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)

Sixty-three bone marrow (BM) and peripheral blood specimens from patients with platelet counts of 1000 x 10(9)/L or greater were examined in an attempt to determine if any BM or peripheral blood findings could be used reliably to distinguish primary thrombocythemia from other myeloproliferative disorders and extreme examples of reactive thrombocytosis. Our results indicated that the BM findings in primary thrombocythemia were quite similar to those in polycythemia vera and chronic granulocytic leukemia with associated extreme thrombocytosis. However, statistically significant differences between the BM findings in myeloproliferative disorders and extreme reactive thrombocytosis were found in the numbers of megakaryocytes, presence or absence of megakaryocyte clusters, stainable iron, cellularity, and reticulin content. We concluded that BM examination is a useful procedure as an aid in determining the cause of extreme thrombocytosis.
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PMID:Bone marrow and peripheral blood findings in patients with extreme thrombocytosis. A report of 63 cases. 202 16

The iron-binding proteins lactoferrin (LF) and H-ferritin have been implicated in the negative regulation of myelopoiesis in vitro and in vivo. The present studies evaluated the functional activity of affinity-purified LF from polymorphonuclear neutrophils (PMN) of patients with chronic myelogenous leukemia (CML) and LF/H-ferritin-cell interactions in a nonleukemic patient with LF deficiency with normal levels of circulating blood leukocytes. Affinity-purified CML-PMN-LF was found to be qualitatively deficient as a suppressor of the release of colony-stimulating factors from mononuclear blood cells, adding to previous information from our group documenting defective LF-cell interactions in CML. LF was detected by immunoradiometric assay in PMN of the patient with LF deficiency, but at a much lower level than normal. This LF was found, however, to be active as a suppressor molecular against the patient's cells and normal donor cells. Patient cells were as responsive as normal cells to effects of purified milk LF. Decreased LF levels in this patient were associated with increased levels of monocyte H-ferritin inhibitory activity, consistent with the known suppressive effects in vitro of LF on H-ferritin release from monocytes. Patient marrow hematopoietic progenitor cells were as responsive as progenitors from normal donors to suppression by purified H-ferritin and prostaglandin E1. These results are consistent with a role of LF and H-ferritin in the control of myelopoiesis in this patient.
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PMID:Qualitative functional deficiency of affinity-purified lactoferrin from neutrophils of patients with chronic myelogenous leukemia, and lactoferrin/H-ferritin-cell interactions in a patient with lactoferrin-deficiency with normal numbers of circulating leukocytes. 204 67

The effect of the divalent hydrophobic metal chelator 1,10-phenanthroline was evaluated alone and in combination with the antineoplastic agent hydroxyurea on human chronic myeloid leukemia cells. The compound at concentrations of 10 and 5 micrograms/ml significantly (p less than 0.001) potentiates DNA biosynthesis inhibiting the activity of hydroxyurea in vitro. Synergistic inhibition was obtained when both 1,10-phenanthroline and hydroxyurea was used in combination at relatively nontoxic concentrations. Cytotoxicity due to the combination was found to be partially reversible and was marginally reversible in the presence of Fe+2 and Zn. The results strongly suggest the utility of the iron-chelating agent along with hydroxyurea for further evaluation to achieve a better therapeutic result in the clinic.
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PMID:1,10-phenanthroline potentiates cytotoxicity of hydroxyurea in human chronic myeloid leukemia cells. 271 31

The iron chelator desferrioxamine (DFO) has been previously shown to be an S-phase inhibitor of cell proliferation. To investigate its potential as an antileukemic drug, we first studied the effects of DFO on the in vitro growth of normal human hematopoietic progenitors (CFU-GM and BFU-E) and clonogenic cells from human leukemic cell lines. Then we evaluated the effects of DFO on progression of leukemia refractory to conventional therapy in two individuals. Micromolar concentrations of DFO determined a dose-dependent inhibition of normal progenitor growth, with inhibitory dose 50% (ID50) for CFU-GM and BFU-E being 6.7 and 5.5 microM/liter, respectively. Marked inhibitory effects were observed on clonogenic cells from HL-60 (ID50 = 1.4 microM/liter) and U-937 (ID50 = 3.6 microM/liter) human leukemic cell lines grown in semisolid medium. When DFO was given intravenously to a patient with lymphoid blast crisis of chronic myelogenous leukemia, a marked reduction in circulating blast count was observed. On the contrary, no in vivo effect was observed in a patient with acute nonlymphocytic leukemia having transfusional iron overload. We conclude that: (a) DFO is an inhibitor of both normal and leukemic myeloid cell proliferation in vitro; (b) our limited in vivo observations and a previous case study suggest that intravenous administration of DFO to patients with normal to low plasma iron may result in leukemic cytoreduction in vivo.
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PMID:Effects of desferrioxamine on normal and leukemic human hematopoietic cell growth: in vitro and in vivo studies. 291 Dec 2

The effect of hydroxyurea (HU) was studied in 15 cases of human chronic myeloid leukemia cells (CML) in combination with iron-chelating agent, 2,2-bipyridine (bipyridine). The extent of (3H)thymidine incorporation in CML cells in vitro was taken as an index for the measurement of cytotoxicity. In the present study, we observed a potentiation in HU cytotoxicity by hydrophobic iron-chelator bipyridine (p less than 0.001) resulting in complete DNA biosynthesis inhibition. Both HU and bipyridine were used at a relatively non-toxic concentrations of 10(-4) M and 10 micrograms/ml, respectively. This inhibition was found to be partially reversible and a partial protective action by iron is also demonstrated. The various other metal chelators failed to sensitise CML cells to HU cytotoxicity. Implications with respect to the efficacy in cancer treatment is discussed.
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PMID:Potentiation of hydroxyurea cytotoxicity in human chronic myeloid leukemia cells by iron-chelating agent. 309 95

The cytotoxic effect of caracemide and hydroxyurea was compared in human chronic myeloid leukemia cells. Caracemide was found to be about twelve times more effective than hydroxyurea. The combined effect of caracemide, hydroxyurea and hydrophobic iron-chelating agents at relatively nontoxic concentrations was studied. Hydroxyurea, 2,2'-bipyridine and 1,10-phenanthroline combined with caracemide synergistically inhibited DNA synthesis, while Desferal did not show any such effect. Fe++ partially reversed the cytotoxicity of caracemide in combination with 2,2'-bipyridine, while it had no effect on the cytotoxicity of caracemide alone. Caracemide was found to have a stronger inhibitory effect on DNA synthesis in P388 lymphocytic leukemia and Ehrlich ascites carcinoma cells than hydroxyurea. However, bipyridine, phenanthroline and Desferal in combination with caracemide did not induce any synergistic inhibition. These data indicate the value of human tumor cells to predict drug responsiveness and suggest the further evaluation of caracemide and its combination with hydroxyurea and iron-chelating agents in the treatment of human leukemias.
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PMID:In vitro cytotoxicity of caracemide alone and in combination with hydroxyurea or iron-chelating agents in human chronic myeloid leukemia cells and murine tumors. 316 54

We have developed a technique that permits evaluation and semi-quantification of iron-binding function in mature neutrophils. Neutrophil iron-binding reactivity (NFeBR) visualized using the iron nitrilotriacetate-acid ferrocyanide technique was rated 0 to 5+ in 100 segmented cells; the ratings were totaled to yield a score (NFeBRS). Males and post-menopausal females had significantly higher NFeBRS than pre-menopausal females. Neonates had low values, and a homogeneous distribution of NFeBR among neutrophils. In pregnancy and acute infection, NFeBRS were significantly increased. In a patient with congenital lactoferrin (Lf) deficiency, the NFeBRS was very low. In Ph1-positive chronic myelogenous leukemia, 13 of 17 patients had low NFeBRS due to decreased NFeBR, which was heterogeneously distributed among mature neutrophils. By ultrastructural analysis of mature neutrophils in two such patients, the stain deposits in FeBR-positive granules were of normal intensity, but the numbers of positive granules were decreased in many cells. NFeBRS were also low in 12 of 23 patients with other myeloproliferative disorders, and in seven of 15 patients with acute non-lymphoblastic leukemia, but in only seven of 63 patients with other neoplasms. NFeBRS were significantly correlated (p less than 0.008) with values of neutrophil Lf content quantified by immunologic assays in a wide variety of conditions and over a broad range of values. These results augment observations of neutrophil Lf made using immunological methods.
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PMID:Iron-binding reactivity in mature neutrophils: relative cell content quantification by cytochemical scoring. 336 50

Stainable iron was absent or decreased in 36 of 45 bone marrow biopsy specimens (80 percent) among 33 patients with chronic-stage chronic granulocytic leukemia. Decreased iron did not correlate with sex, treatment status, duration of disease, marrow cellularity, or hemoglobin level. In contrast, marrow iron was absent or decreased in 34 percent of biopsy specimens at diagnosis of acute nonlymphocytic leukemia (p less than 0.0001) and 31 percent of biopsy specimens from patients with Hodgkin's disease (p less than 0.0001). The serum ferritin level was determined in eight patients with chronic granulocytic leukemia and absent marrow iron, and it was normal in all. Fifteen of 17 patients, followed with chronic-stage disease for one to four years after the finding of absent marrow iron, demonstrated increases in their hemoglobin levels during antileukemic therapy or maintained normal values. Thus, absent or decreased stainable marrow iron is a common finding in chronic granulocytic leukemia and usually does not indicate iron deficiency.
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PMID:Decreased stainable marrow iron in chronic granulocytic leukemia. 346 10

High serum ferritin levels without any correspondence to the amount of total body storage iron have been found in patients with leukemia. Investigating 96 adults with different types of leukemia, we found that serum ferritin can be used as a tumor marker in myeloid leukemias. Extremely high serum ferritin levels were seen in acute myeloblastic leukemia before treatment and in blastic crisis of chronic myeloid leukemia (ie, 21-fold increased serum ferritin concentrations). Patients with acute myeloblastic leukemia in complete remission had their ferritin concentrations decreased to normal. A relapse of the disease was paralleled by a repeated increase of serum ferritin level. In patients with chronic myeloid leukemia during the chronic phase we found normal serum ferritin concentrations, whereas blast crisis was associated with highly raised serum ferritin levels. We conclude that serum ferritin concentration must be valued as a clinically useful tumor marker in these types of leukemia, exhibiting a helpful and simple parameter in monitoring the activity of the disease.
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PMID:Ferritin--a tumor marker in myeloid leukemia. 386 36

Backscattered Electron Imaging (BEI) is a particular technique which permits to study cytochemical reactions with the Scanning Electron Microscope (SEM). The BEI data pertaining to specific enzymatic activities can be directly correlated to the surface morphology of each individual cell. Leukocytes from 5 normal individuals, 14 patients with acute nonlymphoblastic leukaemia (ANLL), 7 patients with chronic myeloid leukaemia (CML) and 3 patients with acute lymphoblastic leukaemia (ALL) were studied for myeloperoxidase activity, acid phosphatase localization, silver staining of the nuclei and phagocytosis of iron carbonyl in the BEI mode of SEM. Some normal peripheral blood leukocytes which cannot be distinguished by their surface morphology alone were satisfactorily identified with the BEI technique. Leukaemic myeloid cells can be recognized in many cases because of their positive myeloperoxidase reaction, while monocytic elements can be characterized by the presence of surface ruffles, acid phosphatase activity and active phagocytosis. The usefulness of the BEI technique in identifying different blood cell types with the SEM and its possible application to the diagnosis of certain cases of leukaemia are discussed.
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PMID:Scanning electron microscope cytochemistry of normal and leukaemic leukocytes. 632 37


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