybrid acute leukaemias.

    abstract::During a 4-yr period, 292 patients with acute leukaemia were studied using morphology, cytochemistry and immunologic reagents to determine the cell lineage of the leukaemia. One hundred and sixty-three cases were shown to be acute lymphoblastic leukaemia (ALL), 127 acute myeloblastic leukaemia (AML) and two cases (0.6...

    journal_title:Leukemia research

    pub_type: 杂志文章

    doi:10.1016/0145-2126(88)90002-1

    authors: Ruiz-Argüelles GJ,Lobato-Mendizábal E,Marín-López A

    更新日期:1988-01-01 00:00:00

  • Detection of t(14;18) in turkish follicular lymphomas using the polymerase chain reaction.

    abstract::A t(14;18) translocation is closely associated with the follicular lymphoma but is also seen in diffuse B cell lymphomas with a previous history of a follicular lymphoma as well as de novo diffuse lymphomas. Estimation of the frequency of t(14;18) in follicular lymphoma vary widely from 33 to 89%. Furthermore, no exte...

    journal_title:Leukemia research

    pub_type: 杂志文章

    doi:10.1016/s0145-2126(00)00009-6

    authors: Sayhan N,Tuzuner N,Aki H,Demir G,Berkarda B

    更新日期:2000-06-01 00:00:00

  • Combined effects of interferon and steroid hormones on 2',5'-oligoadenylate synthetase activity in chronic lymphocytic leukemia cells.

    abstract::2',5'-oligoadenylate synthetase (OAS) has been implicated in the effects of interferons (INF) and steroid hormones on cell growth and differentiation. We studied the combined effects in vitro of hormones and INF on OAS activity in cells from 10 patients with chronic lymphocytic leukemia. IFN enhanced OAS activity in a...

    journal_title:Leukemia research

    pub_type: 杂志文章

    doi:10.1016/0145-2126(89)90163-x

    authors: Triozzi PL,Avery KB,Abou-Issa HM,Chou TC

    更新日期:1989-01-01 00:00:00

  • Reciprocal alterations of GMP reductase and IMP dehydrogenase activities during differentiation in HL-60 leukemia cells.

    abstract::The study was undertaken to elucidate the regulatory roles of GMP reductase (GMPR) and IMP dehydrogenase (IMPDH) on purine interconversion during differentiation. Treatment of HL-60 cells with retinoic acid (1 microM) induced granulocytic differentiation which was accompanied with a 2.4-fold increase in GMPR and 55% d...

    journal_title:Leukemia research

    pub_type: 杂志文章

    doi:10.1016/0145-2126(92)90002-o

    authors: Nakamura H,Natsumeda Y,Nagai M,Takahara J,Irino S,Weber G

    更新日期:1992-06-01 00:00:00

  • Intensive chemotherapy of poor prognosis myelodysplastic syndromes (MDS) and acute myeloid leukemia following MDS with idarubicin and cytarabine.

    abstract::Forty patients with high risk myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) preceded by MDS were treated with intensive induction and consolidation chemotherapy in a prospective multicenter pilot study. They were given two cycles of cytarabine 100 mg/m with 12-h intervals on days 1-7 and idarubicin 12...

    journal_title:Leukemia research

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1016/s0145-2126(96)00116-6

    authors: Ruutu T,Hänninen A,Järventie G,Koistinen P,Koivunen E,Kätkä K,Nousiainen T,Oksanen K,Pelliniemi TT,Remes K,Timonen T,Volin L,Elonen E

    更新日期:1997-02-01 00:00:00

  • Aberrant promotor methylation in MDS hematopoietic cells during in vitro lineage specific differentiation is differently associated with DNMT isoforms.

    abstract::Aberrant promoter methylation may contribute to the hematopoietic disturbances in myelodysplastic syndromes (MDS). To explore a possible mechanism, we therefore analyzed expression of DNA methyltransferase (DNMT) subtypes kinetics and aberrant promoter methylation of key regulatory genes during MDS hematopoiesis. An i...

    journal_title:Leukemia research

    pub_type: 杂志文章

    doi:10.1016/j.leukres.2008.08.014

    authors: Hopfer O,Komor M,Koehler IS,Freitag C,Schulze M,Hoelzer D,Thiel E,Hofmann WK

    更新日期:2009-03-01 00:00:00

  • Ploidy status rarely changes in myeloma patients at disease progression.

    abstract::Hyperdiploid and non-hyperdiploid multiple myeloma represents distinct biological entities characterized by different patterns of genetic changes. We sought to determine whether ploidy category (non-hyperdiploid versus hyperdiploid) remains stable over time from diagnosis to progression. Of the 43 patients studied (39...

    journal_title:Leukemia research

    pub_type: 临床试验,杂志文章

    doi:10.1016/j.leukres.2005.07.004

    authors: Chng WJ,Winkler JM,Greipp PR,Jalal SM,Bergsagel PL,Chesi M,Trendle MC,Ahmann GJ,Henderson K,Blood E,Oken MM,Hulbert A,Van Wier SA,Santana-Dávila R,Kyle RA,Gertz MA,Lacy MQ,Dispenzieri A,Fonseca R

    更新日期:2006-03-01 00:00:00

  • Nilotinib post-liver transplantation for acute hepatic failure related to imatinib.

    abstract::This is the case report of a 47-year-old woman referred to our institution due to acute liver failure related to imatinib, who was submitted to a successful liver transplantation. Nilotinib was safely used post-transplant. ...

    journal_title:Leukemia research

    pub_type: 信件

    doi:10.1016/j.leukres.2009.06.012

    authors: Perini GF,Santos FP,Funke V,Ruiz J,Neto BH,Hamerschlak N

    更新日期:2009-12-01 00:00:00