Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A serious limitation of chemotherapy for acute myeloid leukaemia (AML), Hodgkins disease and some classes of breast cancer is that, even when clinically evident disease responds well, the same chemotherapy when given during remission does not affect the rate of relapse after chemotherapeutic or surgical ablation of the primary disease. This cannot, in general, be caused by genetic adaptation of the residual cancer cells which renders them resistant to specific drugs, because after relapse further remissions can be obtained with the same drugs that were ineffective by chronic administration in prolonging remission. The resistance of the residual cells may arise from mechanisms such as inaccessibility for anatomical or other reasons, or because of a change in metabolic state which causes these cells temporarily to cease division, when they cannot be harmed by cycle-dependent drugs and repair damage sustained from cycle-independent drugs. Limited differentiation has been shown capable of reversal and this may be a mechanism which leads to quiescence and associated "resistance", particularly in the case of AML. Where such resistance occurs treatment during remission-or as an adjuvant to surgery and radiotherapy-may have to rely on mechanisms which are independent of cellular proliferation such as processes associated with graft-versus-host-disease or the induction of terminal differentiation. A model for studying the nature of resistance of residual cancer and for testing treatments that might be active against cancer cells in this state may be dormant metastases. The latter are malignant cells which appear to be in peaceful co-existence with their host and which in experimental systems have been induced to grow into lethal metastases by perturbation of the host by surgical trauma, by hormonal manipulation or by immunosuppression.
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PMID:2nd Gordon Hamilton Fairley lecture. Need for new approaches to the treatment of patients in clinical remission, with special reference to acute myeloid leukaemia. 696 Sep 22

Bone marrow chromosome studies were done on three patients who developed acute nonlymphocytic leukemia 5 to 19 months after completion of adjuvant chemotherapy for breast cancer, and on 17 breast cancer patients without hematologic disease 2 to 30 months after similar adjuvant therapy. Clones of cells with multiple cytogenetic abnormalities were demonstrated in two of the three leukemic patients. No chromosomally abnormal clones or evidence of increased chromosome damage was found in the 17 nonleukemic individuals. Although leukemias induced by chemotherapy, and particularly by alkylating agents, typically show multiple cytogenetic alterations, it appears that patients recently exposed to these agents, but without obvious hematopoietic disorders, do not have a high frequency of aberrant marrow clones. Additional approaches may be needed for early identification of patients at increased risk for chemotherapy-induced leukemia.
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PMID:Cytogenetic studies of bone marrow in breast cancer patients after adjuvant chemotherapy. 724 94

We have utilized a recently developed human tumor cloning system to screen for antitumor effects in vitro of a new anthracene derivative, CL216,942. The object was to determine whether the system is useful for pinpointing the types of tumors in patients which should be studied in early phase II clinical trials. Tumors from 684 patients were placed in culture (27 different histologic tumor types). Two hundred seventy-three tumors both grew and formed enough colonies for drug sensitivity assays. In vitro antitumor activity was noted for CL216,942 against human breast cancer, ovarian cancer, renal cancer, squamous cell, small cell and large cell lung cancer, lymphoma, acute myelogenous leukemia, melanoma, adenocarcinoma of unknown origin, adrenal cancer, gastric cancer, pancreatic cancer, and head and neck cancer. The drug definitely showed no in vitro activity against colon cancer. These data indicate that CL216,942 has a wide spectrum of in vitro antitumor activity. A comparison of these in vitro results with the results of phase II clinical trials with the drug should allow an evaluation of the utility of the human cloning system for predicting clinical activity of a new compound.
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PMID:Activity of 9-10 anthracenedicarboxaldehyde bis[(4,5-dihydro-1 H-imidazol-2-yl)hydrazone]dihydrochloride (CL216,942) in a human tumor cloning system. Leads for phase II trials in man. 730 32

Epidemiological and experimental studies concerning extremely low frequency electromagnetic field exposure and malignant diseases published up to 1 July 1994 were evaluated to assess the possible carcinogenicity of electromagnetic fields and the scientific basis for environmental and occupational standard setting. We concluded that there are possible associations between (i) an increased risk of leukaemia in children and the existence of, or distance to, power lines in the vicinity of their residence, (ii) an increased risk of chronic lymphatic leukaemia and occupational exposure to low frequency electromagnetic fields and (iii) an increased risk of breast cancer, malignant melanoma of the skin, nervous system tumours, non-Hodgkin lymphoma, acute lymphatic leukaemia or acute myeloid leukaemia and certain occupations. There is no scientific basis for occupational or environmental standard setting for low frequency electric or magnetic fields.
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PMID:Exposure to extremely low frequency electromagnetic fields and the risk of malignant diseases--an evaluation of epidemiological and experimental findings. 749 33

Twenty-eight patients with poor prognosis acute myeloid leukemia (AML) received therapy with two courses of fludarabine 30 mg/m2/day + ara-C 2 g/m2/day (days 1-5) and G-CSF 5 mg/kg/day (FLAG) (from day 0 to polymorphonuclear recovery). Eighteen patients were considered 'refractory' (eight primarily resistant, five relapsing within 6 months of initial remission, or at a second relapse; five relapsing after an autologous bone marrow transplantation procedure. Ten cases were defined 'secondary' AML (diagnosis of AML made after a preexisting diagnosis of: myelodysplastic syndrome: five cases; myelodysplastic syndrome after therapy for breast cancer: one case; previously untreated, and concomitant, non-Hodgkin's lymphoma: two cases; Hodgkin's disease treated with chemoradiotherapy: one case). Overall, 15 patients (58%) achieved a complete remission (CR). Two patients died of infection during induction, and 11 had resistant disease. Analyzing the data in relation to selected host and disease characteristics, the response varied widely. The highest CR rates (89%) were obtained in secondary AML; in particular, two cases of 'second-primary' (concomitant with low-grade non-Hodgkin's lymphoma) AML obtained CR for both diseases. Refractory AML differed widely for response: high CR rate (75%), although with short mean CR duration for primary resistance AML, and very poor response (11% CR) for relapsed (early, second, after ABMT) cases. Interestingly, a slow kinetic of leukemic growth in vivo before FLAG administration was significantly related to the response and outcome (p = 0.0002). Hematological and nonhematological toxicities were acceptable. In conclusion, the FLAG regimen has significant antileukemic activity and acceptable toxicity especially in secondary AML, both with and without coexisting lymphoid malignancy.
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PMID:FLAG (fludarabine + high-dose cytarabine + G-CSF): an effective and tolerable protocol for the treatment of 'poor risk' acute myeloid leukemias. 752 88

The human tri-thorax gene (HRX) also called ALL-1 (Acute Lymphocytic Leukemia-1) as well as MLL (Myeloid-lymphoid or Mixed-lineage Leukemia) gene, is disrupted in the majority of leukemias with chromosomal abnormalities involving 11q23. The alteration of the gene is related to leukemogenesis of various types such as acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), and acute mixed lineage leukemia. The gene is also rearranged in cases of secondary AML developing after exposure to chemotherapeutic agents, especially topoisomerase II inhibitors. In at least one report, genomic analysis of this recombination site showed the breakpoint to be a topoisomerase II binding site and that exposure to the inhibitor could induce the rearrangement. If exposure induces the rearrangement of the gene, secondary ALL as well as secondary AML could occur after exposure to these agents, because the type of leukemias with rearranged HRX gene is not limited to AML. We present here such a case of secondary ALL with this gene rearrangement which occurred during adjuvant chemotherapy for breast cancer. Although less cases of secondary ALL are reported in comparison with those of secondary AML, such case reports have been accumulating. The incidence of this type of leukemia should be clarified in the future.
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PMID:HRX gene rearrangement in secondary acute lymphoblastic leukemia. 754 29

Two major classes of therapy-related acute myeloid leukemias (t-AML) and myelodysplastic syndromes (t-MDS) have been described following the use of conventional doses of alkylating agents and epipodophyllotoxins. They are characterized by distinct clinical presentations and chromosomal abnormalities. We report 2 cases of t-AML and 1 case of t-MDS in 3 out of 36 women who underwent high-dose chemotherapy and attempted ABMT for breast cancer. Two patients developed t-AML 4 and 8 months following the initiation of high-dose chemotherapy with or without ABMT. The third patient developed t-MDS 23 months following dose-intensive chemotherapy and ABMT. Cytogenetic studies of the marrow metaphase chromosomes from the two patients who developed t-AML, including FISH analysis in 1 patient, showed a t(9;11)(p22ng,q23) abnormal chromosome 6 (ring chromosome). Neither patient had a preleukemic phase. Cytogenetic studies from the third patient who developed t-MDS showed abnormalities of chromosome 5 (-5) and a derivative of chromosome 17. The use of multiple chemotherapeutic agents in all 3 patients makes it difficult to attribute the development of these cases of t-MDS/t-AML to a single chemotherapeutic agent. The possible role of dose-intensive chemotherapy in the development of these secondary malignancies is discussed.
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PMID:Acute myeloid leukemia and myelodysplasia following intensive chemotherapy for breast cancer. 758 Nov 17

Techniques to assay minimal residual disease are available for most patients with acute lymphoblastic leukemia, non-Hodgkin's lymphoma, breast cancer, Ewing's sarcoma, and others. Today, a few such tests exist for acute myelogenous leukemia (AML). This review evaluates the tests available for assessing minimal residual disease in AML: morphology, growth in vitro, cytogenetics, magnetic resonance imaging, polymerase chain reaction (PCR)-based assays for translocation products, and multiparameter flow cytometry. Of these, multiparameter flow cytometry appears most promising. Studies using multiparameter flow cytometry to identify leukemic cells by aberrant antigen expression have reported a high positive predictive value with regard to the incidence of relapse. In addition, the test is specific, rapid, inexpensive, and applicable to a sufficiently broad group of patients, allowing its use outside of the research laboratory setting. Judicious use of some of the available assays singly or in combination should identify patients harboring residual leukemic cells.
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PMID:Detection of minimal residual disease in acute myelogenous leukemia. 774 61

The status of hemopoietic stem cell transplantation in Australia from January 1, 1993 to December 31, 1993 is reported. A total of 523 hematopoietic stem cell transplants were carried out throughout Australia during this 12 month period: 296 autologous transplants, 223 allogeneic transplants, and 4 syngeneic transplants. These were carried out by transplant programs in 20 hospitals, and the total number of transplants represented a 9.4% increase on the total number performed in 1992 (n = 478). Of the 296 autologous transplants, 133 utilized blood stem cells only, 125 marrow stem cells only, and 38 both. The most common indications for autologous transplant were non-Hodgkin's lymphoma (n = 92), acute myeloid leukemia (n = 53), breast cancer (n = 37), Hodgkin's disease (n = 33), and myeloma (n = 25). The most common indication for allogeneic transplantation was chronic myeloid leukemia (n = 59), acute myeloid leukemia (n = 56), acute lymphoblastic leukemia (n = 43), and severe aplastic anaemia (n = 14). The number of allogenic transplants performed for individual diseases was comparable between 1992 and 1993, but increases in the number of autologous transplants for non-Hodgkin's lymphoma (26%), Hodgkin's disease (45%), breast cancer (48%), and myeloma (20%) were seen.
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PMID:Hematopoietic stem cell transplantation in Australia in 1993. 775

A 95 kDa membrane protein (P-95) has been previously noted to be overexpressed in a doxorubicin-resistant subline of the MCF-7 breast cancer line and in clinical samples obtained from patients with solid tumours refractory to doxorubicin. We performed Western blotting on blast cell lysates from adults with acute myeloid leukaemia, using antisera to P-95. Concomitant flow cytometric assays measured daunorubicin accumulation and retention. Blasts from 16/46 patient samples had detectable P-95 and had reduced accumulation of daunorubicin compared with the negative marrows. Experiments with the P-95 positive MCF-7 multidrug-resistant subline demonstrated decreased daunorubicin accumulation and retention relative to the sensitive parent line. AML blast cells positive for P-95 also demonstrated greater overall in vitro survival in the presence of daunorubicin relative to the P-95-negative samples. The expression of P-95 did not correlate with failure to achieve an initial complete remission with daunorubicin and cytarabine induction chemotherapy. We conclude that the P-95 protein may possess an efflux transporter function, and may represent another mechanism responsible for anthracycline resistance in acute myeloid leukaemia.
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PMID:Expression of a 95 kDa membrane protein is associated with low daunorubicin accumulation in leukaemic blast cells. 781 48


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