vitamin-b-12 and Primary-Myelofibrosis

Topics: Antineoplastic Agents; Bone Marrow Examination; Folic Acid; Histamine; Humans; Hypertension, Portal; Immunoglobulins; Lymph Nodes; Primary Myelofibrosis; Prognosis; Splenectomy; Uric Acid; Vitamin B 12

Topics: Alpha-Globulins; Blood Proteins; Bone Marrow; Bone Marrow Cells; Carrier Proteins; Cobalt Radioisotopes; Evaluation Studies as Topic; Humans; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocytes; Polycythemia Vera; Primary Myelofibrosis; Protein Binding; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Aneuploidy; Basophils; Blood Platelets; Cell Transformation, Neoplastic; Child; Clinical Enzyme Tests; Cytogenetics; Eosinophilia; Fetal Hemoglobin; Fever; Hematologic Diseases; Humans; Leukemia, Myeloid; Leukocyte Count; Lymphatic Diseases; Muramidase; Primary Myelofibrosis; Prognosis; Skin Manifestations; Thrombocytosis; Vitamin B 12

To determine if increased cell turnover in chronic myeloproliferative disorders can lead to hyperhomocysteinemia as a result of folate and/or cobalamin depletion, and contribute to oxidative stress.. The clinical role of oxidative stress was investigated by measuring reactive oxygen species (ROS), total antioxidant capacity (TAC), and total homocysteine (tHcy), folate, cobalamin, and holotranscobalamin (HoloTC) levels in 51 chronic myeloproliferative disorders patients (male-to-female ratio: 1.1; median age: 64 years; range, 40-84 years), including 42 with primary myelofibrosis and 9 with post-polycythemia vera myelofibrosis.. Myelofibrotic patients had higher tHcy (p = 0.0201) and an unbalanced oxidative status (higher ROS and lower TAC levels; p < 0.0001) than controls. Presence of diabetes or another neoplasia was associated with higher ROS levels (p < 0.05), splenomegaly, hepatomegaly, and peripheral blasts with lower HoloTC levels (p < 0.005). The most severe forms of myelofibrosis (2-3) were associated with lower TAC (p = 0.045) and HoloTC levels (p = 0.017). Patients with Janus kinase-2 mutations had lower HoloTC levels (p = 0.0059). HoloTC deficiency was more frequently associated with Janus kinase-2 homozygosity (p < 0.0003).. Our findings suggest that the determination of HoloTC, tHcy, ROS concentrations, and TAC, can identify latent cobalamin deficiency and provide a rational basis for correcting the increased oxidation associated with disease progression.

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Chronic Disease; Female; Folic Acid; Homocysteine; Humans; Janus Kinase 2; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Mutation; Oxidative Stress; Polycythemia Vera; Polymorphism, Single Nucleotide; Primary Myelofibrosis; Reactive Oxygen Species; Transcobalamins; Vitamin B 12

A nine-year-old girl without aggravating family history or adverse pregnancy and neonatal outcome, who underwent a resection of the end section of the small bowel as a result of atresia in the first twenty four hours of her life, was admitted to the Department on account of spastic paresis of the lower extremities. Apathy and tiredness appeared the most striking features on the physical examination of the child; likewise the pale colour of skin and a scar on the abdomen integuments--a result of the resection. Neurological examination revealed pyramidal syndrome from the lower extremities, disturbed sense of balance with intensified with closed eyes, and deep sensibility disorders. Megaloblastic anaemia was revealed on further examination, while bone marrow image showed normoblastic erythropoiesis with the presence of megaloid cells. The extremely low level of vitamin B12 in the blood serum and a regular level of folic acid were found. The vitamin B12 absorption test (Schilling test) showed considerable impairment in the process. The inflammation of the esophagus and duodenum mucosa was confirmed in a histopathological examination. Furthermore, irregular result of somatosensory induced potentials (SEP) and conductivity test revealed some characteristics of axonal--demyelinating neuropathy in the lower extremities. MRI of the head and spinal cord was correct. The diagnostics excluded methylomalonic acidosis, multiple sclerosis and other causes of ataxia in children. The overall clinical picture, that is megaloblastic anaemia, the characteristics of the myelosis funicularis and interview data--resection of the bowel as well as other examinations confirmed that the observed disorders resulted from the impairment of vitamin B12 absorption. An appropriate treatment consisted of supplementation of vitamin B12 (intramuscular) and folic acid (orally) improved the neurological condition and hematologic parameters.. It is necessary to monitor hematologic parameters and the neurologic condition in the group of children who underwent the resection of the ileum in infancy. If vitamin B12 deficiency symptoms occur, appropriate treatment should be duly applied.

Topics: Anemia, Megaloblastic; Child; Female; Folic Acid Deficiency; Humans; Ileal Diseases; Infant; Intussusception; Malabsorption Syndromes; Primary Myelofibrosis; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adult; Anemia, Aplastic; Anemia, Pernicious; Diagnosis, Differential; Humans; Male; Primary Myelofibrosis; Reticulin; Vitamin B 12

In response to specific treatment of vitamin B12 deficient, anaemic patients there is an influx of folate into the young, circulating red cells. To separate new and old cells, capillary tubes filled with whole blood were centrifuged and the packed red cell column divided into top (T), middle (M) and bottom (B) layer. The newest cells are found in the T layer. The increase in red cell folate (RCF) concentration starts before, during or after the reticulocyte response, and is therefore not directly related to folate metabolism in the red precursor cells in the marrow. The low RCF concentration at the peak of the reticulocyte response in some of the cases demonstrates that the folate material, which may have been accumulated in the red precursor cells in the marrow, may be lost by the time the red cells enter the peripheral blood. The influx of folate into the young, circulating red cells is rapidly followed by an efflux of folate, suggesting that much of the folate material is still in the monoglutamate form. A new influx of folate is noted after a time lapse of from 5 to 10 d. Iron deficiency seems to prevent the uptake of folate by the circulating red cells.

Topics: Aged; Anemia, Pernicious; Erythrocytes; Female; Folic Acid; Humans; Hydroxocobalamin; L-Lactate Dehydrogenase; Male; Middle Aged; Primary Myelofibrosis; Pteroylpolyglutamic Acids; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Diagnosis, Differential; Humans; Leukemia, Myeloid; Primary Myelofibrosis; Vitamin B 12

Nine patients were selected according to the following criteria: 1. Hematological findings consistent with the diagnosis of myelofibrosis with myeloid metaplasia (MMM), except for an excess of blasts in the blood and bone marrow; 2. No previous (silent) phase of MMM. 3. No PH1 chromosome, and 4. No identifiable cause of secondary myelofibrosis. These patients had either an acute or subacute myelofibrosis. The onset of such symptoms as fever, bone pain, hemorrhage and mild splenomegaly was rapid. Terminal acute leukemia or more often progressive bone marrow biopsy showing myelofibrosis with persistence of differentiated myeloid tissue, particularly megacaryocytes. Isotopic studies (59Fe and 51Cr) showed splenic erythroid metaplasia, poor bone marrow 59Fe uptake and increased peripheral red blood cell destruction. This study confirms that malignant myelosclerosis is a well-defined syndrome which must be distinguished from: a) Acute transformation of typical agnogenic myeloid metaplasia even though it was previously undiagnosed (4 cases of MMM illustrating this possibility have been reported); b) Acute myeloblastic leukemia with myelofibrosis; and c) Myelofibrosis secondary to lymphomatous or carcinomatous bone-marrow invasion (2 cases with acute myelofibrosis appearing long after appropriate treatment have been reported).

Topics: Acute Disease; Adult; Aged; Alkaline Phosphatase; Bone Marrow Examination; Cell Survival; Erythrocytes; Erythropoiesis; Female; Folic Acid; Humans; Leukemia; Leukocytes; Male; Middle Aged; Primary Myelofibrosis; Uric Acid; Vitamin B 12

The hypothesis that transcobalamin I (TC I) originates from granulocytes was tested by comparing the isoelectric focusing (IEF) patterns of the R-type binder (cobalophilin) of vitamin B12 of: 1) lysed granulocytes, 2) 24 h granulocyte output, and 3) plasma. The preparations came from the blood of 5 normal subjects and 4 with myeloproliferative states. The cobalophilin released into a culture of granulocytes resembled the binder in the granulocytes initially. TC I, defined as the alpha1 cobalophilin with components isoelectric between pH 2.9-3.35 and as a carrier of native plasma B12, was not released by granulocytes. The granulocyte binder of leukaemic granulocytes did not differ from the normal in content per cell or amount released.

Topics: Blood Proteins; Cells, Cultured; Granulocytes; Humans; Isoelectric Focusing; Leukemia; Leukemia, Myeloid; Leukocytes; Primary Myelofibrosis; Transcobalamins; Vitamin B 12

The unsaturated vitamin B12 binding capacity of whole serum (UBBC) and of the three transcobalamins (TC) has been studied in patients with various haematological diseases including myeloproliferative disorders (MPD) and acute leukaemia. The binding capacity of TC I and TC III was increased in MPD; TC I being particularly high in chronic granulocytic leukaemia (CGL) and TC III especially raised in polycythaemia rubra vera (PRV) and in infectious leucocytosis. The binding capacity of both TC I and TC III correlated with blood neutrophil count and the ratio TC III/TC I was low in CGL and increased in PRV. TC II was increased in acute myelogenous leukaemia, during remission and blast cell crisis of CGL and in refractory anaemia with excess of myeloblasts but not in acute lymphoblastic leukaemia (ALL). TC II correlated inversely with blood neutrophil count. There is an inverse ratio between TC II and TC I at least in myelogenous leukaemia. These abnormalities are discussed in relation to granulocyte kinetics. TC III and TC I reflect probably the total body granulocyte pool and share some biochemical and immunological properties supporting the view that they have a common origin in the more mature stages of the granulocyte cell line while TC II probably originates partly in more primitive granulocytes.

Topics: Anemia, Aplastic; Blood Cell Count; Blood Proteins; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukocyte Count; Leukocytosis; Myeloproliferative Disorders; Neutrophils; Polycythemia Vera; Primary Myelofibrosis; Transcobalamins; Vitamin B 12

Topics: Aged; Diagnosis, Differential; Humans; Leukemia, Myeloid; Leukocyte Count; Male; Primary Myelofibrosis; Vitamin B 12

Topics: Adult; Anemia, Pernicious; Chronic Disease; Female; Humans; Infant, Newborn; Leukemia, Myeloid; Male; Maternal-Fetal Exchange; Multiple Myeloma; Myeloproliferative Disorders; Placenta; Polycythemia Vera; Pregnancy; Primary Myelofibrosis; Vitamin B 12

Topics: Alpha-Globulins; Autoradiography; Beta-Globulins; Blood Proteins; Chromatography, DEAE-Cellulose; Cobalt Isotopes; Humans; Leukemia, Myeloid; Leukocytes; Polycythemia Vera; Primary Myelofibrosis; Protein Binding; Vitamin B 12

Topics: Anemia; Anemia, Hypochromic; Anemia, Macrocytic; Anemia, Pernicious; Blood Proteins; Female; Hematologic Diseases; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocyte Count; Liver Cirrhosis; Lupus Erythematosus, Systemic; Lymphoma; Male; Multiple Myeloma; Neoplasms; Polycythemia; Primary Myelofibrosis; Protein Binding; Uremia; Vitamin B 12

Topics: Adolescent; Adult; Alkaline Phosphatase; Anemia; Bone Marrow Examination; Busulfan; Chromosome Aberrations; Female; Humans; Leukemia, Myeloid; Leukocytes; Male; Middle Aged; Primary Myelofibrosis; Prognosis; Radiometry; Splenomegaly; Technetium; Thrombocytopenia; Vitamin B 12

Topics: Adult; Cobalt Isotopes; Humans; Intestinal Absorption; Male; Primary Myelofibrosis; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Agammaglobulinemia; Agranulocytosis; Anemia; Anemia, Hemolytic; Anemia, Hypochromic; Anemia, Macrocytic; Anemia, Sideroblastic; Antineoplastic Agents; Bone Marrow Diseases; Elliptocytosis, Hereditary; Female; Folic Acid; Folic Acid Deficiency; Humans; Iron; Myeloproliferative Disorders; Polycythemia Vera; Pregnancy; Primary Myelofibrosis; Spherocytosis, Hereditary; Thalassemia; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Hemolytic; Anemia, Pernicious; Hodgkin Disease; Humans; Leukemia; Lymphoma, Non-Hodgkin; Malabsorption Syndromes; Polycythemia Vera; Primary Myelofibrosis; Radioisotope Dilution Technique; Schilling Test; Vitamin B 12

Topics: Alpha-Globulins; Beta-Globulins; Bone Marrow Diseases; Diagnosis, Differential; Female; Hematologic Diseases; Humans; Leukemia, Myeloid; Polycythemia Vera; Pregnancy; Pregnancy Complications, Hematologic; Primary Myelofibrosis; Prognosis; Protein Binding; Uremia; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adolescent; Adult; Aged; Alkaline Phosphatase; Bone Marrow Diseases; Chromosome Aberrations; Chromosome Disorders; Chromosomes, Human, 1-3; Chromosomes, Human, 13-15; Chromosomes, Human, 4-5; Chronic Disease; Diagnosis, Differential; Female; Hemorrhage; Hemostasis; Hepatomegaly; Humans; Leukemia, Myeloid; Leukocytes; Male; Megakaryocytes; Middle Aged; Myeloproliferative Disorders; Polycythemia Vera; Primary Myelofibrosis; Splenomegaly; Thrombocytosis; Vitamin B 12

Topics: Anemia, Hemolytic, Autoimmune; Basophils; Blood Platelet Disorders; Bone Marrow; Chromosome Aberrations; Chromosome Disorders; Diagnosis, Differential; Female; Humans; Karyotyping; Leukemia, Myeloid; Leukocytosis; Middle Aged; Primary Myelofibrosis; Vitamin B 12

Topics: Humans; Leukemia; Primary Myelofibrosis; Vitamin B 12

Topics: Adult; Aged; Alkaline Phosphatase; Blood Chemical Analysis; Chromosome Aberrations; Chromosome Disorders; Chromosomes; Diagnosis, Differential; Female; Humans; Leukemia, Myeloid; Liver; Male; Middle Aged; Primary Myelofibrosis; Vitamin B 12

Topics: Alkaline Phosphatase; Anemia; Anemia, Hypochromic; Blood; Cobalt Isotopes; Erythropoiesis; Folic Acid; Folic Acid Deficiency; Histidine; Humans; Iron; Primary Myelofibrosis; Tritium; Vitamin B 12; Vitamin B Deficiency

Topics: Anemia; Anemia, Macrocytic; Anemia, Pernicious; Avitaminosis; Clinical Laboratory Techniques; Female; FIGLU Test; Folic Acid; Folic Acid Deficiency; Formiminoglutamic Acid; Geriatrics; Glutamates; Humans; Maternal-Fetal Exchange; Metabolism; Pregnancy; Primary Myelofibrosis; Urine; Vitamin B 12; Vitamin B Deficiency

Topics: Anemia; Anemia, Pernicious; Cobalt Isotopes; Corrinoids; Diagnosis, Differential; Hematinics; Humans; Neurologic Manifestations; Primary Myelofibrosis; Vitamin B 12; Vitamin B Complex