Abstract:
:Selective inhibition of the BCR/ABL tyrosine kinase by imatinib (STI571, Glivec/Gleevec) is the therapeutic strategy in patients with chronic myelogenous leukemia (CML). Despite significant hematologic and cytogenetic responses with imatinib, mainly due to the mutations in the Abl kinase domain, resistance occurs in patients with advanced disease. In the present study on imatinib-resistant K562 cells (IR-K562), however, no such mutations in the Abl kinase domain were observed. Further studies revealed the over-expression of COX-2 and MDR-1 in IR-K562 cells suggesting the possible involvement of COX-2 in the development of resistance to imatinib. So, we sought to examine the effect of celecoxib, a selective COX-2 inhibitor, on IR-K562 cells. The results clearly indicate that celecoxib is more effective in IR-K562 cells with a lower IC50 value of 10 microM compared to an IC50 value of 40 microM in K562 cells. This increase in the sensitivity of IR-K562 cells towards celecoxib suggests that the development of resistance in IR-K562 cells is COX-2 dependent. Further studies revealed down-regulation of MDR-1 by celecoxib and a decline in p-Akt levels. Celecoxib-induced apoptosis of IR-K562 cells led to release of cytochrome c, PARP cleavage and decreased Bcl2/Bax ratio. Also, celecoxib at 1 microM concentration induced apoptosis in IR-K562 cells synergistically with imatinib by reducing the IC50 value of imatinib from 10 to 6 microM. In conclusion, the present study indicates over-expression of COX-2 and MDR-1 in IR-K562 cells and celecoxib, a COX-2 specific inhibitor, induces apoptosis by inhibiting COX-2 and down-regulating MDR-1 expression through Akt/p-Akt signaling pathway.
journal_name
Leuk Resjournal_title
Leukemia researchauthors
Arunasree KM,Roy KR,Anilkumar K,Aparna A,Reddy GV,Reddanna Pdoi
10.1016/j.leukres.2007.11.007subject
Has Abstractpub_date
2008-06-01 00:00:00pages
855-64issue
6eissn
0145-2126issn
1873-5835pii
S0145-2126(07)00439-0journal_volume
32pub_type
杂志文章abstract::Acute promyelocytic leukemia (APL) is highly malignant and frequently expresses the PML-RARalpha (promyelocytic leukemia-retinoic acid receptor-alpha) fusion protein. This fusion protein is targeted by all-trans retinoic acid (ATRA) and arsenic trioxide (As2O3), presently used in APL therapy. We have evaluated effects...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2007.06.021
更新日期:2008-02-01 00:00:00
abstract::The goal of this study was to ascertain the specific effects of 17-N-Allylamino-17-demethoxygeldanamycin (17-AAG) treatment in human acute myelogenous leukemia (AML). Four human leukemia cell lines were treated with varying doses of 17-AAG followed by analysis of toxicity, apoptosis, proliferation, and cell cycle. Cel...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2010.05.024
更新日期:2010-11-01 00:00:00
abstract:BACKGROUND:For most cases of idiopathic acquired sideroblastic anemia (IASA), the molecular pathogenesis is unknown, despite the consistent morphological signature of abundant pathological ringed sideroblasts with their characteristic iron-engorged mitochondria. Moderately elevated free erythrocyte protoporphyrin (FEP)...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2006.06.005
更新日期:2007-05-01 00:00:00
abstract::Homeobox genes HOXA9 and MEIS1 are evolutionarily conserved transcription factors with essential roles in both hematopoiesis and leukemogenesis. They act as dominant cooperating oncoproteins that cause acute leukemias bearing MLL translocations and to a lesser extent T-cell acute lymphocytic leukemia (ALL) characteriz...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2015.04.012
更新日期:2015-08-01 00:00:00
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
更新日期:1987-01-01 00:00:00
abstract::The National Comprehensive Cancer Network (NCCN) defines the following types of acute myeloid leukemia (AML) as favorable-risk: acute promyelocytic leukemia with t(15;17) (APL); AML with core-binding factor (CBF) rearrangements, including t(8;21) and inv(16) or t(16;16) without mutations in KIT (CBF-KITwt); and AML wi...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2017.12.012
更新日期:2018-02-01 00:00:00
abstract::Telomere dysfunction might generate genomic instability leading to the progression of myelodysplastic syndromes (MDS) into acute myeloid leukemia (AML). We investigated telomere length (TL), telomerase activity (TA) and hTERT, c-myc, mad1, and p53 expression in the bone marrow of patients with MDS (n=109), AML (n=47) ...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2013.07.022
更新日期:2013-11-01 00:00:00
abstract::The pre-B lymphoma in SL/Kh mice is a polygenic trait involving a number of host genes. In prelymphoma-stage bone marrow, transient pre-B cell expansion is induced by a host locus, Bomb1, and later followed by the emergence of a monoclonal population with a similar phenotype. To determine whether these pre-B cells rep...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2007.05.013
更新日期:2008-02-01 00:00:00
abstract::We present our first experiences with determination of minimal residual disease (MRD) based on patient specific Flt3-ITD (internal tandem duplication) mutations. We analysed MRD status of 11 AML patients in a retrospective investigation and its potential impact on the follow up of these patients. In five out of six pa...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2004.12.001
更新日期:2005-07-01 00:00:00
abstract::Inosine 5'-monophosphate (IMP) dehydrogenase catalyzes the rate-limiting reaction of guanine nucleotide biosynthesis and has been implicated in the reaction of cell growth and differentiation. We investigated the ability of mycophenolate mofetil, a prodrug of mycophenolic acid, to induce differentiation in HL-60 and U...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/s0145-2126(00)00045-x
更新日期:2000-09-01 00:00:00
abstract::We report on our experience relating to 62 patients with myelodysplastic syndrome (MDS) aged less than 50 years, seen at our Institution and conservatively treated from July 1983 to December 2000. Patients demographics and clinical features at diagnosis were analysed for their prognostic value on survival and on risk ...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2005.01.003
更新日期:2005-07-01 00:00:00
abstract::Thermal stress induces expression of a family of heat shock proteins which may regulate the synthesis of various cellular genes. We investigated the effect of heat shock on polyadenylation in Epstein-Barr Virus (EBV) negative and EBV transformed human Burkitt's lymphoma (BL) B-cell lines. Incubation of the BL B-cell l...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(95)00063-1
更新日期:1995-11-01 00:00:00
abstract::Microtubular reorganisation contributing to apoptotic morphology occurs in normal and neoplastic cells undergoing apoptosis induced by cytotoxic drugs [1-3]. The aim of this study was to correlate the changes in the microtubules (MTs) with behavior of the centrosome in apoptotic cells, and to see whether post-translat...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/s0145-2126(97)00038-6
更新日期:1997-06-01 00:00:00
abstract::The role of hemin induction of K562 in inositol phospholipid metabolism has not been previously studied. K562 cells were induced to synthesize hemoglobin upon addition of bovine hemin to the culture media. The phospholipid content of K562 was determined before and after the addition of hemin. The results of this study...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(91)90055-x
更新日期:1991-01-01 00:00:00
abstract::Compound 48 (C48) is a novel dual ligand for peroxisome proliferator-activated receptor alpha and gamma (PPAR alpha/gamma). Culture of imatinib-sensitive and -resistant CML cell lines with C48 resulted in a strong growth inhibition which associated with G0/G1 cell cycle arrest. However, it showed no obvious toxicity t...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2008.11.023
更新日期:2009-05-01 00:00:00
abstract::In a prospective study of 27 patients with acute myeloid leukaemia (AML) quality of life was studied using three different instruments, Life Ingredient Profile, Karnofsky Performance Scale and Vitagram. The course of the disease was followed during the induction period, remission, relapse and in the terminal phase. We...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(94)90028-0
更新日期:1994-04-01 00:00:00
abstract::The PRAME gene encodes an antigen recognized by autologous T lymphocytes and is expressed in trophoblasts, testis and frequently in human solid cancers and acute leukemias, making it a candidate for immunotherapy and for detecting MRD. We demonstrate expression of PRAME by RT-PCR in the peripheral blood or bone marrow...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/s0145-2126(02)00217-5
更新日期:2003-05-01 00:00:00
abstract::AML progenitor cells (AML-PC) undergo significant apoptosis in response to the deacetylase inhibitor (DACi) LAQ824 and lose the replating capacity which was not observed with the DACi valproic acid. Treatment of normal hematopoietic progenitor cells (HPC) with LAQ824 resulted in (i) inhibition of differentiation, (ii)...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2010.06.024
更新日期:2011-01-01 00:00:00
abstract::MDS is primarily a disease of the elderly. Cases who give a history of exposure to X-rays, cytotoxic drugs or leukaemogenic chemicals may be younger. Many cases of MDS present because of an incidental blood count. The most prominent clinical features are those of anaemia, neutropenia, thrombocytopenia. Because haemopo...
journal_title:Leukemia research
pub_type: 杂志文章,评审
doi:10.1016/0145-2126(92)90106-h
更新日期:1992-01-01 00:00:00
abstract::The surface marker phenotype of lymphocytes derived from 12 patients with B-CLL was compared to that of lymphocytes from 10 patients with an other monoclonal but clinical benign form of B-cell proliferative disorder termed monoclonal B-cell lymphocytosis of undetermined significance (B-MLUS). A panel of well character...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(89)90028-3
更新日期:1989-01-01 00:00:00
abstract::It has been suggested that imatinib mesylate (IM) influences osteogenesis and bone turnover in treated patients. Here we show that the inhibitory effect of IM on cell multiplication is associated with an increased proportion of spliced osteocalcin (OCNs) in leukemia (HL-60) and osteosarcoma cells (MG-63, U-2 OS), desp...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2007.07.020
更新日期:2008-03-01 00:00:00
abstract::CFW/D mice injected neonatally with a type B retrovirus, (DMBA-LV), rapidly develop thymic lymphomas. The present study examined simultaneously the karyotype and the expression of surface antigens on thymocytes from DMBA-LV treated mice at 28, 35 and 42 days of age during the development of lymphomas, and of cells fro...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(89)90122-7
更新日期:1989-01-01 00:00:00
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
doi:10.1016/j.leukres.2017.06.010
更新日期:2017-09-01 00:00:00
abstract::We investigated the therapeutic activity of recombinant erythropoietin (r-EPO) in association with thalidomide in 30 patients with myelodysplastic syndromes (MDS), previously treated with r-EPO (n.15, group A) or thalidomide (n.15, group B) as single agents, respectively, without any significant benefit on their anemi...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2005.08.020
更新日期:2006-04-01 00:00:00
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
更新日期:1996-08-01 00:00:00
abstract::DNAs from chronic granulocytic leukaemia (CGL) and chronic myelomonocytic leukaemia (CMML) were assayed for transforming genes by transfection into NIH 3T3 cells. Foci DNA was tagged with a geneticin-resistance cosmid, then followed through a drug selection and tumorigenicity assay. Activated Ha-ras genes, with point ...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(88)90033-1
更新日期:1988-01-01 00:00:00
abstract::The inaugural meeting of the International Working Group on MDS cytogenetics convened 22-23 October 2007 in Chicago, IL. Under the sponsorship of the Myelodysplastic Syndromes Foundation, the group was organized to address the substantial need for worldwide standardized cytogenetic testing for MDS in clinical practice...
journal_title:Leukemia research
pub_type: 总体
doi:10.1016/j.leukres.2008.03.009
更新日期:2008-09-01 00:00:00
abstract::Allogeneic hematopoietic stem cell transplantation provides curative therapy for some patients with advanced hematologic malignancies. Disease response after allogeneic transplant is, at least in part, mediated by donor immune cells. In this report we describe a cellular therapy using haploidentical peripheral blood s...
journal_title:Leukemia research
pub_type: 临床试验,杂志文章
doi:10.1016/j.leukres.2008.05.015
更新日期:2008-12-01 00:00:00
abstract::This study examined the immunoregulatory role of recombinant interleukin 4 (IL-4), also known as B-cell stimulating factor 1, on the generation of cytotoxic effector cells from normal and leukaemic human blood mononuclear cells. When tested on cells from normal individuals, the addition of IL-4 to mixed lymphocyte cul...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(89)90066-0
更新日期:1989-01-01 00:00:00
abstract::We hypothesized that the high early death rate (EDR) due to bleeding in acute promyelocytic leukemia (APL) is in part attributable to delays in all- trans retinoic acid (ATRA). We conducted a retrospective analysis of the timing of ATRA administration. 204 consecutive patients with newly diagnosed APL between 1992 and...
journal_title:Leukemia research
pub_type: 杂志文章,多中心研究
doi:10.1016/j.leukres.2013.05.007
更新日期:2013-09-01 00:00:00