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)

The BCR/ABL oncogene in chronic myelogenous leukemia produces an activated tyrosine kinase fusion protein (p210). Like other tyrosine kinase oncogenes, BCR/ABL can abrogate the interleukin-3 (IL-3) dependence of lymphoid cell lines. To investigate the ability of BCR/ABL to generate growth factor independence in myeloid cells, the IL-3 dependent myeloid cell line NFS/N1.H7 (H7) was transfected with the p210BCR/ABL-containing plasmid, pGD210. Stable clones A54 and A74 were capable of IL-3 independent growth and tumor formation in syngeneic mice. Relief of growth factor dependence was not mediated by autocrine release of IL-3. The baseline proliferation rate of the BCR/ABL transformed cells was greater than that of the parental H7 cells maximally stimulated by IL-3. Abundant constitutive expression of c-myc, c-jun, and c-fos was observed in the p210BCR/ABL transfectants even in low serum conditions. In contrast, c-myc expression in H7 cells was dependent upon IL-3 stimulation, and neither c-jun nor c-fos was highly expressed following IL-3 stimulation in H7 cells. Thus, BCR/ABL transformation and relief of IL-3 dependence involve not only pathways that can substitute for IL-3 induced growth via tyrosine kinase mediated signals, but also pathways that recruit constitutive c-jun and c-fos expression.
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PMID:BCR/ABL confers growth factor independence upon a murine myeloid cell line. 137 13

Concentration of circulating immune complexes (CIC) and cytotoxicity (natural and antibody-dependent) of blood lymphocytes were studied in 52 patients at the developed stage of chronic myeloid leukemia (CML). Elevation of CIC level and reduction of cytotoxicity detectable in all CML patients were most manifest in those with high tumor mass and during exacerbation of the leukemia process. A conclusion has been made that CIC are suppressors of natural and antibody-dependent cytotoxicity of blood lymphocytes in CML patients.
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PMID:[Suppressive effect of circulating immune complexes on cytotoxicity of blood lymphocytes in patients with chronic myeloid leukemia]. 142

A patient with CML showed monoblastic crisis which started with extramedullary tumor formation in a rib before medullary involvement. She was diagnosed as having CML in 1984 at the age of 57. In February 1990, she was admitted to Furukawa City Hospital because of extramedullary blastic crisis beginning at the right 5th rib. At that time, the bone marrow revealed 4.6% blasts. On March 5, after one course of chemotherapy, she was transferred to our hospital for radiotherapy. Hematological findings were WBC 10,100/microliter with 10% blasts, Hb 10.9 g/dl, platelet 3.7 x 10(4)/microliters. Bone marrow aspiration was unsuccessful. The blasts in the peripheral blood were negative for peroxidase and chloroacetate esterase; but positive for naphtylbutyrate esterase. The leukemic cells were positive for CD13, CD33, and had phagocytic activity. Chromosomal analysis revealed 46XX with Ph1 chromosome and some additional anomalies. Southern blot analysis of tumor cells shows BCR rearrangement. These findings suggest that the blasts were immature monocytic cells, and we conclude that this is a rare case of extramedullary monoblastic crisis of CML.
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PMID:[A case of monoblastic crisis of CML beginning with extramedullary tumor formation in a rib]. 143 21

Urinary excretion of parathyroid hormone-related protein (PTH-rP) was measured by radioimmunoassay in 25 patients with adult T-cell leukemia (ATL), in 68 patients with other hematologic disorders and in 13 asymptomatic individuals seropositive for human T-cell leukemia virus type I (HTLV-I). The mean levels of urinary PTH-rP in ATL patients with hypercalcemia (11.01 micrograms/g.Cr) were higher than in ATL patients with normocalcemia (5.16 micrograms/g.Cr). The mean levels in patients with acute type (8.84 micrograms/g.Cr), lymphoma type (4.18 micrograms/g.Cr) and crisis ATL (18.20 micrograms/g.Cr) were significantly higher than in urine of healthy controls. However, all asymptomatic carriers of HTLV-I and patients with chronic and smoldering ATL had normal urinary PTH-rP levels. In 7 patients with acute myelogenous leukemia, 1 patient with blastic crisis of chronic myelogenous leukemia and 3 patients with malignant lymphoma, the urinary levels of PTH-rP were above the normal range. Urinary levels of PTH-rP of the ATL patients with hypercalcemia correlated with the serum calcium levels. Urinary levels of PTH-rP of the all ATL correlated with serum lactic dehydrogenase level. These findings suggest that the measurement of urinary levels of PTH-rP is useful for evaluation of ATL and that some tumor cells of other hematologic diseases may produce PTH-rP.
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PMID:[Urinary excretion of parathyroid hormone-related protein in patients with adult T-cell leukemia and other hematologic disorders]. 143 36

A 42-year-old male was diagnosed as having Ph-positive chronic myelogenous leukemia (CML) in 1988. He had been treated with ranimustine and interferon alpha. In April 1990, he was admitted to our hospital because of hemorrhagic diathesis. Blood counts revealed a white blood cell count of 319,200/microliters with 12 per cent blasts, a hemoglobin level of 9.2 g/dl, and a platelet count of 48,000/microliters. The bone marrow aspiration revealed hypercellularity with 68.2 per cent blasts, and chromosomal analysis showed 48, XY, +8, double Ph. A combination chemotherapy containing vindesine, cytarabine and prednisolone was administered. Four days later, he suddenly complained of headache and vertigo. CT scan of the brain showed a high density area at the cerebellar vermis. He was then treated with intensive combination chemotherapy including enocitabine, daunomycin, 6-mercaptopurine and prednisolone. He attained a hematological response and clinical improvement temporarily, as the cerebellar tumor regressed. In September he had headache and vertigo again, and CT scan revealed a rapid increase in size of the cerebellar tumor. Local irradiation with total doses of 19 Gy brought about a partial resolution of the lesion, and relief from the symptoms. In November, his hematological conditions deteriorated gradually and he died of brain hemorrhage on November 22, 1990. Post-mortem examination disclosed a 1 x 1 cm sized mass in the cerebellar vermis which showed a fibrous change surrounded with hemosiderin-laden macrophages microscopically. We reviewed the eight reported cases of CML with intracranial tumors, and discussed the factors which had contributed to the prolongation of survival in our patient.
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PMID:[Isolated cerebellar tumor formation in a patient with blastic crisis of chronic myelogenous leukemia]. 143 48

The reciprocal translocation between chromosome 9 and chromosome 22, as observed in chronic myeloid leukemia (CML) as well as in acute lymphoblastic leukemia (ALL), results in a 22q- chromosome, the so-called Philadelphia chromosome. The translocation event creates on the Philadelphia chromosome a fusion between two genes: bcr and abl. Depending on the localization of the breakpoint in the bcr gene different chimeric bcr-abl genes are generated, each encoding their own tumor-specific protein: e1-a2P190bcr-abl, b2-a2p210bcr-abl, or b3-a2P210bcr-abl. Especially in ALL, the presence of such a tumor-specific protein is highly associated with a poor prognosis. Detection of these proteins therefore has a strong clinical significance. In this study a polyclonal antiserum, termed BP-2, was raised against a synthetic peptide, corresponding to the tumor-specific 'fusion-point' epitope of the b3-a2P210bcr-abl protein. The specificity of BP-2 for the bcr-abl joining region in b3-a2P210bcr-abl is demonstrated by means of peptide inhibition studies in combination with immunoprecipitation. In addition we show the reactivity of BP-2 with bcr-abl proteins in leukemic cells of a Philadelphia-chromosome-positive ALL patient.
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PMID:Antibody recognition of the tumor-specific b3-a2 junction of bcr-abl chimeric proteins in Philadelphia-chromosome-positive leukemias. 143 92

Ukrain is a semisynthetic compound consisting of alkaloids from Chelidonium majus L. conjugated to thiophosphoric acid, with immunomodulatory and therapeutic properties in cancer patients. The present in vitro studies demonstrate that Ukrain is an effective biological response modifier in that it augmented, by up to 48-fold, the lytic activity of spleen lymphocytes obtained from alloimmunized mice. The lytic activities of IL-2-treated spleen cells and peritoneal exudate lymphocytes were also increased significantly by the addition of Ukrain to the CML assay medium. The highest Ukrain-induced enhancement of spleen lymphocyte lytic activity in vitro was found to occur at 18 days after alloimmunization, was dose dependent and specific for the immunizing P815 tumor cells. Since Ukrain was present only during the CML assays, its mode of action is thought to be via direct activation of the effector cell's lytic mechanism(s).
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PMID:Activation of spleen cell lytic activity by the alkaloid thiophosphoric acid derivative: Ukrain. 146 76

The complement receptor 1 (CR1), also called CD35, is a polymorphic glycoprotein which mediates a variety of neutrophil functions, including phagocytosis and, probably, tumor cell cytotoxicity. The role played by this molecule in chronic myeloid leukemia (CML) is not yet well understood. CML frequently shows a marked decrease of CR1 antigens on both the neutrophil population and myeloid precursors. This reduced expression appears to be related to disease activity, since patients at more advanced clinical stages, as well as those who develop blastic crisis, have been found to express the lowest levels of CR1 antigens. At the onset of the disease low CR1 expression on CML neutrophils seems to be associated with a higher risk of blastic transformation. Furthermore, CML neutrophils deficient in CR1 lack the ability to respond to PMA stimulation, suggesting a failure in CR1 granular storage. In patients lacking CR1, the number of receptors increased to normal levels following exposure of CML cells to therapeutic concentrations of recombinant alpha interferon. The role played by the CR1 molecule in sustaining neutrophil-mediated tumor cell cytotoxicity has yet to be definitively proved; studies performed by our group are relevant here, since complete suppression of tumor lysis following receptor neutralization by anti CR1 monoclonal antibodies was demonstrated in a large number of normal and CML individuals. In CML patients, the evidence of a direct relationship between lytic activity and antigen receptor levels seems to further support the involvement of CR1 molecules in tumor cell lysis, function.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Complement receptor 1 (CR1) expression in chronic myeloid leukemia. 149 69

The p53 gene encodes a nuclear phosphoprotein and is now considered as a tumor suppressor gene. Mutations of the p53 gene have frequently been observed in several types of solid tumors and are believed to be implicated in the development of these tumors. Recent studies have shown that the p53 gene is altered in chronic myelogenous leukemia (CML) in blast crisis. In CML, alterations of the p53 gene may play an important role in the development of blast crisis. More recently, p53 mutations have been reported in other types of hematologic neoplasms, such as acute leukemia, adult T-cell leukemia, and malignant lymphoma. These observations suggest that inactivation of the p53 gene is involved in the tumorigenesis of various types of hematologic neoplasms.
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PMID:[Mutations of the p53 gene in hematologic neoplasms]. 151 57

In both animal models and human studies in leukemia, residual disease on day 8 following myelosuppressive therapy is in a proliferative phase and therefore may be sensitive to the S-phase specific drug cytarabine. Based on this concept, 17 patients with refractory or relapsed leukemia or lymphoma undergoing either autologous or allogeneic bone marrow transplantation (BMT) were treated on a Phase I protocol using high doses of busulfan (16 mg/kg, days -10, -9, -8, -7) and cyclophosphamide (120 mg/kg, days -6, -5) followed by escalating doses of a 48-h continuous infusion of cytarabine (starting dose 1000 mg/m2/48 h, days -3, -2). Ten patients received autologous transplants (two with Hodgkin's disease, seven with non-Hodgkin's lymphoma, one with chronic myelogenous leukemia (CML) in blast phase). Seven received allogeneic BMT (two with refractory acute myelocytic leukemia (AML), one with refractory acute lymphoblastic leukemia (ALL) undergoing a second BMT, one with Burkitt's-type leukemia, one with ALL in fifth relapse and two with CML in accelerated/blast phase). Two of these patients received a T cell-depleted haploidentical transplant. The maximum tolerated dose of cytarabine was 1500 mg/m2/48 h; a pulmonary syndrome including dyspnea, hypoxemia, and interstitial infiltrates which responded to aggressive diuresis was the dose limiting toxicity. Of the 10 patients who received cytarabine doses of 2000 or 2500 mg/m2/48 h, five patients developed adult respiratory distress syndrome (ARDS) with three patients requiring intubation; two recovered. Of the nine patients with lymphoma, seven responded with complete tumor clearance (CTC) with two patients tumor-free 13 and 15 months post-BMT, one remained refractory and one died too early to evaluate (TETE).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phase I study of busulfan, cyclophosphamide, and timed sequential escalating doses of cytarabine followed by bone marrow transplantation. 154 48


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