Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Seven patients with acute leukemia were treated intravenously with low doses of transferrin-Adriamycin conjugate. The total amount of drug given each patient was far below known toxicity levels for free Adriamycin. The number of tumor cells in peripheral blood diminished in treated patients, and bone marrow aspirates showed no evidence of disease progression. Two patients gave a febrile response and no hypersensitivity reactions were observed. Results of parallel basic research have shown that transferrin receptors on acute leukemia cells bind transferrin-Adriamycin conjugates, and kill by mechanisms at either the plasma membrane or nuclear levels, or both. Such conjugates may provide an alternative to monoclonal antibody drug targeting.
Mol Biother 1990 Mar
PMID:Preliminary clinical study of transferrin-adriamycin conjugate for drug delivery to acute leukemia patients. 233 38

Anthracyclines are an important class of cytotoxic drugs that are frequently used in cancer chemotherapy, especially in acute leukemia. The pharmacokinetics and disposition of these compounds in whole animals and in cells have been studied employing 3H-labeled forms. However, their usefulness is limited by their low specific activities and the low energy of 3H. Therefore, we have labeled daunomycin using 125I-Bolton-Hunter reagent. The resultant anthracycline analogue, iodomycin, has a specific activity of approximately 2000 Ci/mmol. Although this compound was 10-fold less toxic to normal cells than daunomycin, multidrug-resistant cells were cross-resistant to it. Like other drugs to which these cells are cross-resistant, its accumulation by them was greatly reduced, compared with drug-sensitive cells. We have also utilized this compound in photoaffinity labeling experiments to identify its target in multidrug-resistant cells. We observed the specific binding of iodomycin to P-glycoprotein in membrane vesicles as well as in intact cells, thereby directly demonstrating that this protein specifically binds anthracyclines as well as Vinca alkaloids.
Mol Pharmacol 1989 Apr
PMID:Preparation and utility of a radioiodinated analogue of daunomycin in the study of multidrug resistance. 256 17

Leukemic cells from 39 patients with acute leukemia (20 lymphocytic and 19 myelogenous) were examined by transmission electron microscopy and the nucleus and cytoplasm were measured on the micrographs with a computer-controlled image analyzer. The ratios between the areas of the nucleus and whole cell profile (nucleus/cell ratio), heterochromatin and euchromatin, the nucleolus and nucleus, and the degree of irregularity of the nucleus were compared between the two major types of leukemia studied. Acute lymphocytic leukemia (ALL) cells had a relatively larger nucleus and relatively less cytoplasm than acute myelogenous leukemia (AML) cells, and a greater proportion of the area of the nucleus was occupied by heterochromatin in ALL cells than in AML cells. According to the FAB classification, L1 cells are characterized by narrow, and L2 cells by wide cytoplasm based on light microscopic observation of smeared cells, and we confirmed these features by morphometry of May-Giemsa-stained blood smears. However, by electron microscopy there was no difference in the nucleus/cell ratio between L1 and L2 cells, this constituting a discrepancy between the results obtained by electron and light microscopic morphometry. In addition there was no difference in the degree of nuclear irregularity between L1 and L2 cells. Among AML subtypes, significant differences were observed only in the nucleus/cell ratio between M3 and M1, M2 or M4 cells, and in the heterochromatin/euchromatin ratio between M5 and M1, M2 or M3 cells. In conclusion, electron microscopic morphometry revealed marked differences between ALL and AML, but the differences among their subtypes defined by the FAB classification based on nonmorphometric light microscopy were less evident by electron microscopic morphometry.
Virchows Arch B Cell Pathol Incl Mol Pathol 1987
PMID:Morphometrical evaluation of acute leukemic cells by electron microscopy. Discrepancy between morphological characteristics in FAB classification and electron microscopic morphometry. 288 63

A morphometric analysis was performed on trephine biopsies of the bone marrow to identify atypical megakaryocyte proliferation following PAS staining and the immunohistological demonstration of factor VIII. This study includes nine patients with a megakaryoblastic crisis in chronic myeloid leukemia (CML), four with acute megakaryoblastic leukemia (AM) and three with myeloid dysplasia later evolving into overt acute leukemia. Comparison and statistical evaluation of the PAS reaction with anti-factor VIII staining reveals that the latter technique not only facilitates the recognition of immature and abnormal megakaryocytes, but leads to a significantly increased count for all megakaryocytic elements in the bone marrow. Thus our retrospective investigation of routinely processed and paraffin-embedded trephine biopsies shows that the diagnosis of a megakaryoblastic crisis in CML as well as AM may be easily established with the aid of the anti-factor VIII method. In all cases of megakaryoblastic proliferation in CML and AM, the appearance of blasts was associated with moderate to pronounced myelofibrosis which could be also determined by morphometry.
Virchows Arch B Cell Pathol Incl Mol Pathol 1987
PMID:The use of the anti-factor VIII method on trephine biopsies of the bone marrow for the identification of immature and atypical megakaryocytes in myeloproliferative diseases and allied disorders. A morphometric study. 289 11

The transforming sequences of the avian acute leukemia virus, E26, contain two distinct oncogenes, v-mybE and v-ets, fused together. By using a probe containing v-ets sequences, polyadenylated transcripts of the c-ets proto-oncogene were detected in avian tissues; they included a major 7.0-kilobase and a minor 2.0-kilobase species. These c-ets mRNAs were detected at high levels only in lymphoid organs and in avian T and B lymphoid cell lines. A similar pattern of c-ets transcription was observed in human hematopoietic cell lines, with transcripts detected in lymphoid B and T cells but not in erythroid or myeloid cells. The E26 oncogene was inserted into an inducible expression vector, and a 90-kilodalton protein (bp90) was produced in bacteria. Rabbit antisera raised to purified bp90 precipitated P135gag-mybE-ets, the v-mybE-ets polyprotein expressed in E26-transformed cells, and also reacted with p50v-mybA, the transforming protein of the avian myeloblastosis virus. Antiserum to bp90 was absorbed with a bacterially synthesized v-mybA protein to remove anti-myb activity. The absorbed anti-bp90 serum retained the ability to immunoprecipitate P135gag-mybE-ets from E26-transformed cells and specifically reacted with a 56-kilodalton polypeptide (p56) detected in chicken lymphoid organs and in T and B lymphocytes of both avian and human origin. The data suggest that p56 is a translational product of the c-ets proto-oncogene and imply that p56 may be involved in regulating the growth of lymphoid cells.
Mol Cell Biol 1985 Nov
PMID:The proto-oncogene c-ets is preferentially expressed in lymphoid cells. 301 92

An infant case of acute leukemia (AL) showed lineage infidelity and a chromosome rearrangement involving 11q23. This case was morphologically diagnosed as ALL-L2 according to the FAB classification. However, the blast cells were highly positive for monoclonal antimyeloid antigens (Mol and TG-8) and lymphoid markers (B1, J5 and TdT). These immunologic findings indicated that the blast cells had characteristics of lymphoid B-cell and myeloid lines. In the literature, so-called "11q23 chromosome abnormalities," commonly observed in acute nonlymphoblastic leukemia (ANLL) and in a subtype of acute lymphoblastic leukemia (ALL) with t(4;11) were observed in both lymphoid and myeloid acute leukemias, with some of them recently reported to have lineage infidelity. These unique characteristics may indicate the possibility that the latter is a variation of the former, and support the hypothesis that the chromosomal rearrangement at 11q23 occurs at a multipotent stem-cell level.
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PMID:Infantile acute leukemia with 11q23 chromosome abnormality and lineage infidelity. 316

The distribution of Alu-family DNA repeats (AFRs) in chromosomes of phytohaemagglutinin-stimulated peripheral blood lymphocytes of four normal donors and non-stimulated bone marrow cells of four patients with acute leukemia (ALL and ANLL) was studied by in situ hybridization using DNA of recombinant phage lambda containing multiple inserts of AFR as a probe. Over some chromosome bands (14cen, 16p13, 16cen) from normal donors and from leukemic patients clusters of silver grains were detected. Over other three bands (3q26, 8p11-p12 and 14q24) the clusters were found only in chromosomes from the four acute leukemia patients, and were absent from chromosomes of healthy donors. The results suggest non-random long-range distribution of AFRs in human chromosomes, and somatic variations in the distribution of the repeats.
Mol Biol Rep 1988
PMID:'Conservative' and 'variable' clusters of Alu-family DNA repeats in human chromosomes. 322 44

The dispersion of the Alu-family DNA repeats in phytohemagglutinin-stimulated lymphocytes from peripheral blood of normal donors as well as in nonstimulated bone marrow cells of four patients suffering from acute leukemia was studied by hybridization on metaphase chromosomes in situ. DNA of bacteriophage lambda CAR42 clone containing the insertion of at least 8 copies of Alu-family DNA-repeats and labelled with tritium was used as a probe in hybridization. All patients with acute leukemia had the same pattern of changes in hybridization of the bone marrow cells. It consists of silver grains clustering over 3q26, 8p12, 14q24. The pattern may reflect amplification transposition of Alu-family DNA repeats in the human genome connected with cellular differentiation or malignant transformation of blood cells.
Mol Gen Mikrobiol Virusol 1988 Nov
PMID:[Differences in the localization of Alu-repeats in various chromosomes of peripheral blood cells from normal donors and bone marrow cells from patients with acute leukemia]. 323 36

Cells from 95 patients with acute leukemia were studied by cytochemistry, light microscopy, and transmission electron microscopy (TEM), and were classified according to the French-American-British (FAB) guidelines. This group included 63 patients with acute nonlymphocytic leukemia (ANLL) de novo, 18 with acute lymphocytic leukemia (ALL), and 14 with ANLL as a second malignancy. In addition, 13 cases of chronic myelocytic leukemia in blast crisis were studied. Ultrastructural examination resulted in reclassification of 6 cases of ANLL de novo; two of these were reclassified from M2 (myeloblastic leukemia with maturation) to M3 variant (microgranular variant of hypergranular promyelocytic leukemia). The classification of the cases of CML in blast crisis was identical by light microscopy and TEM. IN 1 case of myeloblastic crisis, however, basophilic granules were demonstrated by TEM but were not appreciated by light microscopy. Classification of the cases of secondary leukemia was possible by light microscopy and cytochemistry in all 14 cases, but was often difficult since the cytochemical reactions were usually less intense than in de novo ANLL. This was particularly true in those cases classified as M1, and in such cases, TEM was required to confirm the diagnosis.
Virchows Arch B Cell Pathol Incl Mol Pathol 1982
PMID:Ultrastructural characterization of de novo and secondary leukemias. 612 30

Acute leukemias containing > 3% myeloperoxidase (MPO)-positive blast cells, as detected cytochemically, are considered to be myelogenous in origin, regardless of the immunophenotypic markers expressed. Conversely, acute leukemias that express only myeloid antigens are also considered to be acute myelogenous leukemia (AML), even in the absence of MPO. These MPO-negative AMLs, designated AML-M0 in the FAB classification, currently require either immunophenotypic or electron microscopic studies for identification. To examine the association of MPO and myeloid antigen expression in AML, particularly at the early stages of myeloid cell differentiation, we have used in situ hybridization (ISH) to evaluate MPO gene expression in myeloid leukemia cell lines and a variety of well-characterized acute leukemias, including six cases of AML-M0. Strong positivity for MPO mRNA was detected in the myeloid leukemia cell line HL-60 and in 22 of 27 AMLs (three AML-M0, four AML-M1, eight AML-M2, five AML-M4, two AML-M5a). No MPO gene expression was detected in three AML-M0, one AML-M5a, one AML-M7, 5 acute lymphoblastic leukemia, the lymphoid cell lines Molt-4 and Namalwa, or in the early myeloid cell lines KG-1 and KG-1a. Ultrastructural studies for MPO activity were performed on four AML-M0; one leukemia showed both gene expression and cytochemical activity, whereas two others contained neither MPO transcripts nor enzyme. Weak MPO gene expression was evident in one AML-M0 that was negative for enzymatic activity by electron microscopy. These studies show MPO gene expression can be detected by ISH in about half of AML-M0, supporting their presumed myelocytic derivation.(ABSTRACT TRUNCATED AT 250 WORDS)
Diagn Mol Pathol 1995 Sep
PMID:Detection of myeloperoxidase gene expression in minimally differentiated acute myelogenous leukemia (AML-M0) using in situ hybridization. 749 41


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