Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was aimed to explore the expression of MIP-1alpha, MCP-1 and their receptors CCR-1, CCR-2 in bcr/abl fusion gene positive CML cells, and to study the effects of P210(bcr/abl) fusion protein tyrosine kinase on expression of MIP-1alpha, MCP-1 and their receptors CCR-1, CCR-2 mRNAs in chronic myeloid leukemia cells. The expression levels of MIP-1alpha, MCP-1 and their receptors CCR-1, CCR-2 mRNA were detected by semi-quantitative RT-PCR in bcr/abl negative cells, bcr/abl positive cells, and P210(bcr/abl)-Rb-C-Box positive cells. The results showed that MIP-1alpha and CCR-1 mRNAs were expressed in bcr/abl negative cells, but not in positive cells. Both MCP-1 and CCR-2 mRNA cannot be detected in both bcr/abl positive and negative cells. After inhibiting P210(bcr/abl) tyrosine kinase activity by Rb-C-Box, expressions of MIP-1alpha and CCR-1 mRNAs were restored to normal (similar to P210(bcr/abl) negative cells). It is concluded that P210(bcr/abl) fusion protein inhibits the expression of MIP-1alpha and CCR-1 in chronic myeloid leukemia cells, but does not inhibit MCP-1 and CCR-2 mRNA expressions in these leukemia cells.
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PMID:[Expressions of MIP-1alpha, MCP-1 and their receptors CCR-1, CCR-2 in chronic myeloid leukemia cells]. 1680 Sep 14

Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disease of transformed hematopoietic progenitor cells. It is now clear that the chimeric bcr/abl P210(bcr/abl) fusion protein, which is generated by the reciprocal translocation t (9; 22), inhibits apoptosis and increase proliferation. P210(bcr/abl) plays a central role in the pathophysiology of CML. The purpose of this study was to construct a cell line model that bcr/abl expression can be regulated by Tet-off inducing-expression-system. The full-length b3a2 bcr/abl cDNA was subcloned into the pTRE2hyg expression vector to construct the pT2-P210 plasmid. 293 cells were firstly transfected with Tet-off plasmid and the clone that the Tet-off system can work effectively after transfected with pTRE2hyg-LUC was selected by luciferase activity assay. The pT2-P210 plasmid was then transfected into the selected clone and cells were then selected for hygromycin B and G418 resistance. The results showed that individual subclones expressing bcr/abl after withdrawing doxycycline were 293pT2-P210 cell line. In conclusion, selected 293pT2-P210 cells are cells that bcr/abl expression can be regulated by Tet-off inducing-expression-system. They are suitable thoroughly to study the function of bcr/abl fusion gene and its signal regulation mechanism.
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PMID:[Construction of 293pT2-P210 cell line enables expression of bcr/abl to be regulated by Tet-off inducing-expression-system]. 1749 20

Reduced lymphopoiesis during aging contributes to declines in immunity, but little consideration has been given to its effect on the development of hematologic disease. This report demonstrates that age-related defects in lymphopoiesis underlie the myeloid dominance of adult leukemia. Using a murine model of chronic myeloid leukemia, an adult-onset malignancy that arises from transformation of hematopoietic stem cells by the BCR-ABL(P210) oncogene, we demonstrate that young bone marrow (BM) cells that were transformed with BCR-ABL(P210) initiated both a myeloproliferative disorder (MPD) and B-lymphoid leukemia, whereas BCR-ABL(P210)-transformed old BM cells recapitulated the human disease by inducing an MPD with rare lymphoid involvement. In addition, the lesser severity of MPDs initiated from old BCR-ABL(P210)-transduced BM cells revealed unappreciated defects in aged myeloid progenitors. These data demonstrate that aging affects patterns of leukemogenesis and indicate that the effects of senescence on hematopoiesis are more extensive than previously appreciated.
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PMID:Age-related defects in B lymphopoiesis underlie the myeloid dominance of adult leukemia. 1755 60

Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disease of transformed hematopoietic progenitor cells. In order to investigate the role of sphingosine kinase-1 (SphK-1)/sphingosine 1-phosphate (S1P) signal pathway in the expression of CML cells, and to explore whether P210(bcr/abl) involved is activating SphK-1/S1P signal pathwey, the expressions of SphK-1 and S1P receptor mRNA in bcr/abl positive K562 cells and bcr/abl positive primary CML cells were detected by RT-PCR, the imatinib mesylate, the specific inhibitor of P210(bcr/abl) was employed to inhibit the P210(bcr/abl) tyrosine kinases of K562 cells and CML primary cells, and then the intracellular SphK-1 activity was assayed. The results indicated that after being cultured with 2.5 micromol/L imatinib mesylate for 0.5, 2, 6, 24 and 48 hours, the intensions of inhibiting SphK-1 activity were 0.007%, 38.9%, 34.6%, 28.1% and 76.1% resepectively. SphK-1 activity in CML cells also was reduced by 2.5 micromol/L imatinib mesylate (16.8% - 41.9% decrease). It is concluded that the CML cells express SphK-1 and different S1P receptor, and P210(bcr/abl) fusion protein in CML cells can activate SphK-1.
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PMID:[SphK-1/S1P signal pathway in CML cells]. 1871 48

Chronic myeloid leukemia (CML) is typified by robust marrow and extramedullary myeloid cell production. In the absence of therapy or sometimes despite it, CML has a propensity to progress from a relatively well tolerated chronic phase to an almost uniformly fatal blast crisis phase. The discovery of the Philadelphia chromosome followed by identification of its BCR-ABL fusion gene product and the resultant constitutively active P210 BCR-ABL tyrosine kinase, prompted the unraveling of the molecular pathogenesis of CML. Ground-breaking research demonstrating that BCR-ABL was necessary and sufficient to initiate chronic phase CML provided the rationale for targeted therapy. However, regardless of greatly reduced mortality rates with BCR-ABL targeted therapy, most patients harbor quiescent CML stem cells that may be a reservoir for disease progression to blast crisis. While the hematopoietic stem cell (HSC) origin of CML was first suggested over 30 years ago, only recently have the HSC and progenitor cell-specific effects of the molecular mutations that drive CML been investigated. This has provided the impetus for investigating the genetic and epigenetic events governing HSC and progenitor cell resistance to therapy and their role in disease progression. Accumulating evidence suggests that the acquired BCR-ABL mutation initiates chronic phase CML and results in aberrant stem cell differentiation and survival. This eventually leads to the production of an expanded progenitor population that aberrantly acquires self-renewal capacity resulting in leukemia stem cell (LSC) generation and blast crisis transformation. Therapeutic recalcitrance of blast crisis CML provides the rationale for targeting the molecular pathways that drive aberrant progenitor differentiation, survival and self-renewal earlier in disease before LSC predominate.
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PMID:Chronic myeloid leukemia stem cells. 1907 22

The BCR/ABL fusion oncogene found in Philadelphia-positive leukemia exists in three principle forms: p190, p210 and p230. P210 BCR/ABL is commonly found in patients with chronic myelogenous leukemia (CML) and is further categorized into b3a2 or b2a2 subtypes on the basis of the BCR breakpoint. Although these 2 subtypes may be clinically heterogeneous, only the b3a2 BCR/ABL gene has been extensively studied at the molecular and cellular levels. In the present study, we compared the in vivo leukemogenic activity of the b3a2 and b2a2 BCR/ABL genes by using lentiviral transduction/transplantation mouse models. Lineage-depleted bone marrow cells of BALB/c mice were transduced with a lentiviral vector including either b2a2 or b3a2 BCR/ABL cDNA and then transplanted into lethally irradiated mice. In this model, p210 BCR/ABL subtype developed only B220(+), CD3e(-), Gr1(-), and Mac1(-) B-cell acute lymphoblastic leukemia but not myeloid leukemia. There were no differences in the incidence of leukemogenesis, the white blood cell count, the percentage of blast cells, or the survival rates between the b2a2 and b3a2 groups. We have demonstrated that b2a2-type BCR/ABL has leukemogenic activity similar to that of b3a2-type BCR/ABL.
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PMID:Leukemogenesis of b2a2-type p210 BCR/ABL in a bone marrow transplantation mouse model using a lentiviral vector. 1960 20

This study was purposed to set up real-time quantitative RT-PCR technique and to measure leukemia fusion gene transcripts in patients with chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL) and acute promyelocytic leukemia (APL). All plasmids containing the target gene sequences were constructed to establish the standard curves. A TaqMan based real-time quantitative RT-PCR was performed to measure aberrant fusion gene transcripts in 130 samples of peripheral blood (PB) or bone marrow (BM) from 49 patients with leukemia. The results showd that the BCR-ABL(P210) transcripts were detected in 28 (82.4%) out of 34 CML patients (the ratios of BCR-ABL(P210)/ABL varied from 0.01 to 3.19) and also in 2 (33.3%) out of 6 ALL patients. The BCR-ABL(P190) transcripts were detected in 2 (33.3%) out of 6 ALL patients. The BCR-ABL(P210) and BCR-ABL(P190) transcripts were both detected in 1 (2.9%) CML patients. The PML/RARalpha transcripts were detected in 7 (77.8%) out of 9 APL patients (the ratio of PML-RARa/ABL varied from 0.0014 to 3.199). The relative frequency of both bcr1 and bcr3 was 42.9%, while that of bcr2 was 14.3%. The transcript level of aberrant fusion gene varied from the clinical situation of patient. It is concluded that real-time quantitative PCR is a reliable, innovative and promising technology with high sensitivity and specialty. It has potential clinical value for defining diagnosis, typing tumor, selecting treatment, measuring the tumor load, monitoring fusion gene expression level and evaluating therapeutic strategies, which is worthy to be popularized.
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PMID:[Detection and quantification of aberrant leukemia fusion gene by real-time RT-PCR]. 1969 40

The aim of this study was to investigate the ability of calcium ionophore (CI ) to induce the differentiation of CML cells into dendritic cells (DC), to analyze the P210 expression in DCs and to evaluate the stimulatory effect of CML-DC on production of cytotoxic activity against CML cells via activating the autologous T cells. The mononuclear cells were isolated from bone marrow of CML patients whose WBC counts were more than 30x10(9)/L when samples were collected, then the lymphocytes and monocytes were discarded by pouring out supernatant twice at different culture time point. Slightly adherent cells were cultured in RPMI 1640 containing 10% FCS, with or without CI (375 ng/ml) and GM-CSF (200 ng/ml) at 37 degrees C, 5% CO2, fully humidified atmosphere for 96 hours. The cell morphology was observed under the inverted microscope and electron microscope; the expression of CD antigens was analyzed with flow cytometry; the P210 expression was measured with Western blot. LDH assay was used to evaluate the effect of cultured CML cells (CML-DC) generating cytotoxic T lymphocyte (CTL) activity against CML cells. The results indicated that after treatment with calcium ionophore and GM-CSF for 96 hours, CML cells showed DC morphological characteristics under inverted microscope and electron microscope. The expression of CD83, CD86, CD40, CD80 and HLA-DR increased remarkably. P210 was expressed in the CML-DC, but the expression level was lower than that in CML cells without CI and GM-CSF treatment. LDH assay showed that the CTL activity against CML was found greater in autologous T cells activated by CML-DC than that by CML cells. It is concluded that the CML cells can be induced to quickly differentiate into DC when cultured with CI and GM-CSF. CML-DC expresses P210, but the expression level is lower than that in CML cells. CML-DC can stimulate autologous T cells to produce CTL against CML.
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PMID:[Calcium ionophore induces the differentiation of chronic myeloid leukemia cells into dendritic cells]. 1984 Apr 48

The study was aimed to investigate the effects of emodin on proliferation inhibition and apoptosis induction in human chronic myeloid leukemia cell line K562 cells, and to explore the role of P210 protein and activation of caspase 3 in these processes. K562 cells were exposed to emodin at different doses. The proliferation inhibition was detected by MTT assay and colony formation test. The ability of emodin to induce apoptosis and DNA fragmentation were examined by flow cytometry. The expressions of P210, procaspase-3 and PARP protein were determined by Western blot. The results indicated that the emodin remarkably inhibited the K562 cell proliferation, with IC(50) value of 38.25 micromol/L after treatment for 48 hours. Meanwhile induced apoptosis, Annexin V-FITC positive cells, sub-G(1) apoptotic peak and DNA fragmentation in K562 cells confirmed that emodin induced apoptosis in K562 cells in dose-dependent manner. Western blot results showed that emodin inhibited phosphorylation of P210 protein in K562 cells and down-regulated the expression levels of P210. The procaspase-3 level in treated K562 cells decreased with increased expressions of PARP in time-dependent manner. It is concluded that the emodin efficiently inhibits growth and induces apoptosis of K562 cells, while the inhibition of phosphorylation of P210 protein, down-regulation of P210 protein expression and activation of caspase-3 may be involved in these processes.
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PMID:[Effect of emodin on proliferation inhibition and apoptosis induction in leukemic K562 cells]. 2003 Sep 21

This study was purposed to explore the effect of specific small interfering RNA targeting at bcr-abl fusion gene and its combination with p27 gene clone on the proliferation, cell cycle and apoptosis of chronic myeloid leukemia (CML) cell line K562. CML cell line K562 was used as the study object. A 21nt siRNA targeting at the fusion site of b3:a2 mRNA in bcr-abl fusion gene was designed, synthesized and transfected into the K562 cells as RNA interference group. Northern blot was used to detect the bcr-abl fusion gene, Western blot was used to detect the expression of P210 protein and apoptosis-related protein BCL-xL after the transfection. Meanwhile, p27 gene was amplified from peripheral blood mononuclear cells by RT-PCR, and was confirmed to be correct by sequencing, then p27-pcDNA3.1 vector was constructed and transfected into K562 cell line by Lipofectin. After being selected with G418, p27-pcDNA3.1-K562 cell clone stably expressing p27 was isolated. P27 protein was identified by Western blot. Finally, siRNA and p27 gene clone were together applied to K562 cells, the cell survival rate was tested by MTT. The cell cycle and the apoptosis were tested by flow cytometry. The result showed that in contrast with the control group, the expression level of bcr-abl fusion gene was much lower in siRNA group, about 18.4% of K562 cells in siRNA group were apoptotic at 24 hours after siRNA transfection, and the expression of apoptosis-associated protein BCL-xL was greatly down-regulated. The expression of P27 protein could be detected by Western blot in p27-pcDNA3.1-K562 cells. The strong inhibition of cell proliferation was observed in p27-pcDNA3.1-K562 cells, as compared with control K562 cells. The count of p27-pcDNA3.1-K562 cells in G(0)/G(1) phase increased apparently, but that in S phase declined greatly. Cell cycle was arrested in G(0)/G(1) phase. After the combination of p27-pcDNA3.1-K562 cells with specific siRNA, the percentage of apoptosis obviously increased and cell survival rate significantly declined. It is concluded that the specific siRNA distinctly inhibits the expression of bcr-abl fusion gene, and can induce K562 cell apoptosis. The combination of specific siRNA with P27 gene clone displays a synergy of inhibition and pro-apoptosis effects to K562 cells.
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PMID:[Effects of specific siRNA targeting at bcr-abl fusion gene and its combination with p27 gene clone on chronic myeloid leukemia cell line K562]. 2056 11


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