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)

The presence of Philadelphia chromosome t(9:22) is a hallmark of 95% of clinical cases of chronic myelogenous leukemia (CML) as well as 20% of adult acute lymphoblastic leukemia (ALL) and 5% of acute myeloid leukemia (AML). The product of t(9;22) is a fusion protein BCR-ABL. The fusion proteins of CML, ALL and AML have increased tyrosine kinase activity and show a transforming potential in vitro and in animal models. The shorter p190 protein is associated almost only with ALL and AML, while the protein p210 is present in both chronic phase and blast crisis of CML and also in 50% of Philadelphia-positive (Ph1+) ALL. In CML the transition from chronic phase to blast crisis is usually accompanied by additional genetic events, e.g. additional chromosomal abnormalities, and oncogene activation(s). The detailed understanding of molecular basis of CML, and Ph1+ ALL and AML provides highly sensitive molecular and serological methods to complement classical cytogenetics. The advantages and limitations of these techniques are described and discussed below.
Tumour Biol 1990
PMID:Molecular pathology of chronic myelogenous leukemia. 224 53

The last decade has been very exciting for cancer cytogeneticists. At the start of the decade, the role of cytogenetics in clinical medicine was still unclear. Many felt that such investigations were largely of academic interest. Today, cytogenetic investigations are considered essential in many cancers, where they contribute in diagnosis, staging, choice of therapeutic protocol, and monitoring of the effects of therapy. The number of primary chromosome changes in human cancer exceeds 100, and while the majority of these changes are associated with haematological malignancies, the contribution from the solid tumours is now growing rapidly. Closer ties between scientists and physicians involved in laboratory and clinical medicine have resulted in the emergence of many well-defined cytogenetic-clinicopathological entities. With the advances in molecular biology that characterized the 1980s came the disappearance of all scepticism about the critical role played by chromosome change in oncogenesis. To date, we have learned more about the details of cancer biology in chronic myeloid leukaemia and the lymphoid malignancies through the molecular dissection of primary chromosome changes than through any other approach. Further studies will, no doubt, lead us to an understanding of the molecular basis of many of the primary and secondary chromosome changes that are non-randomly acquired in human cancer.
Tumour Biol 1990
PMID:Chromosome abnormalities in chronic myeloid leukaemia. A model for acquired chromosome changes in haematological malignancy. 224 54

Granulocytic sarcomas are rare manifestations of diseases of the white corpuscles. The incidence of this type of disease is not yet known because it is so rare. We observed two patients, who had had a chronic myeloid leukemia for several years, and in whom such a tumor occurred during the development of a blastomatous crisis. Both patients were examined by MRI. With this method it is possible to depict changes of the bone marrow as well as extramedullary lesions. MRI is a highly sensitive, but a less specific method.
 ...
PMID:[Chloroma in the blastic crisis of chronic myeloid leukemia--MR tomography findings]. 227 16

Neoplasia may develop in patients with malignant hematologic disorders, during remission after radio and/or chemotherapy. A multifactorial origin related to therapy may be postulated. From 1978 to 1987, among 142 patients with malignant hematologic disorders (Hodgkin lymphoma 33, non-Hodgkin lymphoma 51, Multiple Myeloma 35 and Chronic Myeloid Leukemia 31) we observed 3 patients developing another neoplasia. An additional patient with acute non-lymphatic leukemia had been submitted to chemotherapy for gastric cancer. Four other patients with double neoplasia, one of them a hematologic one, had not been submitted to chemotherapy. The lack of national registries for neoplastic diseases precludes an estimation of the odd ratios involved in our findings.
 ...
PMID:[Second neoplasms in malignant hematologic disorders. Experience from 1978 to 1987]. 196 10

Cytogenetic analyses were performed on 12 adult patients with abnormal megakaryoblastic proliferation which was detected by ultrastructural cytochemical study (platelet peroxidase) and platelet-megakaryocytes-specific monoclonal antibodies (TP-80, Plt1, AN51, and KOR-77). The patients consisted of two patients with myelodysplastic syndromes (MDS), three with acute megakaryoblastic leukemia (AMKL), six with megakaryoblastic transformation in Philadelphia-positive chronic myelogenous leukemia (CML-meg-BC), and one case of chronic myeloproliferative disorder (CMPD). Among them, an inversion of the long arm of chromosome 3 [inv(3)(q21q26)] was found in one AMKL patient with a normal platelet count. Chromosome change at band 3q26 was also found in one MDS patient without thrombocythemia. Furthermore, the long arm of chromosome 13, where rearrangements in myelofibrosis are clustered (13q12----q22) was seen in one MDS patient. Trisomoy of chromosome 19 was found in one AMKL patient and three CML-meg-BC patients. These findings indicate that cytogenetic abnormalities involving 3q26, 13q, and trisomy 19 are associated with hematologic neoplasia with megakaryocytic lineage in adult patients, although these abnormalities were not related to the survival of the patients. During the period of this study, two acute myelogenous leukemia patients (AML-M2 and AML-M5b) with chromosome rearrangements at band 3q21 and thrombocythemia were found, indicating that chromosome abnormality at band 3q21 is related to quantitative platelet dysfunction, whereas that at 3q26 is related to hematologic malignancies with a proliferation of megakaryocytic lineage.
 ...
PMID:Cytogenetic findings in adult acute leukemia and myeloproliferative disorders with an involvement of megakaryocyte lineage. 229 63

We describe a four-year experience with bone marrow transplantation involving closely HLA-matched unrelated donors and 55 consecutive patients with hematologic disease who were seven months to 48.6 years old (median, 18 years). An intensive pretransplantation conditioning regimen and graft-versus-host disease (GVHD) prophylaxis with CD3-directed T-cell depletion and cyclosporine were employed. Durable engraftment was achieved in 50 of 53 patients who could be evaluated (94 percent; 95 percent confidence interval, 83 to 98 percent). Acute GVHD of Grade II to IV developed in 46 percent of the patients (confidence interval, 27 to 66 percent). The incidence and severity of acute GVHD were increased in recipients of HLA-mismatched marrow as compared with recipients of phenotypically matched marrow (incidence of 53 percent [confidence interval, 37 to 68 percent] vs. 17 percent [confidence interval, 5 to 45 percent]; P less than 0.05). Extensive chronic GVHD and deaths not due to relapse also tended to be more frequent when HLA-mismatched marrow was used, but not significantly so. With a median follow-up of more than 19 months (range, greater than 9 to greater than 39), the actuarial disease-free survival of transplant recipients with leukemia and a relatively good prognosis (acute leukemia in first remission and chronic myelogenous leukemia in chronic phase) was 48 percent (confidence interval, 24 to 73 percent), and that of recipients with more aggressive leukemia was 32 percent (confidence interval, 18 to 51 percent); the actuarial survival of recipients with non-neoplastic disease was 63 percent (confidence interval, 31 to 86 percent). We conclude that marrow transplantation with closely HLA-matched unrelated donors can be effective treatment for neoplastic and non-neoplastic diseases. Although transplants from phenotypically HLA-matched unrelated donors appear to be most effective, transplants with limited HLA disparity can also be successful in some patients.
 ...
PMID:Successful allogeneic transplantation of T-cell-depleted bone marrow from closely HLA-matched unrelated donors. 230 Jan 20

The natural killer (NK) and lymphokine-activated killer (LAK) cell activities of peripheral blood lymphocytes from chronic myeloid leukemia (CML) patients in remission and from healthy donors have been studied. Regression analysis to compare both cytotoxic responses in individual donors and the frequency of LAK cell precursors was also carried out. About 42% of CML patients in remission showed low NK activity (less than the mean percentage NK activity of healthy donors--2 SD) and were categorised as low NK responders. The stage of remission or the drugs used to bring about remission did not influence the NK status. The LAK activity of low NK as well as normal NK responder CML patients was significantly low against the NK-sensitive K562 cell line and the NK-resistant VIP (melanoma) and T-24 (bladder carcinoma) tumor targets, as assessed by linear regression analysis. Allogeneic leukemic cells were more resistant to killing, especially by patients' LAK cells. The frequency analysis of LAK cell precursors revealed a significant reduction in the LAK cell progenitor frequency in CML patients in remission.
 ...
PMID:Natural killer and lymphokine-activated killer cell functions in chronic myeloid leukemia. 230 55

We present a patient with philadelphia chromosome (ph')-positive CML with extramedullary blast crisis in the lymph nodes before the bone marrow blast crisis. The morphological and cytochemical studies of lymph node touch preparation, and cytogenetic studies of lymph node tissue confirmed the extramedullary lymphoid blast transformation of CML, while the bone marrow continued to show the chronic phase of CML. When we changed our treatment to use Vincristine-Prednisolone therapy, the lymphadenopathy disappeared gradually. This case shows that the clinical and prognostic features of extramedullary disease can strongly affect disease acceleration in CML, and the therapy should be changed promptly. Besides, cytogenetic study of extramedullary tumor tissue in CML can be useful for accurate diagnosis.
 ...
PMID:Lymph node blast crisis of chronic myelogenous leukemia. One case report. 237 82

A 70-year-old patient is presented who, after chemotherapy for chronic myeloid leukaemia, developed two separate gastrointestinal malignancies. His family history indicated a strong family tendency towards neoplasia, and it is speculated that this predisposition may have been potentiated by the chemotherapy or the leukaemic process itself. It is stressed that, in such cases of multiple malignancy, each condition should be treated on its own merits.
 ...
PMID:Gastrointestinal malignancies as a complication of chronic myeloid leukaemia. 238 70

The possible presence of tumor cells in remission bone marrow (BM) is one of the major problems for the success of autologous BM transplantation (ABMT), because the reinfusion of viable malignant cells may result in relapse. In this study we attempted the purging of the malignant cells by the use of VP-16-213 (VP-16) and nitrogen mustard (NM) either alone or in combination. Four cell lines from various hematological malignancies were utilized: SK-DHL-2 was established from a B-cell diffuse histiocytic lymphoma; RAJI was from an Epstein-Barr virus (EBV)-infected B-cell lymphoma cell line; K-562 were from a chronic myelogenous leukemia (CML) blastic crisis; and HL-60, derived from a human promyelocytic leukemia, were used in exponential growth phase. Four logs of tumor cell-elimination were observed after 1-h incubation of RAJI cells with 25 micrograms/ml of VP-16. K-562 and SK-DHL-2 cells showed a greater than 4 logs reduction after 1-h exposure to 75 micrograms/ml of VP-16, and HL-60 cell line growth was inhibited by 3.2 logs. Under the same conditions (i.e., the treatment with 75 micrograms/ml), we observed a mean recovery of 2.7% of BM granulocyte-macrophage colonies (granulocyte-macrophage colony-forming units, CFU-GM), 3.2% of erythroid (erythroid burst-forming units, BFU-E), and 2.5% of pluripotent (granulocyte erythrocyte macrophage megakaryocyte colony-forming units, CFU-GEMM) progenitors, respectively. More than 3 logs reduction of leukemia and lymphoma cell lines were reached following 1-h treatment with 1 micrograms/ml of NM. After exposure to the same concentration of the drug we obtained 2.5% CFU-GM, 1.2% BFU-E, and 2% CFU-GEMM recovery. A drug mixture containing constant doses of VP-16 (10 and 20 micrograms/ml) and NM (1 micrograms/ml) reduced HL-60 and SK-DHL-2 cell growth to undetectable levels (i.e., 4 and 5 logs elimination) in the presence of an excess of irradiated BM cells, whereas it did not further affect the recovery of the BM precursors as compared to the single drugs used alone. These results suggest that the combination of these two drugs at the selected dose level could provide a better therapeutic index (i.e., higher tumor cell killing coupled with no additional cytotoxic effect on normal BM cells) than the same chemotherapeutic agent used alone and that this mixture may be useful for the "ex vivo" treatment of BM grafts.
 ...
PMID:In vitro cytotoxicity of VP-16-213 and nitrogen mustard: agonistic on tumor cells but not on normal human bone marrow progenitors. 239 48


<< Previous 1 2 3 4 5 6 7 8 9 10