Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors describe a coherent model for differentiated leukemias derived from physiopathological studies on Friend leukemia. In Friend leukemia, Friend virus induces permanent differentiation of erythropoietin-responsive cells. This erythropoietic proliferation and maturation is accompanied by a marked cell loss and provokes enlargement of the stem cell compartment. The so-called leukemic cells have a limited proliferation capacity and may not be truly malignant as opposed to blastic cells in acute leukemias. Clinical, hematological, and physiopathological data that are presently available in chronic granulocytic leukemia, polycythemia vera, and the erythroblastic component of erythroleukemia are compatible with the Friend physiopathological model. It is suggested that these differentiated leukemias initiate from an uncontrolled differentiation of a committed cell compartment, which stimulates proliferation of the stem cell compartment. The disease would be due to a proliferation and accumulation of "subnormal" cells characterized by a shorter mean life-span than the normal differentiated cell population. Although limited, the data available suggest that the physiopathology of acute leukemias is clearly distinguishable from that of differentiated leukemias; several immunological and therapeutic applications of this model are outlined.
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PMID:Physiopathology of human and virus-induced murine leukemias. 17 21

Erythroblastic transformation of chronic granulocytic leukemia was found in seven of 67 unselected patients with blast crisis. This morphologic picture of erythroblastic transformation was indistinguishable from that in erythroleukemia or Di Guglielmo's syndrome. The median survival of the patients with erythroblastic transformation was two months, considerably less than the four-month median survival in the entire series of 67 patients. Only two brief partial remissions were obtained with combination chemotherapy. The causes of death were primarily hemorrhage and infection, related to thrombocytopenia and neutropenia. In this regard, the patients with erythroblastic transformation resembled all the patients with blast crisis and patients with acute leukemia in general. The erythroblastic transformation seems to represent a morphologic variant of chronic granulocytic leukemia blast crisis, without apparent prognostic or therapeutic implications.
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PMID:Erythroblastic transformation of chronic granulocytic leukemia. 26 30

The following rare Ph1-positive chromosome constitutions, based on the cytogenetic findings in three cases with acute leukemia, are presented. 1) A hypodiploid karyotype, primarily 43, -X, -7, -8,9p+ and a Ph1, in a patient with acute lymphoblastic leukemia (ALL) in relapse, followed by a complete remission and a normal chromosomal picture and then by the appearance of cells with a 46,XX,Ph1 karyotype. The Ph1 was due to a standard translocation between chromosomes no. 9 and no. 22. 2) The first demonstration of an unusual Ph1-translocation between chromosomes no. 19 and no. 22 in a condition other than chronic myelocytic leukemia (CML), i.e., acute myeloblastic leukemia (AML). 3) The presence of a Ph1 in acute erythroleukemia (EL) due to a translocation between chromosomes no. 4 and no. 22, this apparently being the first description of such a translocation in any disease. The cytogenetic findings, particularly those in the Ph1-positive case of ALL, were evaluated in relation to the cytologic and immunologic features, clinical courses and implications, and the interrelationship between the three conditions (AML, blastic phase of CML and ALL), which have to be considered in cases of Ph1-positive acute leukemia.
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PMID:Chromosomes and causation of human cancer and leukemia. XXV. Significance of the Ph1 (including unusual translocations) in various acute leukemias. 33 21

The distribution of various types of leukemia due to chronic exposure to benzene is described in a series comprising 34 cases. The incidence of leukemia among 31 show-workers was 13.5/100,000. Acute myeloblastic leukemia was the most frequent type, followed by preleukemia, acute erythroleukemia and acute lymphoblastic leukemia. The extreme rarity of chronic myeloid leukemia was a noteworthy finding. The differences and similarities between the distribution of various types of leukemia in different series of patients with chronic exposure to benzene and ionizing radiation are discussed.
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PMID:Types of leukemia in chronic benzene poisoning. A study in thirty-four patients. 81 44

Patients with myeloproliferative disorders were prospectively studied by in vitro agar-gel marrow culture technics to evaluate factors involved in the evolution of abnormal granulopoiesis. Marrow granulocytic colony-forming capacity was determined in 78 patients with chronic myeloid leukemia, subacute myeloid leukemia, preleukemia, Di Guglielmo's syndrome, polycythemia vera or essential thrombocythemia. A wide range of marrow colony-forming capacity values was noted early in disease courses; however, in 26 of 33 patients decreased colony-forming capacity was associated with disease transformation into acute myeloid leukemia or other clinically aggressive stages. An increased proportion of abnormally light buoyant density (less than 1.062 g/cm3) colony-forming cells was present in the marrow and peripheral blood of 15 of 16 patients with chronic myeloid leukemia, subacute myeloid leukemia, preleukemia or essential thrombocythemia; in seven of eight patients with greater than 35 per cent abnormally light colony-forming cells their disease subsequently underwent transformation. Elevated levels of urinary colony-stimulating factor output were noted in 17 of 31 patients, and in 10 of 12 patients whose disease subsequently underwent acute transformation within 10 months of study. In six of seven patients who simultaneously had an increased urinary output of colony-stimulating factor and low colony-forming capacity in marrow, transformation occurred within 10 months. These findings indicate that progressive abnormalities of both marrow clonal growth patterns and levels of possible humoral regulatory substances develop during evolution of these diseases. In contrast, patients with idiopathic sideroblastic ineffective erythropoiesis had normal values for marrow colony-forming capacity, proportion of light density colony-forming cells and urinary colony-stimulating factor output, and in none has their disease transformed into acute myeloid leukemia. These in vitro studies appear useful for clinical staging, evaluating prognosis and categorizing patients with myeloproliferative disorders.
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PMID:The myeloproliferative disorders. Correlation between clinical evolution and alterations of granulopoiesis. 108 34

The SCL (tal-1, TCL5) gene is a member of the basic domain, helix-loop-helix (bHLH) class of putative transcription factors. We found that (i) the SCL promoter for exon Ia contains a potential recognition site for GATA-binding transcription factors, (ii) SCL mRNA is expressed in all erythroid tissues and cell lines examined, and (iii) SCL mRNA increases upon induced differentiation of murine erythroleukemia (MEL) cells, and inferred that SCL may play a physiologic role in erythroid differentiation. We used gel shift and transfection assays to demonstrate that the GATA motif in the SCL promoter binds GATA-1 (and GATA-2), and also mediates transcriptional transactivation. To identify a role for SCL in erythroid differentiation, we generated stable transfectants of MEL and K562 (a human chronic myelogenous leukemia cell line that can differentiate along the erythroid pathway) cells overexpressing wild-type, antisense or mutant SCL cDNA. Increasing the level of SCL expression in two independent MEL lines (F4-6 and C19, a 745 derivative) and K562 cells increased the rate of spontaneous (i.e. in the absence of inducer) erythroid differentiation. Conversely, induced differentiation was inhibited in MEL transfectants expressing either antisense SCL cDNA or a mutant SCL lacking the basic domain. Our experiments suggest that the SCL gene can be a target for the erythroid transcription factor GATA-1 and that the SCL gene product serves as a positive regulator of erythroid differentiation.
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PMID:The SCL gene product: a positive regulator of erythroid differentiation. 139 92

Nine patients with chronic myelocytic leukemia (CML) and 1 patient with erythroleukemia were studied with 3'bcr and 5'bcr probes using Southern blot hybridization technique. Bcr rearrangements were detected in 8 patients with CML in the chronic phase, and bcr rearrangement was deduced to have existed in a CML patient in blastic crisis. However, no abnormal fragment was found in the patient with erythroleukemia. 3'bcr and 5'bcr probes combined with proper restriction enzymes were believed to be of great value in determining bcr rearrangements in Ph positive CML.
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PMID:BCR rearrangements in Ph positive chronic myelocytic leukemia. 168 Jun 11

The key enzymes in the formation of eicosanoids, including leukocyte 5-lipoxygenase (5LX), platelet 12-lipoxygenase (12LX), reticulocyte 15-lipoxygenase (15LX), prostaglandin G/H synthase cyclooxygenase, and leukotriene A4 (LTA) hydrolase have been studied extensively in recent years. Little is known, however, about the regulation of these enzymes at the gene level. We have developed a quantitative polymerase chain reaction (PCR) assay to quantify the mRNAs for these five enzymes, as well as for cytoplasmic beta-actin (bACT) mRNA. Human erythroleukemia (HEL) cells, which display megakaryocytic/erythroid characteristics, were selected as a source of RNA to characterize the assay. These cells expressed mRNA for bACT, LTA, cyclooxygenase, and 12LX (in decreasing order). mRNA for 5LX and 15LX was undetectable. Bronchoalveolar lavage fluid cells obtained from asthmatic patients, primarily alveolar macrophages, contained mRNA for bACT, LTA, 5LX, cyclooxygenase, and 15LX (in decreasing order). Treatment of HEL cells with phorbol 12-myristate 13-acetate or steroid administration to asthmatic patients apparently selectively regulated certain of these target genes. The utility of this assay in quantifying mRNA for the various target genes in blood cells, including platelets from patients with chronic myelogenous leukemia, has also been demonstrated. Studies on the regulation of genes for enzymes involved in the leukotriene and prostaglandin biosynthetic pathways, especially when only small tissue samples are available, will be facilitated with this approach.
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PMID:Eicosanoid forming enzyme mRNA in human tissues. Analysis by quantitative polymerase chain reaction. 190 25

The effects of TPA (12-0-tetradecanoylphorbol-13-acetate) and RA (retinoic acid) were investigated on the cell lines HL60 (acute promyelocytic leukemia) and K562 (erythroleukemia) and on cells from patients with several kinds of leukemia. There were 14 cases of acute lymphocytic leukemia (ALL), 2 cases of chronic lymphocytic leukemia (CLL), 23 cases of acute myeloid leukemia (M1-M7), 5 cases of chronic myelocytic leukemia in blast crisis (CML-BC) and 2 mixed leukemias. In almost all of the cases examined, after TPA exposure cells from patients with proven myeloid leukemia became adherent to the substrate, while lymphoid leukemia cells remained in suspension, allowing the differentiation of lymphoid from myeloid blasts. The only exception was in one case of CLL, which had cells that became adherent with long filamental projections. In addition, increased phagocytosis following TPA exposure permitted characterization of M7 as this was the only myeloid leukemia negative for phagocytosis. Further discrimination between the subtypes of myeloid leukemia could be based on the increased lysozyme production seen after TPA in M4 and M5. Esterase positivity allowed the discrimination of M1 cells, which were negative before and after TPA treatment. In agreement with the results of other authors, TPA and RA led to independent ways of differentiation, granulocytic-like lineage and monocytic-like cells being favored by RA and TPA, respectively. The capacity of the same cell to differentiate into more than one lineage, depending on whether RA or TPA was used, was only seen in the present study with M3 cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Myeloid leukemia differentiation by phorbol ester and retinoic acid: a practical approach. 223 Nov 80

A monoclonal antibody, MRK20, in F(ab')2 form [MRK20-F(ab')2], which reacts with 85-kDa membrane protein in a doxorubicin (ADM)-resistant subline (K562/ADM) of human myelogenous leukemia cell line, K562, was examined for reactivity with 41 cultured human leukemia and lymphoma cell lines. None of these cell lines had ever been exposed to any anticancer agent in vitro except K562/ADM. The relative resistance index to various drugs was calculated by dividing the 50% growth-inhibitory concentration (IC50) of the test cell line by IC50 of K562 (the negative control in the antibody experiment). MRK20-F(ab')2 reacted with seven cell lines, KYO-1 derived from chronic myelogenous leukemia in blastic crisis (CMLbc), CMK from acute megakaryoblastic leukemia, HEL from erythroleukemia, P31/FUJ from acute monocytic leukemia, KOPM-28 from CMLbc, PL-21 from acute promyelocytic leukemia and K562/ADM. MRK20-F(ab')2 did not react with 34 other cell lines. All seven MRK20-F(ab')2-positive cell lines had relative resistance index values of 2 or more to anthracyclines (ADM, pyrarubicin, daunorubicin), mitoxantrone, etoposide, bleomycin, and pepleomycin. There was no distinct correlation between the reactivity to MRK20-F(ab')2 and a higher relative resistance index than 2 to vinca alkaloids, actinomycin-D, cisplatin, 4-hydroperoxycyclophosphamide, nimustine hydrochloride, methotrexate or cytarabine. These results indicate that MRK20-F(ab')2 detects a novel multidrug resistance to anthracyclines, mitoxantrone, etoposide, bleomycin and pepleomycin in cultured human leukemia and lymphoma cells.
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PMID:A novel multidrug resistance in cultured leukemia and lymphoma cells detected by a monoclonal antibody to 85-kDa protein, MRK20. 251 73


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