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

Activin A, one member of the transforming growth factor (TGF)-beta superfamily, is known to be a commitment factor for cell death and differentiation. In the present study, we demonstrate that human chronic myeloid leukemia (CML) cell lines, KU812 and K562 cells, either induced apoptosis or differentiation, respectively, by treatment with activin A. During these cell fate decisive events caused by activin A, rapid and transient up-regulation of Mcl-1 was observed in both cell lines. In activin A-induced apoptosis of KU812 cells, continuous up-regulation of Bax was observed. After the decrease in Mcl-1 expression had occurred, activation of caspase-9 and caspase-3 and cleavage of DFF45 were shown to take place in KU812 cells, resulting in the fragmentation of the genomic DNA of the cells. In contrast, the down-regulation of Mcl-1 without up-regulation of Bax caused accumulation of hemoglobin (Hb) contents in activin A-treated K562 cells. Interestingly, erythropoietin (EPO) prevented activin A-induced apoptosis with continuous expression of Mcl-1 and caused KU812 cells to undergo erythroid differentiation. To address the role of Mcl-1 in activin A-treated CML cells, KU812 and K562 cells were stably transfected with cDNA encoding Mcl-1 (designated as KU812/mcl and K562/mcl cells). As in combined effect of activin A and EPO on the parental KU812 cells, activin A induced differentiation, but not apoptosis, of KU812/mcl cells without modulating Bax levels. Activin A-treated K562/mcl cells, as well as parental cells, were only differentiated to erythroid cells. These results suggest that Mcl-1 is an early inducible gene activated by the activin A signaling pathway for both cellular differentiation and apoptosis, and continuous expression of Mcl-1 may be contributed to differentiation signals to the erythroid lineage in CML cells.
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PMID:Mcl-1, an early-induction molecule, modulates activin A-induced apoptosis and differentiation of CML cells. 1131 4

Scalarane-type sesterterpenes, PHC-1-PHC-7, which have been isolated from a marine sponge, increased hemoglobin production in human chronic myelogenous leukemia cell line K562 at the concentration of 0.1-5 microg/ml. PHC-1, the major constituent, induced the expression of glycophorin A and the enucleation for K562 cells. These sesterterpenes were found to induce erythroid differentiation in K562 cells. In addition, PHC-1 induced G1 arrest of the cell cycle of K562 cells.
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PMID:Differentiation in chronic myelogenous leukemia cell K562 by spongean sesterterpene. 1140 76

Priapism is an uncommon clinical symptom in children with chronic myelogenous leukemia (CML). Here we report a 14-year-old boy with this symptom, which had appeared 4 days prior to hospitalization. Peripheral blood examination revealed a leukocyte count of 510,000/microliter, (87% neutrophils, 3% eosinophils, 6% basophils, and 1.6% lymphocytes), a hemoglobin level of 6.5 g/dl and a platelet count of 640,000/microliter. Karyotype analysis revealed the Ph1 chromosome and myeloid hyperplasia in the bone marrow. The patient was diagnosed as having chronic myelogenous leukemia (CML) complicated by priapism. In an unsuccessful attempt to alleviate and improve the priapism, urokinase was injected and hydroxyurea was administered for the CML. Angiography confirmed the presence of venous return from the scrotum, and embolization of the bilateral internal pudendal arteries was performed to reduce the amount of inflow. Although this relieved the patient of his pain and prevented penile necrosis, the patient's future sexual potency was sacrificed. Selective embolization of the pudendal arteries can be one of the most effective ways of treating intractable priapism, if angiography confirms the presence of venous return from the penis.
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PMID:[Embolization of the bilateral internal pudendal arteries for intractable priapism in a child with chronic myelogenous leukemia]. 1180 81

A 73-year-old woman with chronic myeloid leukemia was treated with interferon-alpha, hydroxyurea, and busulfan before imatinib mesylate treatment. The leukocyte count was 8,400/; hemoglobin concentration, 12.0 g/; and platelet count, 19.7 x 10(4)/. She received 400 mg of imatinib mesylate for 17 days before the agent was discontinued because of pancytopenia. A bone marrow biopsy on the 87th day after the last imatinib mesylate administration demonstrated severe hypocellularity. She needed many RBC and Plt transfusions and filgrastim administration. Grade 4 neutropenia continued for 35 days and Grade 3 thrombocytopenia continued for over 122 days. Imatinib mesylate, an agent targeting BCR-ABL, is expected to be useful as an effective therapeutic agent for chronic myeloid leukemia. However the present case suggests that its appropriate dose is individually variable and we should carefully consider the former treatment, and the clinical stage of the disease before initiating imatinib treatment.
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PMID:[Chronic myeloid leukemia associated with sustained severe pancytopenia after imatinib mesylate therapy]. 1241 95

A 41-year-old woman, Philadelphia positive chronic myeloid leukemia patient, had progressive decline in hemoglobin levels. She had been receiving interferon alpha treatment for five years. Autoimmune hemolytic anemia was diagnosed. Subsequent bone marrow examination revealed translocation t(7;14). She was placed on prednisone treatment. The patient responded to prednisone as treatment for the hemolytic process. The result of a direct Coombs' test remained positive. The patient died shortly after the diagnosis of autoimmune hemolytic anemia. Autoimmune hemolytic anemia should be considered in the evaluation of chronic myeloid leukemia patients with a sudden decrease in hemoglobin levels.
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PMID:Autoimmune hemolytic anemia in Philadelphia positive chronic myeloid leukemia with t(7;14) anomaly after 5 years of interferon alpha treatment. 1241 37

A time-delayed fluorescence immunoassay was developed for the determination of serum levels of methylglyoxal (MG)-derived hydroimidazolone using a monoclonal antiserum raised against Nalpha-acetyl-Ndelta-(5-hydro-5-methyl)-4-imidazolone, Europium-labeled anti-mouse IgG antiserum as indicator, and MG modified bovine serum albumin (BSA) as standard. Serum levels of hydroimidazolone were measured in 45 patients with type 2 diabetes aged 59.4 +/- 6.1 (mean +/- SD) years and with duration of diabetes of 7.3 +/- 3.1 years, and in 19 nondiabetic controls aged 56.3 +/- 4.3 years. The serum levels of hydroimidazolone were significantly higher in patients compared to controls: median, 3.0 (5-95 percentile, 1.6 to 5.4) U/mg protein versus 1.9 (1.2 to 2.8) U/mg protein (P =.0005). Significant positive correlations were observed between the serum levels of hydroimidazolone and serum levels of advanced glycation end products (AGEs), measured with a polyclonal anti-AGE antibody: r = 0.59 for patients (P <.0001), and r = 0.65 for controls (P =.002). Similarly, significant correlations were also found between serum levels of hydroimidazolone and N(epsilon)-(carboxymethyl)-lysine (CML): r = 0.36 in patients and r = 0.55 for controls (both P =.02). Serum hydroimidazolone levels did not correlate with fasting plasma glucose or hemoglobin A(1c) (HbA(1c)) levels. The observed differences between patients with diabetes and nondiabetic controls seem to be comparable to differences measured for other AGE compounds.
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PMID:Increased serum levels of the specific AGE-compound methylglyoxal-derived hydroimidazolone in patients with type 2 diabetes. 1260 26

The acute lymphoblastic leukemia cell line CCRF-CEM is sensitive to Ara-C and undergoes apoptosis. In contrast, the chronic myelogenous leukemia (CML) cell line K562 is highly resistant to Ara-C, which causes the cells to differentiate into erythrocytes before undergoing apoptosis. We used cDNA microarrays to monitor the alterations in gene expression in these two cell lines under conditions leading to apoptosis or differentiation. Ara-C-treated CCRF-CEM cells were characterized by a cluster of down-regulated chaperone genes, whereas Ara-C-treated K562 cells were characterized by a cluster of up-regulated hemoglobin genes. In K562 cells, Ara-C treatment induced significant down-regulation of the asparagine synthetase gene, which is involved in resistance to L-asparaginase. Sequential treatment with Ara-C and L-asparaginase had a synergistic effect on the inhibition of K562 cell growth, and combination therapy with these two anticancer agents may prove effective in the treatment of CML, which cannot be cured by either drug alone.
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PMID:cDNA microarray analysis of altered gene expression in Ara-C-treated leukemia cells. 1295 Oct 57

We followed 141 patients treated with imatinib mesylate (> 300 mg) for chronicphase chronic myelogenous leukemia (CML) following failure of treatment with interferon. During 12 months from the start of imatinib mesylate treatment, 96.5% achieved a complete hematologic response, 47.0% achieved a major cytogenetic response, and 32.4% achieved a complete cytogenetic response. The proportion of patients with hematologic relapse was 10.9% at 12 months and 14.6% at 18 months. In a univariate Cox regression analysis, the only pretreatment characteristics that correlated with an increased risk of hematologic relapse were hemoglobin level less than 120 g/L (12 g/dL) (P =.02), increased bands in the peripheral blood (P =.01), and clonal evolution (P <.0001). In a multivariate analysis, an elevated platelet count (P =.03) and clonal evolution (P <.0001) were the only significant factors for hematologic relapse. During treatment, the absence of a major cytogenetic response within the first 6 months also significantly correlated with relapse (P =.03). Notably, patients failing to achieve a major cytogenetic response by 6 months had a significantly higher rate of hematologic relapse (27%) compared with those who achieved a major cytogenetic response by 6 months (3%), and patients with clonal evolution had a significantly higher risk of hematologic relapse (50%) than those without clonal evolution (9%).
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PMID:Clonal evolution and lack of cytogenetic response are adverse prognostic factors for hematologic relapse of chronic phase CML patients treated with imatinib mesylate. 1451 12

A 69-year-old man was found to have leukocytosis and a bleeding tendency, when he underwent surgery for hemorrhoids in November 1992, at the age of 69. The patient was referred to our department for further examination, and was admitted on December 4. On admission, he had hepatomegaly (5 cm) and splenomegaly (12 cm). Laboratory data on admission showed that the leukocyte count was 173,400/microliter, erythrocyte count, 314 x 10(4)/microliter, hemoglobin level, 10.5 g/dl, hematocrit value, 29.7%, and platelet count, 14.4 x 10(4)/microliter, respectively. Peripheral hemogram revealed neutrophilia with a shift to the left to promyelocytes, and the positivity of neutrophil alkaline phosphatase (NAP) was very low. The bone marrow was hyperplastic with a high M/E ratio (5.8). As the chromosome analysis revealed that he had 9:22 translocation in all 20 karyotypes, chronic myelogenous leukemia in the chronic phase, was diagnosed. After the daily intramuscular administration of 9 megaunits interferon alpha-2b was started on December 9, 1992, his leukocyte count stabilized between 5,000 and 8,000/microliter. Thereafter, intramuscular administration of IFN alpha has been continued regularly almost twice a week at the outpatient clinic until now. The leukocyte count ranges from 3,000 to 6,000/ml and he is asymptomatic. In April 1995, complete cytogenetic response was achieved 28 months after the start of interferon alpha therapy. The recent bone marrow chromosomes examination showed Philadelphia-negative metaphases until now, December, 2002, although major bcr-abl still remains positive. This case suggests that treatment with interferon alpha may still be useful in some elderly patients with chronic myelogenous leukemia.
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PMID:[Cytogenetic remission 10 years after the start of monotherapy with interferon alpha-2b in elderly chronic myelogenous leukemia]. 1457 25

STI571 is a specific tyrosine kinase inhibitor of Abl kinase. It was previously reported that STI571 induced hemoglobin synthesis in the chronic myelogenous leukemia (CML) cell line K562. However, its mechanisms remain unknown. In this study, we demonstrated that STI571 induced the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and dephosphorylation of extracellular signal-regulated kinase (ERK) in K562 cells. In contrast, the phosphorylation of c-Jun N-terminal kinases (JNK) in K562 cells was not altered by STI571. We also found that STI571 induced all the myeloid (CD11b, CD13), megakaryocytic (CD41a, CD42), and erythroid (glycophorin-A) markers on K562 cells. A p38 MAPK-specific inhibitor, SB203580, inhibited the STI571-induced multi-lineage differentiation of K562 cells, indicating that p38 MAPK is crucial for this differentiation. In contrast, SB203580 did not overcome the inhibitory effect for proliferation of K562 cells, indicating that p38 MAPK activation by STI571 does not affect cell numbers. Among the hematopoietic transcription factors, the expression level of c-myb mRNA was clearly downregulated after incubation with STI571 in K562 cells. STI571-induced downregulation of c-myb mRNA was prevented by the pretreatment of K562 cells by SB203580. Our data provides insights into how p38 MAPK and ERK pathways are involved in STI571-induced differentiation of K562 cells.
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PMID:Different roles of p38 MAPK and ERK in STI571-induced multi-lineage differentiation of K562 cells. 1475 42


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