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)

Basic red cell ferritin was investigated in 28 patients with different phases of chronic granulocytic leukemia (CGL). Red cell ferritin was significantly decreased in remission after busulphan treatment and significantly elevated in the blast crisis as compared to healthy controls. Bone marrow stainable iron was decreased or absent in 86% of patients in the initial phase at the time of diagnosis and in 92% of those in remission. Red cell ferritin correlated with serum ferritin, however, serum ferritin level remained above normal range during all phases of the disease. A negative correlation between red cell ferritin and hemoglobin (Hb) (r = -0.605, p < 0.001) suggested that red cell ferritin level reflected the rate of iron utilization for heme synthesis. Decreased red cell iron stores observed in the remission may be explained by regression of dyserythropoiesis and by restoration of normal Hb synthesis after busulphan treatment. A progressive dyserythropoiesis in the blast crisis may lead to an increased red cell ferritin level.
 ...
PMID:Red cell ferritin and iron stores in chronic granulocytic leukemia. 793 95

Greater than 80% of patients in the stable phase of chronic myelogenous leukemia (CML) have no detectable stainable iron in the marrow yet have normal serum iron, total iron binding capacity, and serum ferritin values. We studied the pattern of marrow iron in 187 marrow aspirates from 67 patients with Philadelphia chromosome positive CML in the chronic, accelerated and blast crisis stages. Sequential marrow aspirates in 30 patients confirm that the switch from negative iron to positive iron is coincident with the development of the accelerated phase of blast crisis of CML. Our data suggest that the pattern of marrow iron staining in CML is a useful prognostic indicator of the disease evolution.
 ...
PMID:Correlation of marrow iron patterns with disease status of chronic myelogenous leukemia. 840 Nov 82

The level of iron responsive element-binding protein (IRE-BP) in leukemic cells, which is essential for iron homeostasis and plays an important role in cell metabolism and cell growth, was measured using an enzyme-linked immunosorbent assay (ELISA). Comparing the levels in different clinical stages, the levels in CML cells in the chronic phase (mean +/- S.E., 0.270 +/- 0.110 U/mg protein, n = 9) and those in AML cells (0.150 +/- 0.104 U/mg) protein, n = 21) were significantly lower than that in normal granulocytes (0.628 +/- 0.216 U/mg protein, n = 9, p < 0.001 vs CML and AML). Analysis of IRE-BP mRNA expression in leukemic cells using semiquantitative polymerase chain reaction showed suppressed expression of mRNA as compared to normal bone marrow cells. These observations suggest that there may be dysregulation of IRE-BP expression and production in leukemic cells.
 ...
PMID:Iron responsive element-binding protein (IRE-BP) in leukemic cells: analysis using enzyme-linked immunosorbent assay and semiquantitative polymerase chain reaction. 841 98

Idic(X)(q13) represents a rare but recurrent chromosomal abnormality in haematological malignancies. We present five new cases characterized by this particular aberration and review the literature on this subject. The patients were elderly females with a diagnosis of refractory anaemia (1/5), refractory anaemia with ringed sideroblasts (2/5), chronic myelomonocytic leukaemia (1/5), and Philadelphia chromosome-negative chronic myeloid leukaemia (1/5). Three out of the five patients demonstrated an increased proportion of bone marrow ringed sideroblasts. After a follow-up period of 30-57 months all patients but one are alive. Idic(X)(q13) always occurred as the sole chromosomal abnormality, either in one or in two copies. We confirmed the dicentric nature of the aberration by fluorescence in situ hybridization (FISH) on metaphases as well as interphase nuclei using an X-chromosome-specific alpha-satellite probe, and performed chromosome painting to visualize possible additional chromosomal changes involving the X chromosomes. Our findings and the data of 17 previously published cases indicate that idic(X)(q13): (1) may play a significant pathogenetic role in haematological malignancies affecting exclusively females and deriving predominantly from early progenitor cells; (2) is frequently associated with a pathological iron accumulation; (3) indicates a variable prognosis.
 ...
PMID:Isodicentric (X)(q13) in haematological malignancies: presentation of five new cases, application of fluorescence in situ hybridization (FISH) and review of the literature. 854 34

This report suggests modest changes in the criteria used for the diagnosis of ET and allows tentative recommendations concerning therapy. As outlined in Table I, we believe that absent stainable marrow iron does not necessarily indicate iron deficiency in these patients and that the serum ferritin and RBC mean corpuscular volume should be incorporated in this assessment. Normal values speak strongly against iron-deficient erythropoiesis. A search for the bcr/abl gene rearrangement should be included with the marrow karyotype to exclude CML. Finally, cytogenetic data and morphologic study of the marrow should be used to be certain that a MDS should not be considered. It may be that measurements of serum thrombopoietin levels may be useful in the future. Nonetheless, in principle, ET remains a diagnosis of exclusion as we have originally suggested. For therapy, HU remains an excellent choice for the older patient at risk for thrombosis. Nonetheless, no myelosuppressive therapy remains a perfectly viable option, particularly for the young patient and the older with low thrombotic risk. The roles of anagrelide and alpha interferon in this setting have not been fully defined. Experience with both has still been relatively short. It would be ideal if prospective, randomized trials could be mounted to address these questions. We conclude with confidence that return to older approaches such as 32P and AA in patients who fail on HU is to be discouraged. The use of anagrelide or interferon alfa seems to be a much more appropriate approach. We have not investigated the role of antithrombotic agents such as aspirin in ET. In PV, the combination of aspirin, 300 mg three times daily, and dipyridamole, 75 mg three times daily, failed to reduce the rate of thrombosis and was associated with an increased rate of hemorrhage. It is rational to suggest that lower doses of aspirin (ie, < 325 mg daily) might be associated with less hemorrhage and, perhaps, a beneficial effect on thrombosis. This remains to be shown.
 ...
PMID:Experience of the Polycythemia Vera Study Group with essential thrombocythemia: a final report on diagnostic criteria, survival, and leukemic transition by treatment. 902 60

We investigated the role of ceruloplasmin in the antioxidative process in the brain in a patient with hereditary ceruloplasmin deficiency (HCD). Immunohistochemistry revealed an accumulation of Nepsilon-(carboxymethyl) lysine (CML) in basal ganglia of the HCD brain. In vitro study disclosed that ceruloplasmin inhibited CML formation from glycated proteins through the reaction of Fe2+ with H2O2 by Fenton reaction. These data suggest that ceruloplasmin plays an important role in the protection of neurons against oxidative stress associated with iron metabolism.
 ...
PMID:Hereditary ceruloplasmin deficiency increases advanced glycation end products in the brain. 1044 2

Differentiation of an elevated, repeatedly determined platelet count (> or =500x10(9)/l) includes the discrimination between reactive causes generated by a variety of underlying conditions and a neoplastic myeloproliferative disorder (CMPD). In addition to clinical findings, the evolution of laboratory data during follow-up and histology of the bone marrow exerts a significant diagnostic impact. Characteristic features are not only expressed by hematopoiesis, but also by the myeloid stromal compartment. While the megakaryocyte-rich subtype of chronic myeloid leukemia (CML) and the 5q(-) syndrome (MDS) are dominated by abnormal micromegakaryocytes, in polycythemia vera (PV) this cell lineage reveals a pleomorphous appearance. In essential thrombocythemia (ET), a prevalence of giant megakaryocytes with deeply lobulated (staghorn-like) nuclei may be encountered. A clear-cut discrimination of ET from early (hypercellular) stages of idiopathic (primary) myelofibrosis (IMF) presenting with thrombocythemia becomes possible, provided the conspicuous atypical features of megakaryopoiesis characterizing the latter entity are taken into account. Moreover, CML displays a predominance of the granulocytic lineage whereas PV shows a panmyelosis or trilineage proliferation, involving erythropoiesis, in particular. In contrast, erythropoiesis is markedly reduced in CML and to a lesser degree also in IMF. In CMPDs extreme values of iron deposits may be found, ranging from a total lack (PV) to minor amounts (CML) and a normal staining reaction (ET). Similar results are exhibited regarding reticulin fibrosis, which is usually not present in ET, rarely observed in PV and detectable to a variable degree in CML and IMF.
 ...
PMID:[Thrombocytosis versus thrombocythemia--differential diagnosis of elevated platelet count]. 1066 67

An immunohistochemical and morphometric study was performed on bone marrow biopsies in 604 patients with chronic myelogenous leukemia (CML) to compare morphological and clinical features and to evaluate effects of interferon (IFN) and chemotherapy. Following morphometry significant correlations were calculated between number of CD61(+) megakaryocytes, including their precursors with fiber density. This finding is in line with the close functional relationship between megakaryopoiesis and fibroblasts regarding the complex pathomechanism of myelofibrosis. The latter was observed in about 28% of patients already at diagnosis. In a similar way, the frequency of CD68(+) macrophages was correlated with the amount of Ret40f(+) nucleated erythroid precursors, implicating an involvement of this cell lineage in iron turnover, hemoglobin synthesis, and degradation of the expelled nuclei from normoblasts. The (alpha-D-galactosyl residue-expressing) Pseudo-Gaucher cells were detectable in 30% of pretreatment specimens. Moreover, significant associations were calculable between reduction in erythropoiesis or increase in fibers with clinical features such as hemoglobin level, percentages of myelo- and erythroblasts in the peripheral blood, and spleen size. These variables are in keeping with more advanced stages of CML. Based on our morphometric evaluations, a classification into three different histological subgroups: granulocytic, megakaryocytic, and myelofibrotic was carried out. This simplified staging system was correlated with corresponding sets of hematological data. Sequential biopsies in 173 patients with monotherapy by IFN, hydroxyurea (HU), or busulfan (BU) revealed a fibrogenic effect of IFN in contrast to a fiber-reducing property of HU. The dynamics of myelofibrosis and changes of major cell lineages during treatment were readily demonstrable by calculating corresponding indices. These included the ratios between quantitative differences of corresponding variables at repeated examinations and time. Thus, in patients with complete hematological remission following IFN administration, regeneration of erythropoiesis was found to be accompanied by an increase in the total number of CD68(+) macrophages, including activated subpopulations. Histological subgroups showed a transition from a (nonfibrotic) granulocytic and megakaryocyte pattern to the myelofibrotic subtype in about 40% of patients. This change was opposed to a numerical reduction in the myelofibrotic subtype which occurred in 17 patients (36%), but predominantly in those under HU therapy. In conclusion, the striking heterogeneity of bone marrow features in CML warrants a careful morphological evaluation of trephine biopsies and appropriate means of processing to achieve relevant correlations with clinical data and, thus, allows a more elaborate insight into the dynamics of the disease process.
 ...
PMID:[Histologic and hematological findings in CML. A comparative immunohistochemical-morphometric and clinical study on bone marrow biopsies from 604 patients derived from two institutes of pathology (Cologne/Freiburg)]. 1066 68

A multicenter, immunohistochemical and morphometric study was performed on diagnostic pretreatment bone marrow biopsies in 614 adult patients with Ph1+ chronic myeloid leukemia (CML) to compare histological features with clinical findings. For identification of megakaryopoiesis we used the monoclonal antibody CD61 and additionally the PAS reaction to determine the subfraction of atypical micromegakaryocytes and precursors. Labelling of erythroid precursors was carried out by a monoclonal antibody directed against glycophorin C. In order to selectively stain macrophages and their activated subset we applied CD68 and the GSA-I lectin. Density of argyrophilic fibers (reticulin plus collagen) was measured following Gomori's silver impregnation method. In accordance with laboratory data morphological variables revealed a comparable amount of congruence in the various groups of CML patients derived from different sources. In about 26% of patients early (reticulin) to advanced (collagen) fibrosis was detectable. Significant correlations were calculated between the extent of myelofibrosis with splenomegaly, anemia and increasing numbers of erythroblasts and myeloblasts in the peripheral blood count. These features were assumed to indicate more advanced stages of the disease process with ensuing transition into myeloid metaplasia and consequently were associated with an unfavorable prognosis. Significant relationships were revealed between the number of CD61+ megakaryocytes and more important, also their precursor fraction with the degree of fibrosis. This result extends previous experimental findings regarding the impact of immature elements of this cell lineage for the generation of myelofibrosis. The significant association of erythroid precursors with the number of mature (resident) macrophages including their activated GSA-I subset may shed some light on their functional involvement in iron turnover and hemoglobin synthesis. A modified histological classification of predominant bone marrow features is introduced. This simplified synthesis staging system (Cologne Classification) is not only associated with certain sets of laboratory data, but also with different survival patterns.
 ...
PMID:Bone marrow features and clinical findings in chronic myeloid leukemia--a comparative, multicenter, immunohistological and morphometric study on 614 patients. 1067 1

METHODS: Evaluated are surgical difficulties, management problems and weight loss in patients with distal gastric bypass as a revisionary procedure. Eighty patients were followed up to 3 years; four were lost to follow-up. Mean age was 43; mean prebariatric surgery weight 134 kg; height 1.65 meters; body mass index 40.1; ideal body weight 62.7 kg; excess weight 70.5 kg; per cent excess weight 214%. A 250 cm stomach-to-ileocecal valve segment of small bowel was used, and the biliopancreatic secretions were brought into the terminal ileum 100 6 in from the ileocecal valve. Mean pouch size was 63 cc; length of hospital stay 5 days; operative blood loss 616 cc; operative time 130 min. RESULTS: Intraoperative complications included three splenic injuries (without splenectomy). Early complications included one deep vein thrombosis, two marginal ulcers, one GI hemorrhage, one wound dehiscence, one pouch outlet obstruction and one pancreatitis. Late complications included: one death from protein malnutrition/ ARDS; 21 hypoproteinemia; six protein malnutrition, and of these, three had hyperalimentation; three cholecystitis; 27 anemia; 22 incisional hernia; two staple-line disruption (reoperated); 26 low serum iron; 11 prolonged (>6 months) diarrhea; three prolonged frequent vomiting; and two unrelated deaths (chronic myelogenous leukemia and amyotrophic lateral sclerosis). Mean excess weight loss was 83% at 12 months; 89% at 24 months; and 94% at 36 months. CONCLUSION: The distal gastric bypass is fraught with the operative and immediate post-operative complications experienced in any revisionary bariatric surgery. Distal gastric bypass is very effective in producing long-term weight loss. Nutritional problems are common but usually easily corrected. The most serious nutritional complication is protein malnutrition, which must be identified and corrected early. Success of this procedure is dependent upon patient compliance with proper nutrition and supplements, and regular office follow-up with monitoring of laboratory data. Patients who are noncompliant are at significant risk for complications.
 ...
PMID:The Gastric Bypass for Failed Bariatric Surgical Procedures. 1072 55


<< Previous 1 2 3 4 5 6 7 8 Next >>