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)

Leukemic blast growth factors (LBGFs) are necessary for in vitro growth of clonogenic cells from patients with acute myeloblastic leukemia. As the human bladder carcinoma cell line 5637 had previously been reported to secrete abundant LBGFs into the culture supernatant, the LBGFs in 5637-conditioned medium (5637-CM) were characterized. Measurement of LBGFs was done using an in vitro leukemic blast colony assay in methylcellulose culture. LBGFs in 5637-CM were fractionated by anion exchange chromatography, and two peaks of activity were recovered. Pool B (high-salt eluent) and/or purified granulocyte colony-stimulating factor (G-CSF) were added to the clonogenic leukemic blast cell assays. It was found that pool B was more active than G-CSF in the majority of cases examined and that the two types of activity were synergistic in some cases.
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PMID:Synergism of leukemic blast growth factors in medium conditioned by human bladder carcinoma cell line 5637. 348 Sep 13

An immunoconjugate was prepared containing a disulfide linker between a murine monoclonal antibody (5E9), which recognized the human transferrin receptor, and the ribosome-inactivating protein gelonin. This immunoconjugate was found to consist of two major species, 5E9-gelonin2 and 5E9-gelonin1, and a minor species of 5E9-gelonin3 and less than 10% of either free antibody or gelonin. 5E9-gelonin was extremely toxic in vitro to human tumor cell lines expressing the 5E9 antigen, including a Burkitt's lymphoma, an adult T-cell acute lymphocytic leukemia, an acute myelogenous leukemia, a promyelocytic leukemia, and a cervical carcinoma line. A 24-hour exposure to 10(-9) M immunoconjugate killed 90-99.9% of tumor cells, depending on the cell line. A 5E9-negative murine leukemia was not sensitive to this conjugate. Pharmacokinetic analysis of the disappearance of this immunoconjugate from the murine circulation revealed that it had a biphasic clearance, with an initial rapid phase with a half-life (t1/2) of 3 hours and a later, slower phase with a t1/2 of about 1 day. Analysis of blood samples by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis revealed that a substantial degree of disulfide-linker breakdown occurred in vivo and that the 5E9-gelonin2 species was cleared more rapidly than the 5E9-gelonin1. With use of the same clonogenic assays used to measure in vitro toxicity, biologically active immunoconjugate could be detected in murine plasma for up to 24 hours after iv administration, but the concentration of immunoconjugate by this measure was considerably less than that predicted by SDS-gel electrophoresis. The ability to deliver immunoconjugate to tumor cells in vivo was studied with use of the Burkitt's lymphoma Namalwa as a xenograft in nude mice. It was possible to deliver substantial amounts of immunoconjugate to Namalwa cells in xenografted ascites with direct ip inoculation; lower but significant amounts of immunoconjugate could be delivered to this xenograft after systemic iv administration, provided the tumor burden was low. The 5E9-gelonin conjugate, when administered iv at the time of ip tumor inoculation, prolonged survival of nude mice bearing Namalwa or other human tumors as ascites xenografts and delayed or prevented the growth of subcutaneous nodules of Namalwa in an antigen-specific fashion after a single iv injection. Direct intratumoral administration also inhibited the growth of visible subcutaneous nodules of Namalwa. This immunoconjugate may be useful in the treatment of human cancer.
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PMID:An immunotoxin composed of a monoclonal antitransferrin receptor antibody linked by a disulfide bond to the ribosome-inactivating protein gelonin: potent in vitro and in vivo effects against human tumors. 350 Mar 56

Autologous bone marrow transplantation (ABMT) is a new technique which is currently being evaluated in the treatment of leukemias, lymphomas, and a few solid tumors. In patients with acute leukemia (AL), high dose therapy + ABMT is of little benefit if done at time of relapse. On the other hand, when used for consolidation of remission, either with cleansed or non cleansed marrow, it may improve disease-free survival. In patients with acute myelocytic leukemia (AML) autografted during their 1st remission, the probability of remaining in remission at 2 years is 70 p. 100. It is slightly lower for patients with acute lymphocytic leukemia (ALL): 55 p. 100. The different techniques of cleansing the marrow, monoclonal antibodies, immunotoxins, drugs, are reviewed in this paper. A comparison of these techniques in term of tumor log cell kill is provided. ABMT is the best second line therapy for non-Hodgkin lymphomas (NHL), either after relapse after conventional chemotherapy or partial failure (partial remission). In these patients, the probability of remaining in remission at 3 years is about 50 p. 100. ABMT is currently under trial in the treatment of solid tumors and some success has been obtained in carcinoma of the ovary, non-seminomatous tumor of the testis, neuroblastoma, and some selected breast cancers.
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PMID:[Autograft of bone marrow for the treatment of acute leukemia: in vitro efficacy of anti-leukemic purification]. 352 33

From June 1973 to May 1978, a total of 845 women with resectable breast cancer and positive axillary nodes were entered into two consecutive randomized studies evaluating adjuvant chemotherapy. All patients were subjected to radical or modified radical mastectomy, none received postoperative radiation, and 666 were administered adjuvant CMF (cyclophosphamide, methotrexate, and fluorouracil). After a median follow-up in excess of 10 years, no cases of acute nonlymphocytic leukemia were detected, but 21 second solid tumors other than contralateral breast carcinoma were documented. The cumulative frequency was 4% +/- 1.9% after surgery alone, and 4.2% +/- 1.03% following adjuvant CMF. No differences were observed between patients aged up to 50 years (surgery, 3.1% +/- 2.2%; CMF, 3.3% +/- 1.3%) or older than 50 years (surgery, 4.5% +/- 2.6%; CMF, 5.2% +/- 1.8%). During the same period, a total of 29 contralateral breast carcinomas were documented for a cumulative frequency of 3.7% +/- 1.7% after surgery alone and of 5.2% +/- 1.4% following adjuvant CMF, respectively. We conclude that, at present, there is no evidence for an increased risk of second malignancies following adjuvant CMF as given in this series. Our findings would suggest that second tumors documented so far cannot be entirely ascribed to treatment with adjuvant chemotherapy, but they could be due to a chance association.
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PMID:Second malignancies after CMF for resectable breast cancer. 362 43

An avascular, contrast enhancing intraosseous petrous apex mass was discovered on CT in a patient with prior colonic carcinoma and acute myelocytic leukemia. A normal bone scan made metastasis unlikely and surgery revealed a neuroma. The differential diagnosis is discussed.
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PMID:Intraosseous petrous apex neuroma: CT findings. 378 42

A retrospective series of patients with the primary myelodysplastic syndrome has been reviewed and the survival updated. A scoring system is proposed that has advantages in predicting survival outcome. The importance of either dysmegakaryocytopoiesis or dysgranulocytopoiesis is emphasized because of its prognostic impact on leukaemic progression. Over 50 per cent of the patients die from either acute leukaemia or consequences of defective marrow production of granulocytes and platelets. Although only a few cases were included, the RAEB-T group has a very poor outcome and appears much closer to FAB M2 in biologic behaviour than RAEB. Both the criteria for the FAB subtypes and the scoring system can be applied easily in each case of myelodysplasia. Of the 56 patients only 9 were still alive as of April, 1984. Eight of these were in the RA-S and RA categories (or using the scoring system grouping 7 were group 1). All of the 16 patients who progressed to overt AML died within 4 weeks, and none was treated with chemotherapy. Of the remaining 31 patients, half died as a result of infection and/or haemorrhage and the remainder from apparently unrelated causes (cardiovascular, carcinoma, renal failure). These latter deaths are not surprising in light of the median age of 72 years.
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PMID:Modifications in the classification of primary myelodysplastic syndromes: the addition of a scoring system. 385 11

This study consists of 65 patients (pts) who developed a myelodysplastic syndrome (MDS) (39 pts) or acute myeloid leukemia (AML) (26 pts) following chemotherapy and/or radiotherapy; the interval from the onset of therapy to bone marrow abnormality ranged from 11 to 192 months (median, 58). Thirty-three patients had been previously treated for lymphoproliferative diseases, 29 for carcinoma, and three for a nonneoplastic disorder. Approximately 30% of the cases presenting in the MDS phase evolved to AML in one to 12 months (median, 3.5). The AML in 49% of the cases was not readily classified according to French-American-British (FAB) criteria; the primary difficulty in classification related to the involvement of multiple cell lines. Among the cases that could be classified, all FAB types were represented except for M1; M2 was the most frequent type. Clonal chromosome abnormalities were found in marrow specimens from 22 of 24 (92%) patients studied with G banding; 11 had abnormalities of chromosomes 5 and/or 7. The median survival for all patients was four months with no significant difference between those treated and not treated with antileukemic therapy. The median survival was three months for the patients presenting with AML, six months for the patients with AML following an MDS, and four months for the patients with an MDS that did not evolve to AML. The findings in the present study suggest that there are three stages of therapy-related panmyelosis: (1) pancytopenia with associated myelodysplastic changes, (2) a frank MDS, and (3) overt AML. Many patients will present in the stage of overt AML that differs from de novo AML primarily by the high incidence of trilineage involvement, difficulty in classification, frequent cytogenetic abnormalities, and poor response to antileukemic therapy. The myelodysplastic phase, with or without evolution to acute leukemia, is a highly lethal disease with a median survival comparable to that of the patients who present with AML.
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PMID:Therapy-related acute myeloid leukemia and myelodysplastic syndrome: a clinical and morphologic study of 65 cases. 385 44

Two patients with acute myeloblastic leukemia (AML) with double minute chromosomes (dmins) are described. One patient had dmins in approximately one-third of bone marrow cells examined at diagnosis; no other karyotypic changes were observed. The dmins disappeared when the patient achieved a complete remission. The second patient developed acute leukemia as a second cancer, having previously received radiotherapy and chemotherapy for a breast carcinoma. At the time of diagnosis of AML, the patient exhibited dmins in 12% of bone marrow cells; other complex karyotypic changes were observed. Data on the clinical and cytogenetic features of these cases are compared with those of other reported cases of acute leukemia with dmins. The possible biologic and clinical significance of dmins in acute leukemia is discussed.
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PMID:Double minute chromosomes in acute myeloblastic leukemia. 385 71

Circulating blast cells from the peripheral blood of acute myeloblastic leukemia patients include a subpopulation capable of colony formation in the presence of phytohemagglutinin-stimulated leukocyte-conditioned medium (PHA-LCM). We describe the complete replacement in the blast assay of PHA-LCM by conditioned medium from a human bladder carcinoma cell line, HTB9. Both conditioned media contain a stimulator of blast cell growth that elutes as a single peak from a Sephadex G100 column with an apparent molecular weight of 30,000. It is shown that this leukemic blast growth factor is distinct from erythroid-potentiating activity (EPA) and possibly granulocyte macrophage colony-stimulating factor.
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PMID:Production of leukemic blast growth factor by a human bladder carcinoma cell line. 386 Dec 4

The blast cells of acute myeloblastic leukemia (AML) may be considered as a renewal population, maintained by blast stem cells capable of both self-renewal and the generation of progeny with reduced or absent proliferative potential. Blast progenitor renewal is manifested in suspension culture by an exponential increase in clonogenic cells. This growth requires that two conditions be met: first, the cultures must contain growth factors in media conditioned either by phytohemagglutinin (PHA)-stimulated mononuclear leukocytes (PHA-LCM), or by cells of the continuous bladder carcinoma line HTB9 (HTB9-CM). Second, the cell density must be maintained at 10(6) blasts/ml; this may be achieved by adding irradiated cells to smaller numbers of intact blasts. We are concerned with the mechanism of the feeding function. We present evidence that (a) cell-cell contact is required. (b) Blasts are heterogeneous in respect to their capacity to support growth. (c) Fractions containing membranes from blast cells will substitute for intact cells in promoting the generation of new blast progenitors in culture. (d) This membrane function may be specific for AML blasts, since membranes from blasts of lymphoblastic leukemia or normal marrow cells were inactive.
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PMID:Membranes replace irradiated blast cells as growth requirement for leukemic blast progenitors in suspension culture. 386 78


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