Abstract：
:Imatinib is a highly effective drug for the treatment of chronic myeloid leukemia (CML) that targets the BCR-ABL kinase. However, a number of patients have CML that is resistant to Imatinib treatment. In this report, we developed AGM130 as a potential therapeutic drug for Imatinib-resistant CML treatment. The AGM130 compound is derived from Indirubin, which is an ingredient of Danggui Longhui Wan and known as a cyclin-dependent kinase (CDK) inhibitor. The water solubility of AGM130 is more enhanced than that of the original form of Indirubin, which has very poor water solubility. Our data showed that the AGM130 compound efficiently decreased the viability of CML-derived K562 cells. Moreover, this compound also efficiently decreased the viability of Imatinib-resistant K562 cells in in vitro and in vivo systems. In addition, like Indirubin, AGM130 also inhibited phosphorylation of retinoblastoma protein (Rb), which is a major substrate of CDK. Conclusively, our data suggest that AGM130 is a strong candidate for treating Imatinib-resistant CML.
journal_name
Leuk Resjournal_title
Leukemia researchauthors
Kim WS,Lee MJ,Kim DH,Lee JE,Kim JI,Kim YC,Song MR,Park SGdoi
10.1016/j.leukres.2012.12.017subject
Has Abstractpub_date
2013-04-01 00:00:00pages
427-33issue
4eissn
0145-2126issn
1873-5835pii
S0145-2126(12)00502-4journal_volume
37pub_type
杂志文章abstract：:We designed a pharmacokinetic and pharmacodynamic phase I study of sequential topotecan (2.55-6.3mg/m2) by 72h infusion followed by five daily doses of etoposide for patients with refractory acute leukemia based upon synergistic anti-tumor activity of topoisomerase I and II inhibitors in vitro. Eight of the 29 patient...
journal_title：Leukemia research
pub_type： 临床试验,杂志文章
doi：10.1016/s0145-2126(02)00079-6
更新日期：2003-01-01 00:00:00
abstract：:A primary mitochondrial defect may be pivotal in the pathogenesis of acquired idiopathic sideroblastic anemia (AISA). The mitochondrial respiratory chain is involved in mitochondrial iron uptake and supply of ferrous iron (Fe2+) for heme synthesis. Mitochondrial DNA (mtDNA) comes into play because several subunits of ...
journal_title：Leukemia research
pub_type： 杂志文章,评审
doi：10.1016/s0145-2126(99)00160-5
更新日期：2000-02-01 00:00:00
abstract：:Although verapamil, cyclosporin A. cremophor EL and PSC-833 are active as multidrug resistance modulators, there has been limited study of these compounds as possible chemotherapy enhancing agents against drug-sensitive tumors. We compared these agents as modifiers of VP-16 cytotoxicity in vitro and modifiers of VP-16...
journal_title：Leukemia research
pub_type： 杂志文章
doi：10.1016/0145-2126(95)00029-n
更新日期：1995-08-01 00:00:00
abstract：:The classical myeloproliferative neoplasms (MPN) are comparatively uncommon in children and display a degree of mutational naivety if considering the high frequency of known MPN driver events observed in the corresponding adult diseases. Whole exome sequencing has unravelled much of the underlying molecular complexity...
journal_title：Leukemia research
pub_type： 信件
doi：10.1016/j.leukres.2014.06.003
更新日期：2014-08-01 00:00:00
abstract：:The capacity of human thymocytes and of differentiated lymphocytes circulating in peripheral blood to perform unscheduled DNA synthesis (a measure of nucleotide excision repair) after UV irradiation was measured by radioautographic analysis. Only 4% of immature T lymphocytes, but 68% of circulating lymphocytes exhibit...
journal_title：Leukemia research
pub_type： 杂志文章
doi：10.1016/0145-2126(85)90006-2
更新日期：1985-01-01 00:00:00
abstract：:Proto-oncogene transcriptional activation was analyzed in a group of MCF 247 MuLv-induced T-cell lymphomas to identify transformation-specific gene activations and determine whether the proviral insertion near a myc gene could promote a peculiar mechanism of transformation through a differential proto-oncogene express...
journal_title：Leukemia research
pub_type： 杂志文章
doi：10.1016/0145-2126(90)90007-v
更新日期：1990-01-01 00:00:00
abstract：:C3H/He mice produce myeloid leukemias after whole body irradiation of 1-3Gy as compared with non-irradiated controls that produce fewer than 1% of leukemia [Radiatiton Research 127 (1991) 146]. Thus, p53-deficient C57BL/6 strain, a malignant lymphoma prone, was crossed back into C3H/He strain. Lethally irradiated wild...
journal_title：Leukemia research
pub_type： 杂志文章
doi：10.1016/s0145-2126(02)00032-2
更新日期：2002-12-01 00:00:00
abstract：:MONO-MAC-1 is a human cell line with properties of blood monocytes, which can be used as a model system to study monocytic functions in vitro. In the present study, we prepared a karyotype of MONO-MAC-1, analysed the growth behaviour, determined the presence of differentiation-associated antigens and studied the expre...
journal_title：Leukemia research
pub_type： 杂志文章
doi：10.1016/s0145-2126(96)00129-4
更新日期：1997-04-01 00:00:00
abstract：:A permanent cell line, MN 60, was established from the peripheral blood of a patient with an acute lymphoblastic leukemia (ALL) classified morphologically as being of the L3 type. Cell growth started rapidly in vitro and no feeder cells were needed. Cells of the MN-60 line were identical to the original leukemic cells...
journal_title：Leukemia research
pub_type： 杂志文章
doi：10.1016/0145-2126(82)90085-6
更新日期：1982-01-01 00:00:00
abstract：:Bone marrow cells of five patients with acute myeloid leukemia were fractionated by means of counterflow centrifugation (elutriation). The different fractions were enriched with cells belonging to subsequent stages of the cell cycle. Cytokinetic evaluation of these cell fractions was performed by [3H]thymidine autorad...
journal_title：Leukemia research
pub_type： 杂志文章
doi：10.1016/0145-2126(82)90031-5
更新日期：1982-01-01 00:00:00
abstract：:The functional behavior of hematopoietic stem cell (HSC) and progenitors in chronic myelomonocytic leukemia (CMML) and on disease progression is little known. We performed cell proliferation, apoptosis, hematopoietic colony forming/replating and differentiation potential studies in the purified subpopulations of Lin(-...
journal_title：Leukemia research
pub_type： 杂志文章
doi：10.1016/j.leukres.2008.02.011
更新日期：2008-09-01 00:00:00
abstract：:Vinorelbine chemotherapy with G-CSF stimulation is the standard mobilization regimen in Switzerland for multiple myeloma patients. However, with the increasing use of bortezomib during induction treatment, adding the neurotoxic compound vinorelbine for mobilization may aggravate bortezomib-induced polyneuropathy. In t...
journal_title：Leukemia research
pub_type： 杂志文章
doi：10.1016/j.leukres.2015.03.015
更新日期：2015-07-01 00:00:00
abstract：:To clarify whether expression of the programmed cell death 5 (PDCD5) gene in leukemic cells is abnormal, real-time quantitative reverse transcription polymerase chain reaction (RQ-RT-PCR) was used to examine its expression in marrow cells from leukemia patients. We found lower PDCD5 in both AML and CML marrow cells th...
journal_title：Leukemia research
pub_type： 杂志文章
doi：10.1016/j.leukres.2005.12.028
更新日期：2006-09-01 00:00:00
abstract：:Rhodamine 123 is transported by the transmembrane efflux pump P glycoprotein (Pgp). We used this fluorescent dye to study multidrug resistance (MDR) activity in normal and leukemic CD34+ cells. These immature cells had a high degree of MDR activity. Among leukemic cells, CD34+ leukemias had significantly higher MDR ac...
journal_title：Leukemia research
pub_type： 杂志文章
doi：10.1016/0145-2126(93)90159-i
更新日期：1993-12-01 00:00:00
abstract：:Forty-three patients were studied to determine whether light chain gene rearrangements may occur in hematopoietic cells not pertaining to the B-lineage. In only one patient, affected by T-cell lymphoblastic lymphoma, one kappa light chain allele was rearranged. Neither at the protein level nor at the RNA level the rea...
journal_title：Leukemia research
pub_type： 杂志文章
doi：10.1016/0145-2126(91)90145-j
更新日期：1991-01-01 00:00:00
abstract：:Many evidences have shown that dietary intake of cruciferous vegetables could protect against the risk of various types of malignancies. Benzyl isothiocyanate (BITC), one of the compounds from cruciferous vegetables, had shown induced cell cycle arrest and apoptosis in cancer cells. However, there is no available info...
journal_title：Leukemia research
pub_type： 杂志文章
doi：10.1016/j.leukres.2009.01.030
更新日期：2009-11-01 00:00:00
abstract：:Mutation of the tumor suppressor PTEN results in loss of its PI3-kinase counteracting function. PI3-kinase stimulates tumor formation by PKB/Akt-mediated cell proliferation and prevention of apoptosis. PI3-kinase may also activate Rho-GTPases and their regulatory GEFs to promote invasion. Here we have analyzed the fun...
journal_title：Leukemia research
pub_type： 杂志文章
doi：10.1016/j.leukres.2007.03.034
更新日期：2008-01-01 00:00:00
abstract：:In this study, the expression and functional characterization of currents through the CFTR (cystic fibrosis transmembrane regulator) and ORCC (outwardly rectifying chloride channels) were determined in wild-type K562 chronic human leukemia cells (K562-WT) and in its resistant counterpart, the vincristine resistant cel...
journal_title：Leukemia research
pub_type： 杂志文章
doi：10.1016/j.leukres.2005.02.007
更新日期：2005-09-01 00:00:00
abstract：:Oblimersen selectively targets Bcl-2 mRNA and has been shown to enhance the apoptotic activity of various antileukemic agents, including gemtuzumab ozogamicin (GO), in preclinical studies. We evaluated the efficacy and safety of oblimersen combined with GO in patients > or =60 years of age in first relapse with CD33+ ...
journal_title：Leukemia research
pub_type： 杂志文章,多中心研究
doi：10.1016/j.leukres.2005.10.025
更新日期：2006-07-01 00:00:00
abstract：:Predisposition to lymphomagenesis is a well-known phenomenon of ataxia-telangiectasia, a recessive disorder caused by germline inactivation of ATM. ATM encodes a protein implicated in the repair of radiation induced double-strand breaks. Biallelic ATM inactivation was described also in sporadic lymphoid malignancies, ...
journal_title：Leukemia research
pub_type： 杂志文章
doi：10.1016/j.leukres.2005.11.010
更新日期：2006-09-01 00:00:00
abstract：:In acute lymphoblastic leukemia (ALL) patients, automated fluorescence fragment analysis (ALF) has been reported to improve the monoclonality detection rate of immunoglobulin heavy chain genes (IgH) polymerase chain reaction (PCR) analysis. This study performed complementary determining region (CDR) I and III PCR on s...
journal_title：Leukemia research
pub_type： 杂志文章
doi：10.1016/s0145-2126(01)00025-x
更新日期：2001-09-01 00:00:00
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
doi：10.1016/0145-2126(89)90081-7
更新日期：1989-01-01 00:00:00
abstract：:The human cell line U-937 has many features suggestive of the monocyte. It may be stimulated in vitro to develop attributes of an activated macrophage with increased phagocytosis and enhanced Fc receptor expression. We describe the establishment of a subclone designated U-937 AG through the use of a mutagenic agent. T...
journal_title：Leukemia research
pub_type： 杂志文章
doi：10.1016/0145-2126(84)90084-5
更新日期：1984-01-01 00:00:00
abstract：:Apoptosis resistance is an important mechanisms of drug resistance mediated by bone marrow stromal cells (BMSCs). BMSCs influence tumor cells survival through several mechanisms including direct cell-cell contact and the effects of soluble factors. In this research we investigated the role of X-linked inhibitor of apo...
journal_title：Leukemia research
pub_type： 杂志文章
doi：10.1016/j.leukres.2006.09.006
更新日期：2007-08-01 00:00:00
abstract：:Post-transplant leukemic relapse remains the major problem following autologous bone marrow transplantation (ABMT). One possible approach to reducing the relapse rate is to intensify pre-transplant conditioning. Thiotepa (TTP) is an alkylating agent that has been used mainly in breast and ovarian cancer with 20-50% re...
journal_title：Leukemia research
pub_type： 临床试验,杂志文章
doi：10.1016/s0145-2126(98)00102-7
更新日期：1998-11-01 00:00:00
abstract：:Magnetic resonance provides a non-invasive tool for monitoring normal and leukemic bone marrow. Measurements of the T1 relaxation times are elevated in acute myelogenous leukemia. However, interpatient variability diminishes the usefulness of MR measurements for diagnosing leukemia. In following the time course of ind...
journal_title：Leukemia research
pub_type： 杂志文章
doi：10.1016/0145-2126(88)90034-3
更新日期：1988-01-01 00:00:00
abstract：:A patient with myelodysplastic syndromes (MDS) developed eosinophilia during treatment with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). To study the mechanism of this eosinophilia, we investigated the proliferation of eosinophil colony-forming units (CFU-Eo) in nine patients and four...
journal_title：Leukemia research
pub_type： 杂志文章
doi：10.1016/0145-2126(95)00083-6
更新日期：1995-12-01 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：:Clinicopathological features of 36 patients, male: 58.3%; median: 68 years, with "peripheral T-cell lymphoma, unspecified" diagnosed by the WHO criteria were reviewed. Majority (69.4%) had stage IV disease with frequent involvements into bone marrow, spleen, liver, and skin. According to the IPI, 72.2% were categorize...
journal_title：Leukemia research
pub_type： 杂志文章
doi：10.1016/j.leukres.2004.04.016
更新日期：2004-12-01 00:00:00
abstract：:We analyzed the biological activity of HA14-1, a small organic compound inhibitor of Bcl-2, against established leukaemia cell lines and blasts from acute myeloid leukaemia (AML) patients. HA14-1 had a potent killing activity against the leukaemia cell line that expressed endogenous or ectopic Bcl-2. This activity was...
journal_title：Leukemia research
pub_type： 杂志文章
doi：10.1016/j.leukres.2006.11.010
更新日期：2007-06-01 00:00:00
