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)

Thymidylate kinase derived from the blast cells of human chronic myelocytic leukemia was purified 2186-fold to near homogeneity by means of alcohol precipitation, alumina-Cgamma gel fractionation, calcium phosphate gel fraction, ultrafiltration, and affinity column chromatography. The molecular weight was estimated by glycerol gradient centrifugation to be 50,000. This enzyme had an optimal activity at pH 7.1 and required a divalent cation in order to catalyze the reaction. Mg2+ and Mn2+ were found to be the preferential divalent cations. The activation energy was estimated to be 19.1 kcal/mol at pH 7.2. Initial velocity study suggested that the reaction followed a sequential mechanism. Mg2+ ATP had a Km of 0.25 mM and dTMP had a Km of 40 micrometer. The enzyme was unstable even at 4 degrees. In the presence of ATP or dTMP the enzyme maintained its activity. Purine triphosphate nucleosides were found to be better phosphate donors than the pyrimidine triphosphate nucleosides. ATP and dATP had a lower Km and a higher Vmax than GTP and dGTP. dTMP was the only preferred phosphate receptor among all the monophosphate nucleotides tested dTTP and IdUTP competed with both substrates and inhibited the reaction with a Ki of 0.75 mM and 1.1 mM, respectively.
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PMID:Human thymidylate kinase. Purification, characterization, and kinetic behavior of the thymidylate kinase derived from chronic myelocytic leukemia. 1 69

During 59 periods of hospitalisation, 39 patients with either acute myeloid leukemia (22), acute lymphatic leukemia (9), acute undifferentiated leukemia (1), blastic crisis of chronic myeloid leukemia (6) or high-grade malignant non-Hodgkin lymphoma (1) were subjected to aggressive polychemotherapy after selective decontamination of the gut. The patients were given an amphotericin B suspension in a dosage of 1.2 g/day for two days, after which one tablet of trimethoprim/sulphamethoxazole (TMP/SMZ) (160 mg TMP and 800 mg SMZ) t.i.d. was added to prevent endogenous infections by gram-negative aerobic bacteria or moulds and to maintain the "colonisation resistance" endowed by the anaerobes. During 16 of the 59 periods of hospitalisation, no potentially pathogenic aerobic bacteria were isolated. TMP/SMZ-resistant Escherichia coli were the etiological agent of septicemia in two patients, and resistant Klebsiella pneumoniae and Pseudomonas aeruginosa in two other patients. These bacteria were cultured from the patients' fecal samples prior to the development of septicemia. We observed that long-term prophylaxis with TMP/SMZ modified the normal aspect of the fecal biotop culture, not only by suppressing the aerobic gram-negative bacteria, but also by allowing certain clostridia to appear. We differentiated 207 clostridia from the fecal samples of 29 patients and observed a predominance of TMP/SMZ-resistant Clostridium difficile, Clostridium innocuum and Clostridium clostridiiforme. C. difficile was also isolated from the blood culture of a neutropenic patient treated with TMP/SMZ and proved to be very toxic in the Verocell culture.
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PMID:The "clostridial effect" of selective decontamination of the human gut with trimethoprim/sulphamethoxazole in neutropenic patients. 635 9

Antisense oligodeoxyribonucleotides (ODNs) are now being extensively investigated in an attempt to achieve cell growth suppression through specific targeting of genes related to cell proliferation, despite increasing evidence of non-antisense cytotoxic effects. In the context of anti-BCR/ABL antisense strategies in chronic myeloid leukemia, we have reexamined the antiproliferative effect of phosphodiester and phosphorothioate ODNs on the leukemic cell line BV173 and on CD34+ bone marrow cells in liquid culture. The 3' sequences of the ODNs determine their effect. At concentrations of 10 micromol/L (for phosphorothioate ODNs) or 25 micromol/L (for phosphodiester ODNs), all the tested ODNs exert an antiproliferative activity, except those that contain a cytosine residue at either their two most terminal 3' positions. We show that this antiproliferative effect is due to the toxicity of the d-NMPs (5' monophosphate deoxyribonucleosides), the enzymatic hydrolysis products of the ODNs in culture medium. The toxicity of the d-NMPs on hematologic cells depends on their nature (d-CMP [2'deoxycytidine 5'-monophosphate] is not cytotoxic), on their concentration (d-GMP [2'-deoxyguanosine 5'-monophosphate], TMP [thymidine 5'-monophosphate], and d-AMP [2'-deoxyadenosine 5'-monophosphate] are cytotoxic at concentrations between 5 and 10 micromol/L), and on the coincident presence of other d-NMPs in the culture medium (d-CMP neutralizes the toxicity of d-AMP, d-GMP, or TMP). The antiproliferative activity of ODNs is thus restricted to conditions where the 3' hydrolysis process by exonucleases generates significant amounts of d-NMPs with a low proportion of d-CMP. Our results reveal a novel example of a nonantisense effect of ODNs, which should be taken into account when performing any experiment using assumed antisense ODNs.
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PMID:Antisense oligodeoxyribonucleotides suppress hematologic cell growth through stepwise release of deoxyribonucleotides. 920 69

We describe a case of pulmonary nocardiosis in a female patient with graft-versus-host disease (GVHD) underwent therapy with imatinib mesylate for a relapse of chronic myeloid leukemia (CML) after allogeneic bone marrow transplantation (BMT). The patient developed chronic GVHD 8 months after the use of imatinib and was on corticosteroid therapy. Three months after the development of chronic GVHD, she acquired pulmonary nocardiosis and a computed tomography (CT) scan of the chest showed multiple nodular lesions with cavitations over both lungs. She was successfully treated with single-agent trimethoprim-sulfamethoxazole (TMP/SMX) and the infection did not recur. Our case indicated that pulmonary nocardiosis could occur in patients with GVHD undergoing imatinib and corticosteroid therapy and might be treated by single-agent TMP/SMX.
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PMID:Pulmonary nocardiosis in a patient with CML relapse undergoing imatinib therapy after bone marrow transplantation. 1468 32

Rhabdomyolysis, a syndrome of muscle necrosis, is a life-threatening event. Here we describe the case of a patient with chronic myeloid leukemia who underwent a haploidentical stem cell transplant and subsequently developed rhabdomyolysis after beginning trimethoprim-sulfamethoxazole (TMP/SMX) prophylaxis therapy. Rechallenge with TMP/SMX resulted in a repeat episode of rhabdomyolysis and confirmed the association. Withdrawal of TMP/SMX led to sustained normalization of creatine kinase levels in the patient. A high index of suspicion is necessary to identify TMP/SMX as the cause of rhabdomyolysis in immunocompromised patients.
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PMID:Rhabdomyolysis due to Trimethoprim-Sulfamethoxazole Administration following a Hematopoietic Stem Cell Transplant. 2655 99