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)

It has been suggested that abnormalities of chromosome 3 at bands q21 and q26 are associated with the presence of increased numbers of abnormal megakaryocytes in patients with hematologic malignancies. The pretreatment bone marrows of 287 patients with leukemia (acute myeloid leukemia (AML), 225 patients; acute lymphocytic leukemia (ALL), 36 patients; or chronic myelogenous leukemia in blast crisis (CML-B), 26 patients) were reviewed to identify those with normal or increased numbers of megakaryocytes. Thirty-two patients with AML, one with ALL, and 10 with CML-B had normal or increased numbers of megakaryocytes. Of the 32 patients with AML, 19 patients had significant numbers of mononuclear or binuclear small megakaryocytes as well as megakaryocytes with separated nuclei ("micromegakaryocytes"). Cytogenetic analyses were obtained in 29 of 32 patients with AML and showed inv(3)(q21q26) (one patient); Ph1 (two patients); -5 and/or -7 (seven patients); normal karyotypes (10 patients). No patient with micromegakaryocytes had a chromosomal abnormality associated with a favorable prognosis. Overall, among 225 patients with AML, four had inv(3)(q21q26) or t(3;3)(q21;q26). Only one of these four patients had normal or increased numbers of megakaryocytes, although all four had micromegakaryocytes. One patient with CML-B had inv(3)(q21q26) but had decreased numbers of megakaryocytes and a platelet count of 24 x 10(3)/microliters. All five patients with abnormal chromosome 3 at bands q21 and q26 had additional cytogenetic abnormalities (Ph1 in two patients; -7 in three patients). Mean and median platelet counts were greater than 100,000/microliters for patients with marrow megakaryocytosis regardless of morphology, as well as for the patients with abnormalities involving 3q21 and 3q26. Abnormalities of megakaryocyte morphology, increases in the numbers of megakaryocytes, and normal to increased platelet counts are not uncommon in patients with acute leukemia and CML-B, and are not uniquely associated with changes involving chromosome 3.
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PMID:Clinical and cytogenetic correlations of abnormal megakaryocytopoiesis in patients with acute leukemia and chronic myelogenous leukemia in blast crisis. 238 80

In tumor cells from virtually all patients with chronic myelogenous leukemia, the Philadelphia chromosome, a fusion of chromosomes 9 and 22, directs the synthesis of the P210bcr/abl protein. The protein-tyrosine kinase activity and hybrid structure of P210bcr/abl are similar to the oncogene product of the Abelson murine leukemia virus, P160gag/v-abl, which induces acute lymphomas. To determine whether P210bcr/abl can induce chronic myelogenous leukemia, murine bone marrow was infected with a retrovirus encoding P210bcr/abl and transplanted into irradiated syngeneic recipients. Transplant recipients developed several hematologic malignancies; prominent among them was a myeloproliferative syndrome closely resembling the chronic phase of human chronic myelogenous leukemia. Tumor tissue from diseased mice harbored the provirus encoding P210bcr/abl. These results demonstrate that P210bcr/abl expression can induce chronic myelogenous leukemia. Retrovirus-mediated expression of the protein provides a murine model system for further analysis of the disease.
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PMID:Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome. 240 2

Aspects and Results of Interferon Therapy Interferons are effector molecules with pleiotropic biologic functions. Significant clinical activities have been seen in viral diseases and hematologic malignancies, such as hairy cell leukemia, low-grade nodular non-Hodgkin's lymphoma, cutaneous T-cell lymphoma, and chronic myelogenous leukemia. In contrast, the efficacy in solid tumors has been less impressive. In these disorders, higher doses are necessary to induce remission. Responses to interferons are typically slow with improvement often taking several weeks to months. A wide range of both acute and chronic toxicities have been defined. Since these side effects are dose-related and are rarely tolerable for long-term treatment, optimal doses and schedules should be defined in future clinical trials. A better understanding of the mode of anticancer action is an important area of interferon research. Clinical areas might preferably include situations with minimal tumor load, especially in combination with other cytokines, different cytostatic drugs or local therapeutic modalities.
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PMID:[Various aspects and results of therapy with interferon]. 245 71

In the past decade, interferon, the first of a new class of biologic response modifiers, has undergone extensive Phase I and II clinical evaluation in a broad spectrum of cancers, including hematologic malignancies, lymphomas, and solid tumors. Interferon has been found to have important clinical activity in hairy-cell leukemia, low-grade non-Hodgkin's lymphoma, cutaneous T cell lymphoma, chronic myelogenous leukemia, previously untreated multiple myeloma, acquired immunodeficiency syndrome-related Kaposi's sarcoma, malignant carcinoid tumors, intravesically treated superficial bladder cancer, intraperitoneally treated ovarian carcinoma, renal cell carcinoma, and malignant melanoma. Recombinant DNA technology has produced molecules such as the interferons, which are antigenic and can induce antibody formation as part of a generalized immune response. The frequency of antibody occurrence, the magnitude of the antibody response, and the type of antibody induced by the interferons is thought to be related to several factors. These include the specific type of neoplasm for which interferon was administered; the specie of interferon administered; the dose, route, schedule, and duration of interferon administered; and the assay method and sampling time used to determine the antibody titer. Opinions and clinical observations about how these antibodies affect the clinical course of a disease vary among investigators. Some studies have demonstrated that antibody formation is associated with an abrogation of the clinical response, while others have not found any effects on the clinical course of a disease due to antibody presence.
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PMID:Biotherapy with interferon--1988. 246 49

The interferons are the first of a new class of biologic response modifiers that include, among others, the interleukins, colony-stimulating factors, erythropoietin, additional growth factors, and monoclonal antibodies. Interferons have exhibited important clinical activity in hematologic malignancies, lymphomas, and solid tumors. Specific diseases responding to interferons include hairy-cell leukemia (HCL), chronic myelogenous leukemia (CML), low-grade non-Hodgkin's lymphoma, cutaneous T-cell lymphoma, multiple myeloma, superficial bladder carcinoma, malignant carcinoid, acquired immunodeficiency syndrome (AIDS)-related Kaposi's sarcoma, ovarian carcinoma, renal cell carcinoma, and malignant melanoma. The potentially antigenic nature of the recombinant interferons can result in the formation of antibodies. These antibodies have been associated with the abrogation of some of the clinical responsiveness of some patients treated with interferons. It is hoped that the controversy existing over the role of antibody formation in treatment efficacy can be resolved by prospective trials using standardized methodology in such areas as assay type, sampling time, route of drug administration, treatment schedule, cumulative dose, and duration of treatment.
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PMID:Biotherapy in clinical practice. 247 4

Evaluation of double-stranded RNA by flow cytometric analysis is an important parameter for discriminating quantitatively between human tumoral and normal cells. We studied double-stranded RNA (ds-RNA) measurements using propidium-iodide after DNase treatment in bone marrow and in peripheral blood cells from patients with acute lymphoblastic leukemia, acute myeloid leukemia, chronic myeloid leukemia and multiple myeloma. The highest incidence of ds-RNA excess (greater than 30%) was observed in patients with acute leukemia (75%), while those displaying it in complete remission phase were 20-25% and in relapse about 80%. A high incidence was also noted in patients with chronic myeloid leukemia in blastic crisis (100%) and in patients with multiple myeloma with heavy tumor stage myeloma (78%). We never observed an elevated ds-RNA excess in the control group, formed by normal peripheral blood lymphocytes. Indeed the specificity of this tumor marker is attested to not only by its high levels in various hematologic malignancies, but also by its absence in normal cells. Hence the importance of its clinical implications in malignant hematologic diseases is confirmed.
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PMID:Double-stranded RNA excess in hematologic diseases: clinical implications. 263 84

Developments of oral mucosal ulcers induced by herpes simplex virus (HSV) were studied in patients with hematologic malignancy. Herpes simplex virus type-1 (HSV-1) was identified by immunological staining using virus-specific monoclonal antibodies in the epithelial cells of such ulcers from two patients with malignant lymphoma (ML), three with acute myeloblastic leukemia (AML), one with refractomy anemia with excess blasts, two with chronic myelocytic leukemia (CML), one with acute lymphoblastic leukemia (ALL) and one with aplastic anemia (AA). Herpes simplex virus type-2 (HSV-2) was also identified in an ulcer from a patient with AML. Isolation of HSV-1 was successful in the two patients with ML, one with CML, one with AML, the one with ALL and the one with AA. The ulcers developed on the tongue (four cases), buccal membrane (five cases), hard palate (one case), soft palate (one case), soft palate (one case) and gingiva (two cases). Only one patient with CML and one with AML had accompanying labial vesicular lesions. All patients except the one with AA had previously been given combination chemotherapy with anti-neoplastic agents. The results indicate that HSV may have an important role to play in the development of chemotherapy-related oral mucosal ulcers in patients with hematological malignancy.
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PMID:Herpes simplex virus in oral mucosal ulcers in patients with hematological malignancy. 255 41

Autocrine production of growth factors may contribute to the rapid and fatal proliferation of acute hematologic malignancies. We have investigated whether the more controlled growth of less aggressive malignancies such as chronic myeloid leukemia (CML) may be associated with autocrine production of growth inhibitory factors. TNF inhibits the growth of both normal and leukemic hemopoietic progenitor cells. We find that exogenous TNF reduces the viability and DNA synthesis of purified myeloid cells from patients with CML and inhibits myeloid colony formation by patient progenitor cells. However, unlike progenitor cells from normal donors, patient myeloid progenitor cells also constitutively express mRNA for TNF and secrete functional TNF protein in culture. This endogenous TNF impedes the growth of CML cells because anti-TNF mAb shown to neutralize bioactive human TNF increases CML cell DNA synthesis whereas non-neutralizing anti-TNF mAb has no effect. Production of TNF by CML cells is not associated with production of lymphotoxin (TNF-beta), IL-1 or IL-6. TNF-mediated autocrine growth inhibition may contribute to the maintenance of the stable, chronic phase of this disease and similar mechanisms may operate in other malignancies to limit tumor proliferation. Competition between autocrine growth promoting and inhibiting factors may underlie the observed differences in biologic behavior between acute and chronic malignancies.
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PMID:Tumor necrosis factor mediates autocrine growth inhibition in a chronic leukemia. 258 19

Bone marrow transplantation (BMT) offers potentially curable treatment for patients with high-risk hematologic malignancies. However, relapse remains the major cause for failure of autologous BMT in these diseases and of allogeneic BMT in subsets of patients with these diseases. With our current preparative regimens, relapse rates following autologous BMT are over 30% for patients with intermediate or high-grade non-Hodgkin lymphoma and relapsed Hodgkin's disease in sensitive relapse and over 50% following autologous BMT for patients with acute non-lymphoblastic leukemia (ANLL) and acute lymphoblastic leukemia (ALL). Relapse rates exceed 80% in patients treated with autologous BMT for non-Hodgkin lymphomas and Hodgkin's disease in drug-resistant relapse. We also see a relapse rate over 50% in patients given allogeneic BMT for ANLL in second or third remission or early relapse, for ALL in third or subsequent remission or early relapse, and for chronic myelogenous leukemia (CML) in accelerated phase or blast crisis. We have explored two new approaches for improving the anti-tumor activity of our BMT preparative regimens. One involves combining etoposide, a chemotherapeutic agent that has excellent activity against leukemias and lymphomas, has shown synergistic activity with cyclophosphamide in vitro, and can be substantially dose-escalated, with busulfan and cyclophosphamide. The other approach attempts to induce graft-versus-host disease (GVHD), which appears to provide a clinical anti-tumor effect following allogeneic BMT, in recipients of autologous BMT. A syndrome similar to mild GVHD has been reported to occur spontaneously in a small number of patients receiving autologous or syngeneic transplants. GVHD can also be induced in rats undergoing syngeneic BMT by treatment with cyclosporine (CSA).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:New conditioning regimens for high risk marrow transplants. 262 18

Etoposide, an epipodophyllotoxin structurally related to vincristine, is active in solid tumors. Trials of etoposide in hematologic malignancies, particularly leukemia and lymphoma, were initiated in 1973. Subsequent studies indicate that etoposide, either as a single agent or in combination with other drugs, is active in acute myelogenous leukemia, non-Hodgkin and Hodgkin lymphoma. Etoposide may be effective in acute lymphoblastic leukemia, but it is inactive in chronic myelogenous leukemia. The major toxicity of etoposide is myelosuppression. Non-hematologic toxicity is relatively mild at doses up to 2000 mg/m2. This feature favors its use in high dose regimens such as those employed before bone marrow transplantation. Preliminary studies of etoposide in autologous bone marrow transplantation in lymphoma and Hodgkin disease are promising. Studies of high dose etoposide in combination with other chemotherapeutic agents or in the context of bone marrow transplantation are in progress.
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PMID:Etoposide in leukemia, lymphoma and bone marrow transplantation. 267 26


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