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)

We have developed a polymerase chain reaction (PCR) based technique to detect allelic loss. In this differential PCR a target gene and a reference gene are coamplified in the same reaction vessel. The ratio of the intensity of the two resultant bands is an indication of relative gene dosage. This procedure is sensitive in that gene copy ratios of 2:1 and 3:2 (reference: target gene) can readily be detected. Using this differential PCR, we have examined 64 cases of chronic myelogenous leukemia (CML) for the loss of the beta 1-interferon gene, a relatively common event in certain human leukemias and lymphomas. Only one patient who was Philadelphia chromosome positive and who was in blast crisis exhibited allelic loss of the beta-interferon gene. Thus despite deletions at the beta-interferon locus in the CML cell line, K562, this perturbation is rarely seen in primary CML samples.
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PMID:Polymerase chain reaction based assay to detect allelic loss in human DNA: loss of beta-interferon gene in chronic myelogenous leukemia. 231 49

Studies have shown that recombinant human alpha interferon (rIFN alpha) inhibits the growth of colonies of multipotential stem cells from human bone marrow. This report demonstrates that rIFN alpha inhibits the growth of such colonies from the bone marrow of patients with chronic myelogenous leukemia (CML) to a greater extent than from bone marrow of healthy individuals. It also shows that T lymphocyte colonies subcloned with interleukin 2 (IL-2) from CML mixed colonies were inhibited more by rIFN alpha than were similar colonies subcultured from normal mixed colonies. The report demonstrates that the Ph' chromosome is present in such T cell colonies subcultured from CML mixed colonies. When mixed colonies were grown from CML bone marrow in the presence of rIFN alpha, Ph' negative colonies were observed, whereas no such Ph' negative mixed colonies grew from a similar number of bone marrow cells incubated without rIFN alpha. These observations confirm that T lymphocytes derived from bone marrow stem cells are from the CML clone, and that the inhibition of growth of Ph' positive colonies, by rIFN alpha permits the growth of residual normal stem cells. The disappearance of the Ph-chromosome in subclones of T lymphocytes supports the notion of nonclonal hematopoiesis in patients with CML.
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PMID:Restoration of nonclonal hematopoiesis in chronic myelogenous leukemia with interferon alpha. 235 May 91

Eighteen chronic myeloid leukemia patients with hematological (four patients) or only cytogenetic (14 patients) relapse occurring after T cell-depleted allogeneic bone marrow transplantation (BMT) have been treated with alpha 2b interferon (IFN) at a starting dose of 5 x 10(6) i.u./m2 subcutaneously three times a week. All four patients with hematological relapse achieved long-lasting hematological remission without reduction of bone marrow Ph1 positive cells. When IFN was started the median percentage of bone marrow Ph1-positive metaphases was 50% (range 9-100) for the 14 patients with cytogenetic relapse. Twelve (85.7%) of these patients are alive with a median follow-up of 25 months (range 20-37 months) from cytogenetic relapse and 33 months (range 27-49 months) from BMT. Six (43%) of the 14 patients progressed to hematological relapse and eight patients (57%) are still in hematological remission with two patients achieving complete cytogenetic remission confirmed at molecular level by disappearance of the M-BCR rearranged band. IFN therapy may be a good alternative to conventional chemotherapy for transplanted CML patients with hematological relapse and the treatment of choice for patients with a persistent cytogenetic relapse occurring after T cell-depleted BMT.
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PMID:Interferon therapy for Ph1 positive CML patients relapsing after T cell-depleted allogeneic bone marrow transplantation. 209 16

We sought evidence of BCR/ABL transcripts in the peripheral blood of nine CML patients in complete clinical and cytogenetic remission after treatment by bone marrow transplantation (BMT) or interferon and in one patient who entered spontaneous remission. Six patients were investigated at different times during their follow-up. We compared results obtained with the polymerase chain reaction (PCR) using (a) a single-stage PCR comprising 30 cycles of amplification with selected oligomers, and (b) a two-stage procedure in which the reaction product from the first stage was subjected to a further 30 cycles with nested amplimers. Special care was taken to assess contamination, including for each patient simultaneous co-extraction of a negative control. Blood cells from all patients showed no evidence of BCR/ABL transcripts in the one-stage PCR but 9/17 specimens were positive in the two-stage procedure. Patients in complete remission for a long time (greater than 2 years) appeared negative. These results serve in part to explain the discordant findings reported in other studies and emphasize the importance of carefully selecting the technical conditions most likely to give results that are prognostically relevant for individual patients.
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PMID:Detection of residual BCR/ABL transcripts in chronic myeloid leukaemia patients in complete remission using the polymerase chain reaction and nested primers. 238 69

Cytoplasmic protein extracts from chronic myelogenous leukemia (CML) cells contained an activity that altered the electrophoretic mobility of complexes formed between nuclear proteins and the transcriptional enhancers of interferon (IFN)-inducible genes. Exposure of CML cells to IFN-alpha diminished the effect of the CML cytoplasmic proteins on these nuclear protein-DNA complexes. The presence of clinical responsiveness to IFN-alpha correlated with the sensitivity to the IFN-induced change in the electrophoretic mobility of nuclear protein-DNA complexes. These data suggest that the action of IFN-alpha in CML may be linked to a pathway that can result in posttranslational modification of nuclear proteins.
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PMID:Interferon affects nuclear proteins in cells of clinically sensitive chronic myelogenous leukemia patients. 240 Aug 7

Recent advances in the pathogenesis and treatment of chronic granulocytic leukemia (CGL) are reviewed. Three major phases of CGL are recognizable: the presymptomatic phase, the chronic phase, and the metamorphosis. The molecular dissection of the Philadelphia chromosome has revealed that this translocation activates the c-abl oncogene by fusion with another gene called bcr whose function is as yet unknown. Although almost all patients with CGL still succumb within 10 years of diagnosis, alpha-interferon and allogeneic bone marrow transplantation represent promising newer therapeutic developments. In particular, marrow transplantation appears to have curative potential in CGL.
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PMID:Chronic granulocytic leukemia: the devastating consequences of genetic instability. 242 7

Since the late 1970s, 18 clinical studies have been conducted in Japan with various types of human interferon (IFN) for their possible anti-tumor efficacy under the control of the Special Committee for Clinical Application of IFN of the Ministry of Health and Welfare. Objective antitumor effects have been observed in renal cell carcinoma, brain tumor, multiple myeloma, malignant lymphoma, adult T cell leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, and by local injections in skin cancer such as malignant melanoma and cutaneous lymphoma. In this paper, updated results of clinical studies of the 3 types of IFNson various malignant tumors in Japan was reviewed, and the potential usefulness of IFNs as the first cytokine introduced into a clinical trial of the treatment of cancer was discussed.
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PMID:[Clinical studies on interferon in cancer therapy in Japan]. 243 62

Compared to single-agent therapy with hydroxyurea or myleran (155 patients), intensive chemotherapy with vincristine, cytosine arabinoside, prednisone and cyclophosphamide (60 patients) or anthracyclines (37 patients) showed significant survival improvement overall (p less than 0.01) and among intermediate- and high-risk patients. Of 51 patients treated with human leukocyte alpha interferon (IFN-alpha), 36 (71%) had complete hematologic remission (CHR); 20 patients (39%) showed Ph suppression which was persistent in 13 for greater than 21 months. Survival was better in patients obtaining remission with IFN-alpha. Recombinant gamma interferon (IFN-gamma) was also active in chronic myelogenous leukemia. Therapy with combined IFN-alpha + IFN-gamma has been initiated. Compared to the expected survival, the observed survival is favorable for IFN-alpha and the combined chemotherapy and IFN-alpha programs. Future therapeutic trials will incorporate initial IFN therapy followed by cyclic intensive chemotherapy at 6-month intervals and IFN maintenance between chemotherapy cycles.
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PMID:Intensive combination chemotherapy and interferons in the management of chronic myelogenous leukemia. 244 26

Chronic myelocytic leukaemia is a myeloproliferative syndrome with two highly specific characteristics: it has a cytogenetic clonal marker known as Philadelphia chromosome and a molecular marker in the form of bcr-abl rearrangement, and it progresses in two phases: a chronic phase followed by an acute terminal phase of blastic transformation. The fatal outcome of this blood disease can only be checked if we possess one or several treatments providing a complete and stable clinical, haematological and cytogenetic remission. Such a course is seldom observed. The conventional treatment of the chronic phase consists of single drug chemotherapeutic regimens which have succeeded in increasing the patients' median survival but do not prevent blastic transformation which is beyond therapeutic resources. In some cases multiple drug chemotherapy, and notably bone marrow transplantation, may result in disappearance of the Philadelphia chromosome and arrest of the natural course of the disease. Interferon is a new treatment which eradicates the Philadelphia chromosome and offers hopes of complete and prolonged, if not permanent, remissions. The present experience, although limited, suggests that alpha-interferons are effective. Judging from the available data, it is very likely that the future treatment of myelocytic leukaemia will consist of chemotherapy combined with interferon(s) with or without bone marrow transplantation.
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PMID:[Does the Philadelphia chromosome disappear after treatment with interferon?]. 245 50

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


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