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

Quantitative whole-body linear profile scans of 59Fe, obtained by a whole-body counter, conventional ferrokinetics and hematological parameters are investigated in patients (n = 208) with various hematological-oncological diseases. Linear whole-body profile scans in controls, obtained 24 h after i.v. injection of 59Fe-transferrin, give quantitative information about sites of the erythropoietic system. Early profile scans (1 h p.i.) in patients with anemia show a typical 'iron-suction' corresponding to the fast outflow of 59Fe from the blood compartment. We found no typical change of iron distribution in Hodgkin and Non-Hodgkin lymphomas, even in patients with anemia or hemolysis there was no evidence of expansion of erythropoiesis to distal marrow sites. Our investigation does not contribute to staging of patients with Hodgkin's disease. Osteomyelofibrosis is characterized by a centrifugally expanded erythropoiesis. The value of increased iron uptake 24 h p.i. in leg regions for differential diagnosis of hemolytic anemia, chronic myelocytic leukemia, and pancytopenia where a similar pattern of iron distribution is observed will be discussed. Quantitative iron kinetics with one dimensional 59Fe profile scans give additional information in patients with displaced erythropoietic system.
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PMID:[Ferrokinetics in 1-dimensional whole-body profiles in hematologic diseases]. 640 12

We examined the synthesis of lactoferrin, an iron binding protein that, among hematopoietic cells, is restricted to secondary granules of polymorphonuclear leukocytes. Lactoferrin biosynthesis was absent from leukemic myeloblasts and promyelocytes but abundant in normal bone marrow and both the bone marrow and peripheral blood of patients with chronic myelogenous leukemia (CGL) if the samples contained substantial numbers of myelocytes and metamyelocytes. Lactoferrin was present in the steady state in normal or CGL bands and polymorphonuclear leukocytes, but no lactoferrin biosynthesis was detectable in these samples. Taken together, these results suggest that lactoferrin accumulation begins with the onset of biosynthesis at the myelocyte stage and is largely complete by the beginning of the band stage of maturation. HL-60 cells, a permanent promyelocytic leukemia cell line, synthesized no lactoferrin. Translation of messenger RNA in Xenopus laevis oocytes revealed that mRNA from patients with chronic myelogenous leukemia and abundant myelocytes and metamyelocytes directed the synthesis of readily detectable amounts of lactoferrin, whereas HL-60 cells contained no translatable lactoferrin mRNA. We thus hypothesize that lactoferrin is a useful marker of gene expression restricted to the terminal stages of granulocyte maturation. Biosynthesis of this protein appears to be mediated by appearance of translatable mRNA at the myelocyte stage, coincident with development of secondary granules. Absence of lactoferrin production by HL-60 cells is due to absence of translatable lactoferrin mRNA, either because of lineage infidelity of these transformed cells or because of arrest before the developmental stage at which secondary granules appear.
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PMID:Lactoferrin biosynthesis during granulocytopoiesis. 659

In the process of evaluating roles for purified preparations of lactoferrin, transferrin and acidic isoferritins in the regulation of myelopoiesis, it was found that: (1) values reported for lactoferrin in the serum and plasma of normal donors are in most cases an over-estimation, (2) lactoferrin suppresses the production/release of granulocyte-macrophage colony stimulatory factors (GM-CSF) from monocytes in the absence of T-lymphocytes and also suppresses the production/release of acidic isoferritin-inhibitory activity from monocytes, (3) lactoferrin, transferrin and acidic isoferritins act on their specific target cells which express Ia-like antigens, (4) lactoferrin and transferrin act in vivo to suppress rebound myelopoiesis in mice recovering from sublethal dosages of Cytoxan, with preliminary observations suggesting that lactoferrin has a greater apparent effect on the bone marrow and transferrin has a greater apparent effect on the spleen, (5) active lactoferrin derives from Fc receptor positive subpopulations of PMN from patients with CML as well as from normal donors, but the percentage of Fc receptor containing PMN is lower in CML, as is the amount of active lactoferrin found in their PMN, and (6) lactoferrin, transferrin and acidic isoferritins suppress the colony formation of U937 clonogenic cells, with lactoferrin and transferrin decreasing the release of growth factors from U937 cells which are needed to stimulate U937 colony formation, and lactoferrin and acidic isoferritins suppress the colony formation of WEHI-3 cells, with lactoferrin decreasing the release of growth factors from WEHI-3 cells which are needed to stimulate WEHI-3 colony formation. Speculation on the potential usefulness of these iron binding glycoproteins to control of disease progression is given in the discussion.
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PMID:Lactoferrin, transferrin and acidic isoferritins: regulatory molecules with potential therapeutic value in leukemia. 660 37

The records on 375 consecutive bone marrow aspirations were reviewed to establish the incidence and association of peripheral and bone marrow basophilia. Seventeen cases of peripheral basophilia were identified (4.5 percent incidence) and were associated with iron deficiency (five cases), lung carcinoma (four cases), anemia of undetermined cause (four cases), and chronic myelogenous leukemia, myelodysplasia, chronic renal failure, and acute myelogenous leukemia (one case each). There were six cases of marrow basophilia, including iron-deficiency anemia (two cases), sideroblastic anemia with myelodysplasia, mild dyspoiesis, anemia of chronic disease, and acute erythroleukemia. Marrow basophilia was significantly associated with myelodysplasia and sideroblastic anemia, but was not found in 37 patients with lymphoproliferative disorders. There were no instances of simultaneous marrow and peripheral basophilia. These data support the concept that marrow basophilia is a specific, although not sensitive, marker of disruption of the normal marrow maturation controls.
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PMID:Basophils in peripheral blood and bone marrow. A retrospective review. 670 76

Ferritin was prepared from the leucocytes of four patients with acute myeloblastic leukaemia (AML) and eight patients with chronic myeloid leukaemia (CML). Isoelectric focusing demonstrated a prominent relatively basic band in all the CML cell ferritins. The iron content of all the ferritins was very low (max 180 atom/molecule). Thus there was little evidence for the role of leucocyte ferritin as an iron store or for iron as the major factor responsible for the initiation of ferritin synthesis. The iron uptake properties, subunit analyses, immunological reactivities and other immunological studies indicated that leukaemic cell ferritins had similar properties to tissue ferritins.
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PMID:Biochemical and immunological characterization of ferritin from leukaemic cells. 677 79

In order to study the pathogenesis of juvenile-type chronic myelocytic leukemia (CML), we examined the colony-forming capacity and colony composition in the bone marrow (BM) and peripheral blood (PB) of three children with juvenile-type CML. Large numbers of granulocytes and macrophage colonies were formed by BM and PB cells. Whole agar culture staining revealed that especially macrophage colonies increased in comparison with normal controls. After removal of carbonyl iron-laden cells with a magnet or deprivation of cells adherent to glass from BM cells, the number of macrophage colonies markedly reduced in comparison with the number of colonies formed by untreated BM cells, suggesting that some of the macrophage colony-forming cells (M-CFC) may have phagocytic and/or adherent activity. Radiation sensitivity and thymidine suicide rate of these M-CFC were not different from those of granulocyte colony-forming cells (G-CFC). The predominance of M-CFC in juvenile-type CML may be one of the reflections of fetal-type myelopoiesis since M-CFC are predominant in cord blood and PB in the neonatal period. Moreover, considerable numbers of erythroid-colony-forming units (CFU-E) were present in PB of all patients. It may be concluded that juvenile-type CML is a panmyelopathy with the predominance of M-CFC.
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PMID:Characterization of hemopoietic precursor cells in juvenile-type chronic myelocytic leukemia. 695 Nov 3

Acidic isoferritins have been identified as leukemia-associated inhibitory activity (LIA), which suppresses colony and cluster formation of colony-forming unit-granulocyte macrophages from normal donors but not from patients with leukemia. LIA was detected in all ferritin preparations tested, including ferritin isolated from normal heart, spleen, liver, and placental tissues, and from the spleens of patients with chronic myelogenous leukemia and Hodgkin's disease. Purified preparations of LIA were composed almost entirely of acidic isoferritins, as determined by immunoassay, radioimmunoassay, and isoelectric focusing. The inhibitory activity in the LIA and ferritin samples was inactivated by a battery of antisera specific for ferritin, including those prepared against acidic isoferritins from normal heart and spleen tissues from patients with Hodgkin's disease, and those previously absorbed with basic isoferritins. Antisera absorbed with acidic isoferritins did not inactivate the inhibitory activity. Separation of LIA and chronic myelogenous leukemia and normal spleen ferritin by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and isoelectric focusing confirmed that the regions of peak inhibitory activity corresponded in each to an apparent molecular weight of approximately 550,000 and to a pI value of 4.7. Similar physicochemical characteristics included inactivation by methods that dissociate ferritin molecules into subunits and by treatment with trypsin, chymotrypsin, pronase, and periodate. The purified preparations were extremely stable to heat treatment. The glycoprotein nature of the inhibitory activity was substantiated because it bound to concanavalin A-Sepharose and was eluted off by alpha-methyl mannose. Inhibitory activity of the activity of the acidic isoferritins was detected at concentrations as low as 10(-17)-10(-19) M and iron saturation did not appear to be necessary for its action. These results implicate acidic isoferritins in the regulation of normal myelopoiesis and suggest a role for them in the progression of leukemia.
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PMID:Identification of leukemia-associated inhibitory activity as acidic isoferritins. A regulatory role for acidic isoferritins in the production of granulocytes and macrophages. 697 99

Primary F1 hybrid anti-parent T cell-mediated lympholysis (F1 alpha P CML), induced in mixed spleen cell cultures, is an immune response specific for self H-2 antigens. The cellular requirements for induction were investigated by depleting or enriching stimulator splenocytes of adherent/phagocytic cells. Relatively large numbers of parental cells that are adherent to Sephadex G-10 particles or to plastic surfaces, and phagocytic for carbonyl iron, were required for stimulation (approximately 10(5) purified stimulators for 3.5 X 10(6) responders). Such parental cells are resistant to gamma radiation (in vivo and in vitro) and hydrocortisone (in vivo), negative for Thy-1, and positive for I-A and I-E/C surface antigens. This subpopulation of macrophages includes the predominant or sole immunogenic parental cell type of the spleen for the F1 alpha P response. Whereas removal of adherent/phagocytic cells from parental splenocytes entailed loss of stimulatory activity for F1 responder T lymphocytes, this was not the case for allogeneic responders. The ability to induce allogeneic CML was, in fact, fully retained by depleted parental cells. Adherent/phagocytic cells of F1 responder origin were available for cellular interactions in all mixed spleen cultures, yet they were competent for presentation of alloantigens, but not of self antigens borne by parental cells other than macrophages. In conclusion, the cellular requirements for stimulation differ quantitatively and qualitatively in F1 alpha P CML as compared to allogeneic and other CML systems. The distinct requirements presumably relate to the generation of specific effectors that are autoreactive as opposed to reactive with foreign antigens.
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PMID:Requirement of adherent/phagocytic cells for the induction of F1 anti-parent cell-mediated lympholysis. I. Parental adherent splenocytes serve as stimulators. 702 8

Organ toxicity in BMT may in part be due to free radical damage. Therefore the 'Total Radical-trapping Antioxidant Parameter of plasma' (TRAP), individual plasma antioxidants, serum iron and linoleic acid, a main substrate of lipid peroxidation, were monitored before and after BMT, and they were compared with values obtained from healthy controls. Seven patients (3 AML, 3 CML, 1 multiple myeloma) receiving 16 mg/kg busulfan, 30-45 mg VP-16 and 120 mg/kg cyclophosphamide were investigated. TRAP values declined during chemotherapy by about 40% (day -9: 1019 +/- 245 mumol/l, mean +/- s.d.; day 0: 660 +/- 164 mumol/l; P < 0.05). The concentration of uric acid, one of the main antioxidants in plasma, decreased markedly (day -9: 339 +/- 108 mumol/l, day 0: 148 +/- 61 mumol/l; P < 0.05) and paralleled TRAP values. Vitamin E and bilirubin did not change from day -9 to 0 whereas vitamin C increased (day -9: 46 +/- 16 mumol/l, day 0: 89 +/- 44 mumol/l; P < 0.05). Serum iron rapidly increased within the pre-transplantation period, reaching values normally seen only in iron overload (day -9: 11.8 +/- 5.2 mumol/l, day 0: 40.6 +/- 6.5 mumol/l; P < 0.05). Linoleic acid levels were normal at the start and decreased substantially (27.0 +/- 1.6 wt% at day -9; 15.7 +/- 4.9 wt% at day 0; P < 0.05), indicating possible lipid peroxidation during high-dose chemotherapy. In conclusion, complex monitoring of the antioxidant status before and after BMT revealed a breakdown of plasma antioxidant defence and of radical-vulnerable lipids, which was associated with high circulating levels of iron.
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PMID:Deteriorating free radical-trapping capacity and antioxidant status in plasma during bone marrow transplantation. 767 Apr 3

An immunohistochemical and morphometric analysis was performed on trephine biopsy specimens in 60 patients with chronic myeloid leukemia (CML) to quantify erythropoiesis and its proliferation capacity and to assess the stainable marrow iron (hemosiderin). For this purpose, an elaborate double-immunostaining technique was applied. This included a monoclonal antibody (PC10) that is directed against proliferating cell nuclear antigen (PCNA), followed by an antibody against glycophorin C (Ret40f), to identify all nucleated erythroid precursor cells. Additionally, morphometric data were derived from immunostaining of megakaryocytes (CD61) and macrophages (PG-M1), including its hemosiderin-laden subpopulation. Finally the determination of argyrophilic (reticulin) fiber density was carried out. In comparison with a control group (15 patients) without any hematologic disorder, in CML patients morphometric evaluation showed a significant reduction in the number of erythroblasts and normoblasts. This feature was associated with a PCNA-labeling index within the normal range and a decreased stainable marrow iron (number of hemosiderin-storaging macrophages). Several parameters were established to exert a predictive value on survival. A worsening of prognosis was associated with a decrease in the number of erythroid precursors (< 460/mm2), a low hemoglobin level (< 10 g/dl), a high megakaryocyte count (> 50 cells/mm2), an increased density of reticulin fibers (> 30 i x 10(2)/mm2) and splenomegaly (> 15 cm below costal margin). Our findings are in keeping with results obtained from in vitro studies of cell proliferation in CML, which is not significantly altered in comparison with the normal bone marrow. Finally, the present data, although derived from a small group of patients, emphasize the impact of histologic variables to be included in one of the major clinical trials on prognosis in CML.
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PMID:Erythropoiesis in CML--immunomorphometric quantification, PCNA-reactivity, and influence on survival. 790 86


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