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)

1. Low serum B12 levels can be measured with considerable precision by microbiological assay with the Euglena gracilis assay and B12 deficiency can be recognised with a high level of consistency by either the Euglena or L. leichmannii assays. Either method is ideally suited for the assay of large numbers of specimens. The Lactobacillus leichmanii technique requires preliminary extraction of protein and it has been suggested that this may be a source of inaccuracy. 2. The radioisotope dilution assay should be the ideal method of measuring B12 levels in small or moderate numbers of specimens for it is a simple method that can be carried out in any laboratory with suitable counting equipment. After many false starts the conditions required for accurate assay are now understood. Each of 40 to 50 radioisotopic dilution techniques that have been introduced claims to be capable of differentiating B12 deficiency from control subjects but the reported correlations between the actual levels found in the two different assays are variable and the levels may be much higher with some radioisotopic methods. 3. The subnormal serum levels which are found in pernicious anaemia with all these techniques indicate severe reduction of the liver B12 level. A low serum B12 level in other conditions has, in the absence of associated folate or iron deficiency, the same significance. If the fall in the serum B12 level is associated with folate or iron deficiency, the tissue B12 levels are usually reduced but not to the low levels found in B12 deficiency states. 4. In practice, a subnormal B12 level is a valuable pointer not only to unsuspected pernicious anaemia but also to other gastrointestinal or nutritional disorders. The significance of a fall in the B12 level can only be understood if its cause is defined by a full clinical and gastroenterological investigation. 5. Falsely low serum B12 levels are found under certain iatrogenic conditions and B12 levels may be normal in spite of cellular deficiency of B12 under the rare circumstances of pernicious anaemia being associated with chronic myeloid leukaemia or when there is deficiency of TC 2.
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PMID:The serum vitamin B12 level: its assay and significance. 82 83

The human leukemias are a group of hematologic neoplasms characterized by uncontrolled proliferation of cells concerned with blood cell production. The cause(s) of human leukemia remains unknown. Bone marrow (BM) is believed to be the site of origin of human leukemias, although the specific locus(i) and/or cell(s) from which it arises have not been definitively identified. Generally, human leukemias and related proliferative diseases are thought to be clonal in nature; affecting a single hematopoietic stem cell, which then proliferates and replaces the marrow of normal hematopoietic stem cell systems. The condition is believed to be malignant in nature. Results of our current morphologic studies on well-fixed, ideally-stained thin sections of plastic-embedded bone marrow biopsies (BMB) from a large number of acute (AML, ALL) and chronic (CGL, CLL) leukemia patients suggest that human leukemias may not be clonal diseases. Instead, a large population of other resident cells--'endosteal cells'--appears to become involved in the process and it is possible that all members of this group enter the activity simultaneously. This change (transformation) in the endosteal cell population might be due to an abnormality (qualitative or quantitative) of diffusable, humoral factors (yet to be identified) that are responsible for the growth and proliferation of these hematopoietic precursor cells. In this context, the human leukemias may be considered not as malignant, but rather the result of an aberration of factor(s) that control hematopoiesis. In this respect, the human leukemias, particularly AML, ALL and CML, might be analogous to pernicious anemia (megaloblastic anemia) as it was understood 40-50 years ago.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The origin and spread of human leukemia. 143 86

Sera from 39 patients with pernicious anemia and 251 patients with various other diseases and 42 healthy normal subjects were tested for intrinsic factor blocking antibody by a Corning commercial kit. Twenty-five (64%) out of 39 pernicious anemia patients showed a positive reaction to the intrinsic factor blocking antibody. The positive incidence of intrinsic factor blocking antibody by this method agreed well with the results obtained in this laboratory over the past 10 years using the charcoal method. No sera from normal subjects tested were positive for the intrinsic factor blocking antibody. All 226 sera with vitamin B12 levels less than 3,500 pg/ml which came from patients without pernicious anemia, were negative for the intrinsic factor blocking antibody. In 15 sera with B12 levels greater than 3,500 pg/ml from patients who received recent B12 medications, 11 sera showed false positive results. On the other hand, no false positive results were obtained by this method in 10 sera with endogenous serum B12 levels greater than 3,500 pg/ml collected from patients with chronic myelogenous leukemia. It is reasonable to presume that this assay is clinically useful for detection of intrinsic factor blocking antibody in the diagnosis of pernicious anemia, if false positive results due to B12 medication are excluded.
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PMID:Evaluation of a new assay kit for intrinsic factor blocking antibody (type I) as an aid in the diagnosis of pernicious anemia. 407 44

The bone marrow biopsy specimens of 35 patients with benign and malignant erythroid hyperplasias were examined for the presence of hemoglobin A, hemoglobin F, muramidase (lysozyme), and transferrin, using an indirect immunoperoxidase method (PAP) on Zenker's-fixed paraffin-embedded bone marrow biopsy specimens and particles. Five cases of each of the following entities were studied: erythroleukemia and erythremic myelosis, acute granulocytic leukemia with maturation (FAB M2), polycythemia rubra vera, myeloproliferative syndrome in childhood, megaloblastic anemia (B12 and folate deficiency), erythroid hyperplasia (regenerating bone marrow and hemolytic anemia), and Ph' chromosome positive chronic granulocytic leukemia. Hemoglobin A was present in both the early and late erythroid precursors in all conditions. Hemoglobin F was the predominant hemoglobin in early erythroblasts of pernicious anemia and in both early and late erythroid elements in erythroleukemia and erythremic myelosis. Small quantities of hemoglobin F were present in a few isolated clusters in other conditions. Staining for hemoglobin F may be useful in identifying immature erythroid precursors and in distinguishing some cases of dysplastic erythroid hyperplasia from neoplasia. Additionally, these findings suggest that the maturational switch in hemoglobin synthesis operates with distinct pathways under different conditions.
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PMID:An immunohistochemical study of hemoglobin A, hemoglobin F, muramidase, and transferrin in erythroid hyperplasia and neoplasia. 619 99

The cobalamin metabolism in chronic myelogenous leukemia (CML) was evaluated in 18 newly diagnosed and untreated patients by formiminoglutamic acid (FiGlu) and methyl malonic acid excretion (MMA) tests. A deoxyuridine (dU) suppression test of bone marrow cells was compared in patients with acute myelogenous leukemia (N = 5), myelodysplastic disease (N = 3), untreated pernicious anemia (N = 16), folate deficiency (N = 7), and a hospital reference group without signs of cobalamin or folate deficiency (N = 22). All had normal MMA excretion but 3 of 15 patients had increased FiGlu excretion. In vitro thymidine uptake in bone marrow cells of CML patients were lower (mean 40 fmol/106 cells) than pernicious anemia patients (115 fmol/106 cells). Methotrexate (MTX) increased the uptake in all cases. Addition of formyl-THF, methyltetrahydrofolate (methyl-THF), and pteroylglutamic acid (PGA) tended to normalize the effect of MTX. In pernicious anemia methyl-THF only decreased the uptake in combination with CN-Cbl. dU suppression values were significantly higher (6.3%) in CML than in the reference group (4.4%), but significantly lower than in pernicious anemia (41.6%) and folate deficiency (28.5%). The dU suppression values in bone marrow cells of CML patients correlated significantly with the transferrin saturation. In buffy coat cells dU suppression values were even higher (9.3%) than in bone marrow cells of the same CML patients. Addition of folate forms and CN-Cbl did not change the dU suppression values in CML, as it did in pernicious anemia. MTX increased dU suppression values significantly in all patients, but more in CML (64.5%) than in pernicious anemia (48.6%) and controls (49.8%). The MTX effect was to some extent neutralized by folate analogues with formyl-THF as the most effective followed by methyl-THF and lastly PGA. Methyl-THF also neutralized MTX in pernicious anemia, but its effect was certainly enhanced by addition of CN-Cbl. Thymidine uptake and dU suppression patterns were not significantly changed in CML after treatment with busulfan for 1 week or in accelerated phase. We concluded that signs of cobalamin or folate deficiency (apart from one patient) cannot be demonstrated in untreated CML. However, dU suppression was significantly increased and more so in circulating myeloid cells than in bone marrow. This indicates a deranged metabolism of deoxynucleotides which is independent of cobalamin and folates, and a difference between bone marrow cells and circulating cells. dU suppression is a valuable indicator of cobalamin deficiency.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cobalamin-dependent metabolism in chronic myelogenous leukemia determined by deoxyuridine suppression test and the formiminoglutamic acid and methylmalonate excretion in urine. 777 63

A morphometric analysis has been performed on bone marrow trephine biopsies following sequential double-immunostaining with monoclonal antibodies PC10 (anti-proliferating cell nuclear antigen--PCNA) and Y2/51-CD61 (anti-platelet glycoprotein IIIa) to evaluate endoreduplicative activity of megakaryopoiesis. In addition to a control group, patients included different subtypes of chronic myeloproliferative disorders (CMPDs) like chronic myeloid leukaemia (CML), polycythaemia vera (P. vera), primary thrombocythaemia (PTH) and finally primary (idiopathic) osteomyelofibrosis (OMF). In comparison with the normal bone marrow and also with P. vera and PTH a significant increase in PCNA-labelling (late G1 and S phases) of megakaryocytes was recognizable in OMF, contrasting with a striking reduction of this marker in CML. Particularly in advanced stages of OMF, secondary folate deficiency leading to a megaloblastoid appearance of erythroid precursors is a frequent finding. In pernicious anaemia previous cytokinetic studies have demonstrated an arrest in the S phase (DNA synthesis) of the cell cycle due to vitamin B12/folate (haematinic) deficiency. A similar pathomechanism may also be effective in OMF. Consequently, a block in the S phase of the cell cycle is assumed which is in keeping with the increased numbers of PC10-positive megakaryocytes. Significant correlations were calculable between megakaryocyte sizes and PCNA-staining capacity in the normal bone marrow and CMPDs. According to morphometry small-sized (hypoploid) megakaryocytes showed a prevalence of PCNA labelling. This finding is confirmative with a hypothesis on the dynamics of endoreduplicative activity of megakaryocytes, i.e. the prolongation of G1/G2 phases in larger (polyploid) elements. On the other hand, some of the giant polyploid megakaryocytes may cease endoreduplication and enter into G0 phase, which could partially explain the predominance of PCNA-negative large-sized cells of this lineage.
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PMID:Megakaryopoiesis in chronic myeloproliferative disorders: immunohistochemical evaluation of endoreduplicative activity by PCNA-staining reaction. 798 Nov 37

Cell cycle stage distribution of bone marrow cells was studied at flow cytometry in 137 hematological patients. They had acute lymphoblastic leukemia, acute myeloblastic leukemia, lymphosarcoma with leukemization, blast crisis of chronic myeloid leukemia, iron deficiency anemia, pernicious anemia, autoimmune hemolytic anemia, aplastic anemia (31, 34, 18, 12, 17, 8, 9, 8 cases, respectively). It was found that in leukemia, and to a lesser degree in anemia, stability of the cell cycle was impaired. In leukemia onset, recurrence and remission, the proportion S/(G2+M) appeared increased evidencing defective DNA synthesis by myelokaryocytes and ineffective hemopoiesis. Similar changes were seen in pernicious and aplastic anemia.
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PMID:[Changes in the stability of the parameters of the bone marrow cell cycle in hematologic diseases]. 942 52

The family planning program is not restricted to population control; it also aims at the wider aspect of family welfare and human health. A large number of human diseases are due to genetic abnormalities. Examples are mongolism (Down's syndrome), ovarian dysgenesis (Turner's syndrome), nonfunctional testes (Klinefelter's syndrome), chronic myeloid leukemia, anemia, thalassemia, congenital malformations, and schizophrenia. Mental defects include imbeciles and the feebleminded. Constitutional diseases include diabetes, idiopathic epilepsy, pernicious anemia, and some thyroid abnormalities. Some chronic diseases also have a significant genetic component in their etiology, such as asthma and other allergies. About half of the stillbirths and embryonic wastage are suspected of being due to genetic malformations. Consanguinity has an important bearing on malformations and developmental anomalies. In India, where consanguinity is more frequent, malformations per 1000 births were 8.6 and 3.1 in 2 centers studied. Neural tube defects, harelip, cleft palate, and malformations of the gut and of limbs were prevalent. The population that needs genetic counseling is not large. Persons suffering from hereditary dise ases having a high risk of transmission should be advised to refrain fro m having children. A correct diagnosis, complete family history, and kn owledge of the literature on inherited disease is needed by the counselo rs. Family planning programs should include genetic counseling.
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PMID:Genetic counselling in family planning. 1225 20

There is lack of information about the relative prevalence of haematological disorders in Yemen and other Middle East countries. The aim of this study was to evaluate the pattern of haematological diseases diagnosed by bone marrow examination in Yemen considering the limited diagnostic facilities. At the referral haematology centre in Yemen, between November 1999 and November 2005, 785 patients >14 years old were evaluated by bone marrow examination. Relevant investigations were performed when needed. A total of 627 patients had haematological disorders other than lymphoma, and their data were analysed. There were 273 females and 354 males. A total of 159 patients had Acute myeloid leukaemia, 75 had acute lymphocytic leukaemia, 87 had chronic myeloid leukaemia, 36 chronic lymphocytic leukaemia, eight had multiple myeloma, 13 myelodysplastic syndromes, seven myelofibrosis, seven polycythaemia vera, three primary thrombocythaemia, two hairy cell leukaemia, two metastases, 36 aplastic anaemia, 29 immune thrombocytopenic purpura (ITP), nine autoimmune haemolytic anaemia, three pernicious anaemia, 65 iron deficiency anaemia, 57 megaloblastic anaemia and malaria, 18 mixed deficiencies, and 11 patients had visceral leishmaniasis. Sex- and age-related distribution of the various disorders was also presented. In conclusion, the leukaemias were the most frequently encountered diagnosis followed by iron deficiency anaemia, megaloblastic anaemia and malaria, aplastic anaemia and ITP respectively. The other haematological disorders were less common. These findings are comparable with that seen in other developing and developed countries.
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PMID:Pattern of haematological diseases diagnosed by bone marrow examination in Yemen: a developing country experience. 1710 90

Autoimmune conditions are associated with an elevated risk of lymphoproliferative malignancies, but few studies have investigated the risk of myeloid malignancies. From the US Surveillance Epidemiology and End Results (SEER)-Medicare database, 13 486 myeloid malignancy patients (aged 67+ years) and 160 086 population-based controls were selected. Logistic regression models adjusted for gender, age, race, calendar year and number of physician claims were used to estimate odds ratios (ORs) for myeloid malignancies in relation to autoimmune conditions. Multiple comparisons were controlled for using the Bonferroni correction (P<0.0005). Autoimmune conditions, overall, were associated with an increased risk of acute myeloid leukaemia (AML) (OR 1.29) and myelodysplastic syndrome (MDS, OR 1.50). Specifically, AML was associated with rheumatoid arthritis (OR 1.28), systemic lupus erythematosus (OR 1.92), polymyalgia rheumatica (OR 1.73), autoimmune haemolytic anaemia (OR 3.74), systemic vasculitis (OR 6.23), ulcerative colitis (OR 1.72) and pernicious anaemia (OR 1.57). Myelodysplastic syndrome was associated with rheumatoid arthritis (OR1.52) and pernicious anaemia (OR 2.38). Overall, autoimmune conditions were not associated with chronic myeloid leukaemia (OR 1.09) or chronic myeloproliferative disorders (OR 1.15). Medications used to treat autoimmune conditions, shared genetic predisposition and/or direct infiltration of bone marrow by autoimmune conditions, could explain these excess risks of myeloid malignancies.
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PMID:Risks of myeloid malignancies in patients with autoimmune conditions. 2733 45


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