Eph-A4 Plays a Important Role in Metastasis and Invasive Activity of Myeloid Leukemia Cells

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4819-4819
Author(s):  
Liu Xiaoli ◽  
Xuan Zhou ◽  
Yuan Zuo ◽  
Lulu Xu ◽  
Jinfang Zhang ◽  
...  
Keyword(s):  
Protein Expression ◽  
Cell Line ◽  
Myeloid Leukemia ◽  
Mrna Level ◽  
K562 Cells ◽  
Leukemia Cell Line ◽  
Leukemia Cells ◽  
Migration Assay ◽  
Wide Range ◽  
Myeloid Leukemias

Abstract Abstract 4819 The Eph receptors are found in a wide range of cancers and correlate with metastasis. However, their precise role in cancer has only started to be addressed. In this study, we investigated the role of Eph-A4 receptor in metastasis and invasive activity of myeloid leukemia cells. We fisr tested the expression of Eph-A4 in eight primary myeloid leukemias imclulding four with extramedullary metastasis and four without it, and leukemia cell line K562 by Real-time PCR and western blotting, then found that Eph- A4 was wildly expressed in myeloid Leukemia cells, especially in myeloid leukemia cells with high invasive activity. To further clarified the question, the stable over-expressing Eph-A4 cell line (K562-EphA4) based the wild K562 cell and pGC lentivirus vector were established to declare the metastasis and invasive activity in myeloid leukemia cells in vitro by trans-well migration assay. The results indicated that the mRNA level and protein expression of Eph-A4 were significantly increased in myeloid leukemias with extramedullary metastasis and K562 cells compared to those without it (P<0.05).After we successfully established the stable over-expressing Eph-A4 cell line, we verified its mRNA level and protein expression were both significantly increased ((P<0.05).Furthermore, RhoA and Rac1/cdc42, which are important adhesion molecules and related to metastasis and invasive activity were both highly expressed in K562-EphA4 cells compared to wild K562 cells (P<0.05). Moreover, the trans-well migration assay showed that cells that migrated to lower chambers and matrigel hydrogel were both increased in K562-EphA4 cells compared to wild K562 cells (5.22±2.11*104/ml vs 13.56±2.70*104 /ml P<0.000;18.07±3.15/cm2 vs 28.53±2.50/cm2P<0.000 respectively). Our findings suggest that Eph- A4 is likely to play an important role in the regulation the of myeloid Leukemia through the control of RhoA and Rac1/cdc42 associated signaling, migration and invasive activity, and therefore may represent a novel target for cancer treatment. Disclosures: No relevant conflicts of interest to declare.

Decreased Proliferation of Myeloid Leukemia Cells through Down-Regulating LYL1 Expression with Small Interference RNA.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4158-4158 ◽  
Author(s):  
Yuesheng Meng ◽  
Wei Liu ◽  
Xiaoxia Ma ◽  
Xiuqin Meng ◽  
Gongwen Ai ◽  
...  
Keyword(s):  
Growth Rates ◽  
Myeloid Leukemia ◽  
K562 Cells ◽  
Plating Efficiency ◽  
Leukemia Cell Line ◽  
Leukemia Cells ◽  
Human Leukemia ◽  
Small Interference Rna ◽  
Expression Levels ◽  
Interference Rna

Abstract Ectopic expression of the basic helix-loop-helix transcription factor LYL1 has been implicated in T-cell acute lymphoblastic leukemia (T-ALL). It has also been found to be over-expressed in cells of acute myeloid leukemia (AML). Myeloid leukemia cells over-expressing LYL1 cDNA had accelerated growth rates, increased plating efficiency and a blockade of differentiation. To further investigate its role in the pathogenesis of leukemia, we used small interference RNA (siRNA) to silence the expression of LYL1 in human leukemia cell line K562, which expresses a moderate level of endogenous LYL1 protein. Three LYL1-specific RNA oligos, the Stealth Select RNAi HSS142834, HSS142835, and HSS142836, purchased from Invitrogen, were introduced into K562 cells by using Invitrogen transfection reagent Lipofectamine RNAiMAX. Two successive transfections at day 1 and day 2 were made according to manufacturer’s manual. Expression levels of LYL1 in LYL1 siRNA transfected cells and control cells (transfected with the Stealth RNAi Negative Controls) were determined with fluorescence real-time quantitative polymerase chain reaction assay. Our result showed that the application of any single RNAi oligo achieved observable inhibition of LYL1 expression levels (30–40%) while a combination of the three RNAi oligos remarkable inhibition (70.4%). The growth rates of K562 cells were not affected by any single RNAi oligo. However, a combination of three RNAi oligos did induce noticeable growth inhibition of cells. Plating efficiency assay showed that the clonogenic recovery rate of K562 cells treated with a combination of thee RNAi oligos was inhibited by 32.5% (P<0.05). The reduced growth rate and clonogenicity of cells was supposed to be secondary to the repressed expression of LYL1 because all other factors were controlled in our experiments. Further experiments are underway to define the changes of other genes in the LYL1-suppressed cells. We also tested the effect of specific siRNA on the expression of LYL1 and clonogenecity of leukemia cells in patient samples. Mononuclear cells separated from nine newly-diagnosed AML patients whose cells expressed comparatively higher levels of LYL1 were transfected with a combination of three LYL1 specific siRNA oligos for twice. We found that the siRNA oligos suppressed the expression of LYL1 in leukemia cells in most of the patients (7/9, decreased by 2 times or more) when compared with controls. Remarkably, the clonogenicity of AML cells in 3 patients was also inhibited by siRNA (P<0.05). In conclusion, the specific siRNA was effective to downregulate the expression of LYL1 in myeloid leukemia cells. It was also effective to affect cell proliferation in some cases. The data demonstrates that LYL1 plays a role for the malignant genotypes of leukemia cells and suggests that the RNA interference therapy targeting specific oncogenes might be clinically useful in the management of hematological malignancies.

scholarly journals Orlistatand and Rosuvastatin Suppressed Proliferation of K562 Human Myelogenous Leukemia Cell Line through AMPK/Akt/c-Myc Signaling

2020 ◽  
Author(s):  
Behnam Mojjarad ◽  
Yaghub Pazhang
Keyword(s):  
Cell Cycle ◽  
Chronic Myeloid Leukemia ◽  
Cell Line ◽  
Myeloid Leukemia ◽  
Leukemia Cell ◽  
K562 Cells ◽  
Myelogenous Leukemia ◽  
Leukemia Cell Line ◽  
Mrna Levels ◽  
Hsp 70

Abstract Background: Chronic myeloid leukemia is a myeloproliferative cancer with worldwide incidence, has become as a clinical concern due to chemoresistance in the patients received chemotherapy. Here, we investigated the effect of Orlistat and Rosuvastatin on K562 human myelogenous leukemia cell line in vitro and attempted to illuminate their possible underlying mechanisms. Methods: Cells were exposed to Orlistat and Rosuvastatin, the inhibitors of lipogenesis, then survival and apoptosis rate of K562 cells were examined by MTT assay and flow cytometric analysis respectively. The real time-PCR analysis was used to quantify mRNA levels of Bax, Bcl-2, and Hsp-70 genes. Cell cycle analysis was performed using flow cytometry, whereas the subcellular distribution of c-Myc was measured via immunofluorescence imaging technique. Additionally, the protein level of AMPK, p-AMPK Akt-1, and p-Akt-1 were studied by western blotting. Results: The results showed Orlistat and Rosuvastatin had synergistic anticancer effects on cells and in comparison with the control group, viability and apoptosis rate decreased and increased in treated cells respectively in a dose/time-dependent manner (P<0.05). The mRNA levels of Bax increased while expression of Hsp-70 decreased (P< 0.05). K562 cells treated with Orlistat and Rosuvastatin showed a cell cycle arrest in sub-G1 phase and a decreased level of c-Myc positive cells. Upon outlining the mechanism, it was revealed that AMPK/p-AMPK and p-Akt-1/Akt-1 ratio decreased in treated cells (P< 0.05). Conclusions: Data suggest Orlistat and Rosuvastatin could synergically suppress proliferation of K562 cells through AMPK/Akt/c-Myc axis, proposing a theoretical basis for upcoming application in the treatment of chronic myeloid leukemia

The Apoptosis of Acute Myeloid Leukemia Cell Line (SHI-1 cells) Induced by Bortezomib In Vitro

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4382-4382
Author(s):  
Mingzhen Yang ◽  
Xiaoyu Zhang ◽  
Zhenqi Huang ◽  
Qingsheng Li ◽  
Lin Wang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Protein Expression ◽  
Proteasome Inhibitor ◽  
Myeloid Leukemia ◽  
Critical Role ◽  
Leukemia Cell ◽  
Myelogenous Leukemia ◽  
Leukemia Cell Line ◽  
Leukemia Cells ◽  
Acute Myeloid

Abstract Abstract 4382 Background: The proteasome plays a critical role in the regulation of many cellular processes, including the cell cycle and tumor growth. The proteasome inhibitor Bortezomib has been used in multiple myeloma and other lymphoid malignancies because of its antitumor activity. Here we investigated the induction of apoptosis by proteasome inhibitor Bortezomib in human acute myeloid leukemia (AML) cell lines SHI-1 cells and try to explore the mechanism of anti-leukemia. Method: We incubated SHI-1 leukemic cells with different concentration of bortezomib. cell proliferation was detected with MTT, apoptosis was measured by FCM, the protein expression of PI3K and p-Akt were determined by Western blot. Result: 0.5ug/ml bortezomib suppressed SHI-1 cells proliferation and induced SHI-1 cells apoptosis after incubated 24hr, 100ug/ml bortezomib suppressed 61.7% SHI-1 cells proliferation. Apoptosis increased obviously with the increasing bortezomib concentration and the culture time, about 39.77% SHI-1 cells were apoptosis when bortezomib concentration was 100ug/ml, the leukemia cell apoptosis was significant at 150ng/ml bortezomib, the protein expression of PI3K, and p-Akt gradually declined with bortezomib concentration increasing, The protein expression of PI3K and p-Akt in SHI-1 cells decreased 50.6% and 71.6% respectively at 100ug/ml bortezomib for 48hr.when 150ng/ml bortezomib incubated with leukemia cells for 24 hours, The protein expression of PI3K and p-Akt were lowest. Conclusion: Bortezomib could inhibit SHI-1 cells proliferation and induce leukemia cells apoptosis, and could down-regulate the expression of PI3K and p-Akt significantly, this might be the one of mechanisms that bortezomib induce SHI-1 cells apoptosis, we presume that bortezomib inhibit proliferation of acute myelogenous leukemia cells through effect of PI3K/Akt signaling pathways. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Effects of CCL2/CCR2 Blockade in Acute Myeloid Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1348-1348 ◽  
Author(s):  
Rodrigo Omar Jacamo ◽  
Hong Mu ◽  
Qi Zhang ◽  
Dhruv Chachad ◽  
Wang Zhiqiang ◽  
...  
Keyword(s):  
Cell Line ◽  
Stromal Cells ◽  
Myeloid Leukemia ◽  
Hematopoietic Cells ◽  
Fold Increase ◽  
In Vivo Studies ◽  
Leukemia Cell Line ◽  
Leukemia Cells ◽  
Tumor Associated Macrophages

Abstract Background: A role for the Chemokine (C-C motif) ligand 2 (CCL2) in attracting tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSC) and infiltrating monocytes has been described for many solid tumors in which they play an essential role in modifying the adaptive immune response, ultimately favoring tumor progression. Unfortunately, little is known about the importance of this mechanism for the progression of AML. We recently identified CCL2 as the most prominent chemokine produced by bone marrow (BM) mesenchymal stromal cells (BM-MSC) in response to the interaction with myeloid leukemia cells (PMID: 24599548). In addition, elevated CCL2 plasma levels have been reported in patients of AML (PMID: 17822317), ALL (PMID: 21298741) and CLL (PMID: 22397722) when compared to normal controls. In this study we assessed the effects of blocking the CCR2-CCL2 axis on the migration and signaling of hematopoietic cells as well as on the infiltration of immune-suppressive cells in leukemia-bearing mice. Results: We first studied the efficacy and potency of agents at inhibiting CCL2-mediated migration, using the human monocytic leukemia cell line THP-1. Migration towards human recombinant CCL2 (5 ng/ml) was significantly inhibited by as little as 1 nM of NOX-E36, a human-specific CCL2 Spiegelmer (NOXXON Pharma, Berlin). Spiegelmers are RNA-like molecules built from L-ribose units that are able to bind molecules such as peptides and proteins with an affinity in the pico-to nanomolar range. Similar results were obtained with a CCR2 antagonist (100 ng/ml; Santa Cruz). In anticipation of in vivo studies in mice, we next confirmed the ability of a mouse-specific CCL2 Spiegelmer (mNOX-E36) to inhibit migration and signaling pathway activation in murine hematopoietic cells. For this purpose, we cloned and overexpressed via lentiviral transduction the murine CCL2 receptor (CCR2) in Ba/F3 cells (a murine pro-B cell line). Stimulation of Ba/F3-CCR2 cells with 5 ng/ml of mouse recombinant CCL2 induced a ~2000 fold increase in migration of Ba/F3-CCR2 cells and was successfully blocked with mNOX-E36 in a concentration-dependent manner. Western blot analysis of protein lysates from mCCL2-stimulated cells (30 minutes treatment) indicated activation of AKT, ERK and p38-MAPK. The CCL2-induced phosphorylation of these molecules was completely abrogated by pre-treatment with mNOX-E36. Subsequently, we determined whether the expression of CCL2 by stromal cells in leukemia-resident organs triggers the infiltration of TAMs and possibly other immune-suppressive cells into those organs. We conducted preliminary in vivo studies in non-irradiated immunocompetent C57BL/6 mice (n=5 per group) injected with syngeneic AML1/ETO9a-expressing primary murine leukemia cells (PMID: 19339691). After confirmation of leukemia engraftment by IVIS imaging, mice were treated with mNOX-E36 (14.4 mg/kg, s.c., three times per week) or vehicle control for 3 weeks. At this point, all animals were sacrificed and their tissues (spleens and BM from femurs) were collected for analysis. Although we did not observe differences in leukemia burden by imaging between vehicle and mNOX-E36 treated groups, flow cytometry analysis revealed an increase in the frequency of CD11b+ Ly6Clow MHC IIlow macrophages (2 to 7 fold increase) in spleens of mice engrafted with leukemia (vehicle-treated group) when compared to spleens collected from healthy mice. These MHC IIlow macrophages were previously identified as immunosuppressive M2-like macrophages as opposed to MHC IIhi macrophages which show a pro-inflammatory M1-like phenotype (PMID: 20570887). Importantly, CCL2 inhibitor mNOX-E36 abrogated this macrophage infiltration within the leukemia microenvironment. Conclusions: Our results indicate that blockade of the CCR2-CCL2 axis not only affects migration and signaling of treated cells in vitro, but also interferes with the infiltration of M2-like macrophages into spleens of leukemia-bearing mice. Current in vivo experiments using a combination of standard chemotherapy with mNOX-E36 in AML immunocompetent models are undergoing. We expect that in vivo modulation of CCL2 will improve response to chemotherapy of AML by reducing the marrow infiltration of infiltrating monocytes and tumor-associated macrophages, which would facilitate translation of this novel concept into clinical trials in AML. Disclosures Zuber: Boehringer Ingelheim: Research Funding; Mirimus Inc.: Consultancy, Other: Stock holder. Eulberg:NOXXON Pharma AG: Employment. Kruschinski:NOXXON Pharma AG: Employment.

Characterization of Cancer Stem-Like Cells in a Novel STI571-Resistant Chronic Myeloid Leukemia Cell Line.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4852-4852
Author(s):  
Yongping Song ◽  
Baijun Fang ◽  
Yanli Zhang ◽  
Xudong Wei ◽  
Lulu Lu ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Cell Line ◽  
Myeloid Leukemia ◽  
Side Population ◽  
Leukemia Cell ◽  
K562 Cells ◽  
Leukemia Cell Line ◽  
Small Subpopulation

Abstract To characterize a novel chronic myeloid leukemia (CML) cell line and to further elucidate the mechanisms of resistance to STI571, a novel K562 cell line (K562/VP16) was achieved after exposure of the K562 cells in gradually increasing concentrations of VP16 over a period of several months. A small subpopulation (K562/VP16 SP) that was capable of excluding Hoechst 33342 in the K562/VP16 cell line was isolated by flowcytometry sorting. The rest of the K562/VP16 cells were classified as non-SP K562/VP16. The mechanisms involved in K562/VP16 SP cells that became resistant to STI571 were studied. We found that the levels of Bcr-Abl and Abl proteins were similar in the K562 cells and in non-SP K562/VP16 and K562/VP16 SP cells. The MDR-1 gene expression of the 170 kDa P-gp was detected in K562/VP16 non-SP and K562/VP16 SP cells but not in K562 cells. The expression levels of P-gp in the two K562/VP16 cell lines were similar. Furthermore, there were no mutations of Abl in the K562/VP16 SP cells. Compared with non-SP K562/VP16, the K562/VP16 SP cells were more resistant to STI571, and many multidrug resistance inhibitors could hardly reverse this resistance. In addition, in vivo study showed that the K562/VP16 SP cells induced tumorigenesis in mice, while the K562/VP16 non-SP cells failed to do so. These results suggest that a small side population K562/VP16 SP cells in K562/VP16 cell line, had high resistance to STI571 treatment and more tumorigenic than the K562 cells and it may represent the cancer stem cells of the K562/VP16 cell line.

Cytotoxic T-Lymphocyte Harnessing CML66 Can Kill Human Myeloid Leukemia Cells, In Vitro.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2746-2746
Author(s):  
Koichiro Suemori ◽  
Hiroshi Fujiwara ◽  
Toshiki Ochi ◽  
Masaki Yasukawa
Keyword(s):  
Cell Line ◽  
Myeloid Leukemia ◽  
Cytotoxic T Lymphocyte ◽  
Leukemia Cell ◽  
Myelogenous Leukemia ◽  
Expression Level ◽  
Leukemia Cell Line ◽  
Leukemia Cells ◽  
Myeloid Leukemia Cell

Abstract [Purpose & background] CML66 is a newly identified cancer-testis antigen by SEREX method in post-transplant CML patient who had a second remission by DLI for relapse. Thus CML66 is initially considered to be implicated in graft-versus-leukemia (GvL) effect against CML, while its’ physiological function remains unknown. The identification by SEREX means its’ immunogenicity to produce antibody, however the T-cell response specific for CML66, particularly its’ ability to generate cytotoxic T-lymphocyte (CTL) against leukemia still remains to be verified. Thus we explored a CTL-epitope of CML66 to induce epitope-specific CTL which can kill human leukemia cells, because of the exploration of its’ clinical applicability as an anticancer vaccine for the immunotherapy. [Methods] At first, we synthesized a variety of CML66-derived 9 aminoacid peptides (9 mer) that had computedly-predicted high binding affinity to HLA-A*2402 molecule. CD8+ T lymphocytes from an HLA-A*2402+healthy donor were co-cultured with autologous monocyte-derived mature dendritic cells (mDCs). CD8+T lymphocytes were repeatedly stimulated with peptide-loaded mDCs. Thereafter, the target epitope-specificity of growing cells was examined by a standard 51Cr-release assay. Additionally, the blocking tests by using anti-HLA class I and anti-class II monoclonal antibody (mo.ab.) were conducted to confirm its’ HLA-A*2402-restricted fashion. Next, CML66 mRNA expression level of target cells including myeloid leukemia cell line cells and primary leukemia cells was examined by real-time semi-quantitative PCR (RQ-PCR). The relative expression level of CML66 mRNA was determined by comparative Ct method. [Result] We identified two CML66-derived 9 mer epitopes with high binding affinity to HLA-A*2402 measured by using HLA-A*2402 gene transfected T2 (T2-A24) cell. One of 2 epitopes, the epitope of CML66; aa70–78: WIQDSVYYI generated the epitope-specific CTL, in vitro, and those CTL exerted anti-leukemia activity against human myeloid leukemia cell line cells in an HLA-A*2402-restricted fashion, but not any cytotoxicity against normal cells. Furthermore, the HLA-A*2402 restriction was confirmed by blocking test by HLA-class I and II mo.ab. Next CML66 mRNA expression level was revealed high in myeloid leukemia cell line cells but low in normal cells, which were compared to that of K562 cell line cell. In primay leukemia cells, acute myelogenous leukemia(AML) cells and acute lymphoblastic leukemia(ALL) cells showed the high expression level of CML66 mRNA. Regarding to the FAB classification of AML, the expression level of CML66 mRNA tended to be higher in subsets ranging from M1 to M4, particularly M2 cells. Even by small number, it was of interest that the expression level of CML66 mRNA in primary chronic myelogenous leukemia (CML) cells was high in cells from blastic phase, but low in cells from chronic phase. This finding may suggest the correlation between CML66 and growth activity of tumor cells. [Conclusion] We identified the novel HLA-A*2402 restricted CTL-epitope derived from CML66; aa70–78: WIQDSVYYI, which may be a promising and secure target for immunotherapy against acute leukemias and aggressive CML.

scholarly journals Changes in contractile proteins during differentiation of myeloid leukemia cells. I. Polymerization of actin.

1980 ◽  
Vol 85 (2) ◽  
pp. 273-282 ◽  
Author(s):  
K Nagata ◽  
J Sagara ◽  
Y Ichikawa
Keyword(s):  
Cell Line ◽  
Conditioned Medium ◽  
Mitotic Activity ◽  
Myeloid Leukemia ◽  
Leukemia Cell ◽  
Leukemia Cell Line ◽  
Leukemia Cells ◽  
Before And After ◽  
Myeloid Leukemia Cell ◽  
Qualitative Changes

Quantitative and qualitative changes in cellular actin were followed during differentiation of a myeloid leukemia cell line, namely Ml, which was inducible with conditioned medium (CM). During 3 d of incubation with CM, when the Ml cells differentiated to macrophages and lost their mitotic activity, the actin content, F-actin ratio in total actin, and the actin synthesis showed an increase. A greater difference before and after differentiation was found in the ability of G-actin to polymerize. Actin harvested from CM-treated cells showed a greater ability to polymerize, depending on the increased concentration of MgCl2 and/or KCl and proteins, as compared with the actin from untreated Ml cells. Actin harvested from the Mml cell line, a macrophage line, had a particularly high polymerizability with or without CM treatment. In contrast, the actin from the D- subline, which is insensitive to CM, showed almost no polymerization.

scholarly journals Orlistatand and Rosuvastatin Suppressed Proliferation of K562 Human Myelogenous Leukemia Cell Line through AMPK/Akt/c-Myc Signaling

2020 ◽  
Author(s):  
Behnam Mojjarad ◽  
Yaghub Pazhang
Keyword(s):  
Cell Cycle ◽  
Chronic Myeloid Leukemia ◽  
Cell Line ◽  
Myeloid Leukemia ◽  
Leukemia Cell ◽  
K562 Cells ◽  
Myelogenous Leukemia ◽  
Leukemia Cell Line ◽  
Mrna Levels ◽  
Hsp 70

Abstract Background: Chronic myeloid leukemia is a myeloproliferative cancer with worldwide incidence, has become as a clinical concern due to chemoresistance in the patients received chemotherapy. Here, we investigated the effect of Orlistat and Rosuvastatin on K562 human myelogenous leukemia cell line in vitro and attempted to illuminate their possible underlying mechanisms. Methods: Cells were exposed to Orlistat and Rosuvastatin, the inhibitors of lipogenesis, then survival and apoptosis rate of K562 cells were examined by MTT assay and flow cytometric analysis respectively. The real time-PCR analysis was used to quantify mRNA levels of Bax, Bcl-2, and Hsp-70 genes. Cell cycle analysis was performed using flow cytometry, whereas the subcellular distribution of c-Myc was measured via immunofluorescence imaging technique. Additionally, the protein level of AMPK, p-AMPK Akt-1, and p-Akt-1 were studied by western blotting.Results: The results showed Orlistat and Rosuvastatin had synergistic anticancer effects on cells and in comparison with the control group, viability and apoptosis rate decreased and increased in treated cells respectively in a dose/time-dependent manner (P<0.05). The mRNA levels of Bax increased while expression of Hsp-70 decreased (P< 0.05). K562 cells treated with Orlistat and Rosuvastatin showed a cell cycle arrest in sub-G1 phase and a decreased level of c-Myc positive cells. Upon outlining the mechanism, it was revealed that AMPK/p-AMPK and p-Akt-1/Akt-1 ratio decreased in treated cells (P< 0.05).Conclusions: Data suggest Orlistat and Rosuvastatin could synergically suppress proliferation of K562 cells through AMPK/Akt/c-Myc axis, proposing a theoretical basis for upcoming application in the treatment of chronic myeloid leukemia.

scholarly journals Retinoic acid-induced granulocytic differentiation of HL-60 myeloid leukemia cells is mediated directly through the retinoic acid receptor (RAR-alpha).

1990 ◽  
Vol 10 (5) ◽  
pp. 2154-2163 ◽  
Author(s):  
S J Collins ◽  
K A Robertson ◽  
L Mueller
Keyword(s):  
Retinoic Acid ◽  
Myeloid Leukemia ◽  
Retinoic Acid Receptor ◽  
Leukemia Cell ◽  
Single Copy ◽  
Leukemia Cell Line ◽  
Leukemia Cells ◽  
Granulocytic Differentiation ◽  
Myeloid Leukemias ◽  
Promyelocytic Leukemia Cell Line

Retinoic acid (RA) induces terminal granulocytic differentiation of the HL-60 promyelocytic leukemia cell line as well as certain other human myeloid leukemias. Specific RA receptors that are members of the steroid-thyroid hormone superfamily of nuclear transcription factors have recently been identified. We developed an HL-60 subclone that was relatively resistant to RA-induced differentiation. Specific nuclear RA receptors in this RA-resistant subclone had a decreased affinity for RA and exhibited a lower molecular weight compared with nuclear RA receptors from the RA-sensitive parental HL-60 cells. Retroviral vector-mediated transduction of a single copy of the RA receptor (RAR-alpha) into this RA-resistant HL-60 subclone restored the sensitivity of these cells to RA. These observations indicate that RAR-alpha plays a critical and central role in mediating RA-induced terminal differentiation of HL-60 leukemia cells.

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