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

It has been well established that specific alterations in members of the ras gene family, H-ras, K-ras and N-ras, can convert them into active oncogenes. These alterations are either point mutations occurring in either codon 12, 13 or 61 or, alternatively, a 5- to 50-fold amplification of the wild-type gene. Activated ras oncogenes have been found in a significant proportion of all tumors but the incidence varies considerably with the tumor type: it is relatively frequent (20-40%) in colorectal cancer and acute myeloid leukemia, but absent or present only rarely in, for example, breast tumors and stomach cancer. No correlation has been found, yet, between the presence of absence of an activated ras gene and the clinical or biological features of the malignancy. The activation of ras oncogenes is only one step in the multistep process of tumor formation. The presence of mutated ras genes in benign polyps of the colon indicates that activation can be an early event, possibly even the initiating event. However, it can also occur later in the course of carcinogenesis to initiate for instance the transition of a benign polyp of the colon into a malignant carcinoma or to convert a primary melanoma into a metastatic tumor. Apparently, the activation of ras genes is not an obligatory event but when it occurs it can contribute to both early and advanced stages of human carcinogenesis.
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PMID:The ras gene family and human carcinogenesis. 328 42

Recent research has suggested that nonionizing radiation in the form of power-frequency magnetic fields may play some role in carcinogenesis in general and in acute nonlymphocytic leukemia in particular. Much of the epidemiologic evidence is preliminary in nature and the methods of previous studies have been criticized. In order to further evaluate this hypothesis, a population-based case-control study of adult acute nonlymphocytic leukemia and residential exposure to power-frequency magnetic fields was carried out in western Washington state. Analyses were based on 114 cases who were newly diagnosed from 1981 to 1984 and identified from a population-based cancer registry, and 133 controls who were chosen from the study area by random digit dialing. Magnetic field exposure was estimated from external electrical wiring configurations within 140 ft (42.7 m) of each subject's residence. In addition, magnetic fields were measured inside the subject's residence at the time of interview. Neither the directly measured magnetic fields nor the surrogate values based on the wiring configurations were associated with acute nonlymphocytic leukemia.
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PMID:Acute nonlymphocytic leukemia and residential exposure to power frequency magnetic fields. 338 18

Acute myeloid leukemia or one of its variants is being reported with increasing frequency as a second neoplasm in patients being treated for multiple myeloma, Hodgkin's disease, non-Hodgkin's lymphoma and a variety of other primary neoplasms and non-neoplastic diseases. Although many of these patients were treated with both chemotherapy and radiotherapy, many received no radiotherapy at all. Drugs most frequently implicated in the causation of acute leukemia and other second neoplasms are the alkylating agents, procarbazine and the nitrosoureas. The frequency of this syndrome varies from less than 1 per cent to 7 per cent in many reported series of patients. There could develop a reluctance to use cytotoxic agents to treat malignant neoplasms for fear of inducing acute leukemia. Although one has to consider this complication, one should not, however, withhold these drugs from a patient with a neoplasm or other potentially fatal disease in whom such therapy is the treatment of choice. We seem to be faced with the paradox that patients benefiting most from chemotherapy may be at highest risk of suffering its undesirable consequences. Although the risk of leukemogenesis or carcinogenesis in man may be small, these drugs should be used with caution in patients with indolent non-neoplastic diseases such as rheumatoid arthritis.
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PMID:Cancer and secondary leukemia. 657 7

A child diagnosed with Stage IVB Hodgkin disease at nine and one-half years of age subsequently developed osteosarcoma and acute myelogenous leukemia ten years after her initial diagnosis. She received multiple courses of radiotherapy and several single chemotherapeutic agents for her Hodgkin disease. Theraphy-induced multiple malignancies and intrinsic predisposition to carcinogenesis in this case is discussed.
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PMID:Osteosarcoma and acute myeloblastic leukemia after therapy for childhood Hodgkin disease - a case report. 693 64

The authors describe a combination technique enabling detection of in situ hybridization (ISH) signals from chromosome-specific probes in interphase or mitotic cells that still retain the alkaline phosphatase antialkaline phosphatase (APAAP) or Sudan black B (SBB) staining reactions (simultaneous detection) or have been first classified morphologically and then by APAAP or SBB. The technique can be used on cell suspensions, in situ cultures and tissue sections. Examples from leukemias (chronic lymphocytic, myeloid, and acute myeloid leukemia) and solid tumors (chondromyxoid fibroma and glioblastoma) illustrate the potential of the technique in investigation of cancer tissue heterogeneity. In leukemias, it can be used to study cell lineage involvement, stem cells, and minimal residual disease, as well as to monitor therapy. In solid tumors, it can be used to identify neoplastic areas of tissue and to track the site of origin of neoplastic cells. Finally, it can be used to study the significance of chromosome abnormalities in carcinogenesis.
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PMID:Analysis of phenotype and genotype of individual cells in neoplasms. 768 32

Several phase II clinical studies of all-trans-retinoic acid (ATRA) have been conducted in acute promyelocytic leukemia (APL), an uncommon subtype of acute myeloid leukemia (AML). ATRA has been shown to induce complete remission (CR) in 64% to 96% of patients with APL, and with rapid resolution of the coagulopathy, which is a major cause of early morbidity and mortality. Although CRs induced with ATRA alone are usually not sustained and intensive antileukemic consolidation therapy is required to prolong remission, these findings indicate that a new approach of differentiation therapy is effective in treating patients with APL and may potentially be effective in other malignancies. The presence of the PML/retinoic acid receptor-alpha (PML/RAR-alpha) fusion gene, produced as a result of the unique chromosomal translocation in APL, is a marker of sensitivity to ATRA. Aside from the complications of hyperleukocytosis and the retinoic acid syndrome, ATRA therapy is generally well tolerated. An international study (Intergroup 0129), headed by the Eastern Cooperative Oncology Group, is currently under way to determine further the role of ATRA in the treatment of patients with APL. Given its success in APL, studies of ATRA in other hematologic malignancies are also being conducted. A better understanding of how retinoids modulate carcinogenesis will help determine if the results in APL can be realized in other malignancies treated with ATRA or other retinoids.
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PMID:All-trans-retinoic acid in acute promyelocytic leukemia and its potential in other hematologic malignancies. 783 84

The WT1 gene encoding a zinc finger polypeptide is a tumor suppressor gene that plays a key role in the carcinogenesis of Wilms' tumor. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to examine relative levels of WT1 gene expression (defined in K562 cells as 1.00) in 45 patients with acute myelogenous leukemia (AML), 22 with acute lymphocytic leukemia (ALL), 6 with acute mixed lineage leukemia (AMLL), 23 with chronic myelogenous leukemia (CML), and 24 with non-Hodgkin's lymphoma. Significant levels of WT1 gene were expressed in all leukemia patients and for CML the levels increased as the clinical phase progressed. In striking contrast with acute leukemia, the levels of WT1 gene expression for NHL were significantly lower or even undetectable. Clear correlation was observed between the relative levels of WT1 gene expression (< 0.6 v > or = 0.6) and the prognosis for acute leukemia (AML, ALL, and AMLL). Patients with less than 0.6 levels had significantly higher rates of complete remission (CR), disease-free survival, and overall survival than those with > or = 0.6 levels, whereas CR could not be induced in any of the 7 patients with acute leukemia having greater than 1.0 levels of WT1 gene expression. The quantitation of the WT1 gene expression made it possible to detect minimal residual disease (MRD) in acute leukemia regardless of the presence or absence of tumor-specific DNA markers. Continuous monitoring of the WT1 mRNA was performed for 9 patients with acute leukemia. In 4 patients, MRD was detected 2 to 8 months before clinical relapse became apparent. In 2 other patients, the WT1 mRNA gradually increased after discontinuation of chemotherapy. No MRD was detected in the remaining 3 patients with AML who received intensive induction and consolidation therapy. Simultaneous monitoring of MRD by RT-PCR using primers for specific DNA markers in 3 patients (2 AML-M3 with PML/RAR alpha, and 1 AML-M2 with AML1/ETO) among these 9 patients detected MRD comparable with that obtained from quantitation of WT1 gene expression. In a patient with acute promyelocytic leukemia, the limits of leukemic cell detection by RT-PCR using either WT1 or promyelocytic leukemia/retinoic acid receptor-alpha gene primers were 10(-3) to 10(-4) and 10(-4) for bone marrow, and 10(-5) and 10(-4) for peripheral blood, respectively. Therefore, we conclude that WT1 is a new prognostic factor and a new marker for the detection of MRD in acute leukemia.
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PMID:WT1 as a new prognostic factor and a new marker for the detection of minimal residual disease in acute leukemia. 794 79

We have used the vitamin D analogue, 1 alpha,25-dihydroxy-16-ene-23-yne-26,27-hexafluorocholecalcifero l (Ro24-5531), for inhibition of mammary carcinogenesis induced by N-nitroso-N-methylurea (NMU) in Sprague-Dawley rats. Rats were first treated with a single dose of either 15 or 50 mg/kg body weight NMU and then fed Ro24-5531 (2.5 or 1.25 nmol/kg of diet) for 5-7 months. Ro24-5531 significantly extended tumor latency and lessened tumor incidence as well as tumor number in rats treated with the lower dose of NMU. In rats treated with the higher dose of NMU, Ro24-5531 was fed in combination with tamoxifen; in these experiments, Ro24-5531 significantly enhanced the ability of tamoxifen to reduce total tumor burden, as well as to increase the probability that an animal would be tumor free at the end of the experiment. In vitro, Ro24-5531 was 10-100 times more potent than 1,25-dihydroxyvitamin D3 for inhibition of proliferation of human breast cancer cell lines as well as primary cultures of cells from 2 patients with acute myelogenous leukemia. When fed chronically, Ro24-5531 did not elevate serum calcium in the present studies. We propose the new term, "deltanoids," for the set of molecules composed of vitamin D and its synthetic analogues, in a manner similar to the naming of "retinoids" for the corresponding set of molecules related to vitamin A.
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PMID:1 alpha,25-Dihydroxy-16-ene-23-yne-26,27-hexafluorocholecalciferol (Ro24-5531), a new deltanoid (vitamin D analogue) for prevention of breast cancer in the rat. 813 76

Fc gamma RIII is a low affinity immunoglobulin G receptor expressed by neutrophils, natural killer cells, and macrophages. Soluble forms of Fc gamma RIII have been identified in serum, plasma, and other body fluids. Previous studies showed that Fc gamma RIII appeared late in myeloid differentiation. This retrospective study was designed to measure the concentration of soluble Fc gamma RIII in serum from patients with acute myelogenous leukemia (AML), a disease generally characterized by granulocytopenia and an increase in circulating myeloblasts and occasionally promyelocytes. Frozen serum samples from patients with AML and from age-matched normal donors were obtained from the Biological Carcinogenesis Branch Repository of the National Cancer Institute. We used an ELISA to measure the concentration of soluble Fc gamma RIII in these serum samples and observed significantly lower concentrations of soluble Fc gamma RIII in the serum of AML patients. The mean concentration of soluble Fc gamma RIII was 9.5 nM in normals (n = 48) and 5.4 nM in AML patients (n = 46), (p < 0.0005). Whether this difference is due to defects in granulopoiesis in these patients or to other parameters of the disease is unknown at this time. Our retrospective study should provide the basis for subsequent investigation of patients with AML to correlate soluble Fc gamma RIII concentrations with the clinical status of the patients.
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PMID:Soluble Fc gamma RIII is present in lower concentrations in the serum of patients with acute myelogenous leukemia (AML): a retrospective study. 835 Jun 25

Chromosome 2 abnormalities, particularly interstitial deletions, characterize murine radiation-induced acute myeloid leukaemias (AMLs). Here, G-band analyses in CBA/H mice of early (1-6 month) post 3 Gy X-irradiation events in bone marrow cells in vivo and of karyotype evolution in one unusual AML are presented. The early event analysis showed that all irradiated animals carry chromosome 2 abnormalities, that chromosome 2 abnormalities are more frequent than expected and that interstitial deletions are more common in chromosome 2 than in the remainder of the genome. On presentation AML case N122 carried a t(2;11) terminal translocation which, with passaging, evolved into a del2(C3F3). Therefore, two pathways in leukaemogenesis might exist, one deletion-driven, the other terminal translocation-driven involving interstitial genes and terminal genes respectively of chromosome 2. As all irradiated individuals carried chromosome 2 abnormalities, the formation of these aberrations does not determine individual leukaemogenic sensitivity as only 20-25% of animals would be expected to develop AML. Similar lines of argument suggest that chromosome 2 abnormalities are necessary but not sufficient for radiation leukaemogenesis in CBA/H nor are they rate limiting in leukaemogenesis.
Carcinogenesis 1996 Apr
PMID:Chromosomal mechanisms in murine radiation acute myeloid leukaemogenesis. 862 74


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