vitamin-b-12 and Leukemia--Myeloid--Acute

Acute leukaemia (AL) has been observed in association with Crohn's disease (CD) notably in patients treated with azathioprine (AZA), which is an immunosuppressant known for its carcinogenicity and in particular known to induce therapy-related acute myeloid leukaemia according to the 2008 WHO classification. Whereas the link between inflammatory bowel disease and AL has been well established, the exact role of AZA remains controversial. In this paper, we report the case of a 71-year-old white Caucasian male with CD treated for 7 years with AZA who developed an acute leukaemia. Chemotherapy was administered unsuccessfully and the patient died from this haematological disorder 9 months after diagnosis. We reviewed the current evidence on the interactions between CD, AL and AZA as well as the potential underlying mechanisms of leukaemia in AZA-treated patients. From this review, we concluded that AL should be questioned when facing cytopenia in a patient with CD. The nature of the association between AZA and AL in CD patients warrants further investigation.

Topics: Aged; Antineoplastic Agents; Azathioprine; Bone Marrow; Chromosome Aberrations; Crohn Disease; Humans; Immunophenotyping; Immunosuppressive Agents; Karyotyping; Leukemia, Myeloid, Acute; Male; Vitamin B 12

Topics: Anemia, Aplastic; Anemia, Macrocytic; Antineoplastic Agents; Bone Marrow; Hematopoietic Stem Cells; Humans; Leukemia, Myeloid, Acute; Metaplasia; Preleukemia; Prognosis; Syndrome; Vitamin B 12

Topics: Cell Division; Drinking; Folic Acid; Granulocytes; Humans; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Lithium; Protein Binding; Texas; Vitamin B 12

Acute promyelocytic leukemia (APL) is characterized by proliferation of morphologically abnormal promyelocytes and a severe bleeding diathesis. The abnormal promyelocyte is characterized by abundant, large granules, many of which are spindle-shaped. Electron microscopic appearance of the granules closely resembles that of Auer rods. The granules appear to possess tissue thromboplastin activity by both immunologic and clotting assays. Coagulation studies in APL are generally consistent with disseminated intravascular coagulation. Prolongation of the prothrombin time and elevation of fibrinogen degradation products are the tests that are most commonly abnormal. Although occasional reports indicate a favorable response of the coagulopathy to drugs that inhibit fibrinolysis, the use of prophylactic heparin appears to be the treatment of choice. The response rate of APL to chemotherapy regimens that contain an anthracycline is comparable to that of acute myelogenous leukemia. The recent description of the 15;17 chromosomal translocation which may be pathognomonic for APL is only the second example of a chromosomal marker of human neoplasia. Marked elevation of serum vitamin B12 and B12 binding proteins appears to be another characteristic feature of APL. An in vitro cell line of APL cells has been demonstrated to have the capacity to differentiate to functional polymorphonuclear leukocytes, but the cause for the maturation arrest is unknown.

Topics: Blood Coagulation Disorders; Bone Marrow; Cell Line; Chromosome Banding; Daunorubicin; Fibrinogen; Fibrinolysis; Hemorrhage; Heparin; Humans; Leukemia, Myeloid, Acute; Prognosis; Prothrombin Time; Thromboembolism; Vitamin B 12

Acute promyelocytic leukemia is a form of acute myeloblastic leukemia characterized by hemorrhagic episodes, severe thrombocytopenia and infiltration of the marrow with "hypergranular" promyelocytes, often with multiple Auer bodies. Ultrastructurally. the promyelocytes show many splinter granules and Auer bodies with characteristic hexagonal arrangement of tubules with a periodicity of 250 A. Serum vitamin B12 and B12-binding proteins, in particular, transcobalamin I, are abnormally high. Karyotypic abnormalities include pseudodiploidy and partial deletion of the long arm of chromosome 17. Coagulation profile during bleeding episodes is usually consistent with disseminated intravascular coagulation. Greatly improved prognosis in recent years as a result of aggressive chemotherapy and anticoagulation emphasizes the need of early recognition of this clinical entity.

Topics: Adult; Bone Marrow; Hemorrhagic Disorders; Humans; Karyotyping; Leukemia, Myeloid, Acute; 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: Adult; Antimetabolites, Antineoplastic; Bone Marrow Transplantation; Female; Humans; Injections, Spinal; Leucovorin; Leukemia, Myeloid, Acute; Magnetic Resonance Imaging; Methotrexate; Peripheral Blood Stem Cell Transplantation; Prednisone; Spinal Cord; Spinal Cord Diseases; Vitamin B 12

Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy whose incidence is growing in developed countries. In the relapse setting, very limited therapeutic options are available and in most cases only palliative care can be offered to patients. The effect of a composite formulation that contains several antioxidants, Ocoxin Oral solution (OOS), was tested in this condition. When analyzed in vitro, OOS exhibited anti-AML action that was both time and dose dependent. In vivo OOS induced a ralentization of tumor growth that was due to a decrease in cell proliferation. Such effect could, at least partially, be due to an increase in the cell cycle inhibitor p27, although other cell cycle proteins seemed to be altered. Besides, OOS induced an immunomodulatory effect through the induction of IL6. When tested in combination with other therapeutic agents normally used in the treatment of AML patients, OOS demonstrated a higher antiproliferative action, suggesting that it may be used in combination with those standard of care treatments to potentiate their antiproliferative action in the AML clinic.

Topics: Animals; Antioxidants; Apoptosis; Ascorbic Acid; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Female; Folic Acid; Humans; Leukemia, Myeloid, Acute; Mice; Mice, Nude; Pantothenic Acid; Plant Extracts; Random Allocation; Vitamin B 12; Vitamin B 6; Xenograft Model Antitumor Assays; Zinc Sulfate

Topics: Anemia; Humans; Leukemia, Myeloid, Acute; Male; Neutropenia; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia; Anemia, Megaloblastic; Biomarkers, Tumor; Diagnosis, Differential; Erythroblasts; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Neutropenia; Severity of Illness Index; Vitamin B 12; Vitamin B 12 Deficiency

Vitamin B12 deficiency can cause profound alterations in the bone marrow. These alterations can mimic the more serious diagnosis of acute leukemia. The two patients described in this report were originally suspected of having acute leukemia or myelodysplasia on the basis of the bone marrow smear, and induction chemotherapy was considered. However, after further studies, they were both found to have vitamin B12 deficiency, and parenteral vitamin B12 administration resulted in normalization of the bone marrow.

Topics: Aged; Anemia, Pernicious; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Myelodysplastic Syndromes; Vitamin B 12

Megaloblastic anemia (MA) due to vitamin B12 deficiency is a reversible form of ineffective hematopoiesis. Myelodysplastic syndrome (MDS) is an acquired, irreversible disorder of ineffective hematopoiesis, characterized by stem cell dysfunction as a consequence of DNA damage manifested in part by karyotype anomalies. Importantly, MA and MDS are generally considered mutually exclusive diagnoses. We report the case of a 73-year-old woman with a profound macrocytic anemia, monocytosis and neurologic symptoms. Low cobalamin levels and the presence of anti-intrinsic-factor antibodies definitively established a diagnosis of pernicious anemia. Replacement therapy resulted in resolution of neurologic findings and macrocytosis; however, the anemia and monocytosis persisted. Bone marrow biopsy revealed trilineage myelodysplasia, which together with the peripheral monocytosis suggested a diagnosis of chronic myelomonocytic leukemia. Karyotype analysis revealed a clone with 45, XX, +der(1;7)(q10;p10)-7 [20]. Eighteen months after documented vitamin B12 replenishment her MDS transformed to terminal acute myeloid leukemia with the same clonal abnormality. Reversible cytogenetic abnormalities have been observed with MA, occasionally including karyotypes typically associated with MDS or myeloid leukemias. These abnormalities, like the anemia, resolve with vitamin replacement. This case suggests that MA and MDS can occur simultaneously; clinicians should be aware that this phenomenon occurs. Whether acquired karyotype abnormalities from the MA were related to the MDS and subsequent myeloid leukemia in this woman is a speculative but intriguing consideration that is discussed.

Topics: Aged; Anemia, Pernicious; Autoantibodies; Biopsy; Bone Marrow; Chromosome Aberrations; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 7; Female; Humans; Intrinsic Factor; Karyotyping; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes; Vitamin B 12

A nonisotopic assay of vitamin B-12 in human serum or plasma is described, performed with the Abbott IMx analyzer. The sample is first treated at pH > 12.5 to release bound vitamin B-12 and to convert all forms to cyanocobalamin. Next, the analyte is bound, at lower pH, by vitamin B-12-specific binding protein, immobilized to a solid phase of polymeric microspheres. Detection involves monitoring the activity of the tracer enzyme (alkaline phosphatase) coupled to a derivative of cyanocobalamin. Total assay precision is 7.9% for vitamin B-12 at 200 ng/L, 6.6% at 400 ng/L, and 6.7% at 800 ng/L. Assay sensitivity, calculated as 2 SD from the zero calibrator, is 37 (+/- 9) ng/L. The dynamic range extends to 2000 ng/L. Analytical recovery of 300 and 600 ng/L additions of vitamin B-12 to sera with basal concentrations of 30-400 ng/L was 102.5%. Results of the assay correlated well with those of commercially available radioisotope assays. No interference was observed in specimens from patients with pernicious anemia, chronic or acute myelogenous leukemia, or renal failure. Cross-reactivity with cobinamide (1 g/L) was < 0.00003%. Vitamin B-12 measurements for blood specimens drawn into serum, EDTA, or heparinized plasma-collection tubes agreed within 3%.

Topics: Anemia, Pernicious; Animals; Autoanalysis; Humans; Hydrogen-Ion Concentration; Intrinsic Factor; Kidney Diseases; Leukemia, Myeloid, Acute; Quality Control; Swine; Vitamin B 12

The effects of methotrexate (inhibiting dihydrofolate reductase) and nitrous oxide (inactivating methionine synthase) on intracellular folate coenzyme levels of leukemic cells were studied. Blast cells from 10 cases of acute myeloid leukemia (AML) and 5 cases of acute lymphoid leukemia (ALL) were incubated with 5 x 10(-8) M [3H] 5-formyltetrahydrofolate (5-formylTHF) for 18 h to label intracellular folate pools, which were subsequently quantitated by high performance liquid chromatography (HPLC). In AML, 5-methylTHF made up 53% of the total folate pool followed by 10-formylTHF (26%), 5-formylTHF (10%), THF (9%) and DHF (1%). Cells from ALL differed from AML (p less than 0.05) with respect to 10-formylTHF (17%) and DHF (10%). Exposure to nitrous oxide (8 h) caused an equal decrease of 10-formylTHF and 5-formylTHF in both AML (30%) and ALL (45%), whereas 5-methylTHF increased (130%). Methotrexate (4 h, 10(-6) M) caused an accumulation of DHF and a decrease of 5-methylTHF in both AML (32%) and ALL (12%). A specific reduction of the 10-formylTHF (50%) and 5-formylTHF (25%) pools was noticed in ALL. Exposure to nitrous oxide prior to methotrexate treatment aggravated the reduction of 10-formylTHF and 5-formylTHF presumably by impaired replenishment from the 5-methylTHF pool. In conclusion, this study demonstrates a significant difference in folate coenzyme distribution between cells from AML and ALL. Moreover it is shown that nitrous oxide and methotrexate treatment of leukemic cells cause an accumulation of 5-methylTHF and DHF respectively at the expense of other folate forms. The presence of substantial amounts of DHF in cells from ALL together with the specific reduction of 10-formylTHF (necessary for purine synthesis) during MTX treatment may in part explain the efficacy of methotrexate in the treatment of ALL.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Enzyme Activation; Folic Acid; Folic Acid Antagonists; Humans; Leukemia, Myeloid, Acute; Methotrexate; Nitrous Oxide; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Tumor Cells, Cultured; Vitamin B 12

The uptake of serum-bound 57Co-cyanocobalamin by uninduced and dimethylsulphoxide-induced HL60 cells has been studied. The data indicate that during the maturation of promyelocytes to neutrophil granulocytes, there is a progressive and marked reduction in (a) the number of surface receptors for the transcobalamin II-cobalamin complex (TCII-Cbl) per cell up to the metamyelocyte stage and (b) the amount of TCII-Cbl entering a cell, through the entire maturation pathway. The maturation of promyelocytes to neutrophil granulocytes was also accompanied by a marked reduction in intracellular vitamin B12 content. These observations help in explaining some features of granulocytopoiesis in cobalamin deficiency.

Topics: Biological Transport; Cell Differentiation; Cell Line; Cobalt Radioisotopes; Dimethyl Sulfoxide; Humans; Kinetics; Leukemia, Myeloid, Acute; Neutrophils; Temperature; Vitamin B 12

The ability of nitrous oxide to inhibit the in vivo growth of hematological neoplasms was investigated in a rat model for acute myeloid leukemia (BNML). Nitrous oxide, administered in a concentration of 67% with 33% oxygen, resulted in a reduction of spleen and liver weights of approx. 30%, as compared with leukemic rats kept in ambient air. Peripheral white cell counts were also considerably lower in the treated rats. Plasma levels of vitamin B12 were found to be elevated in untreated leukemia, but fell to about normal levels after nitrous oxide exposure. On the contrary, folic acid levels were low in untreated leukemic rats, and significantly higher in animals exposed to nitrous oxide. The observed effects of nitrous oxide appeared to be dose-dependent. The deoxyuridine suppression test performed with leukemic cells became abnormal after nitrous oxide inhalation, in accordance with the effect on normal bone marrow. These results indicate that the interference of nitrous oxide with vitamin B12-related metabolism, which leads to impairment of de novo thymidine synthesis, has the potency to reduce leukemic proliferation in vivo.

Topics: Animals; Cell Division; Folic Acid; Kinetics; Leukemia, Experimental; Leukemia, Myeloid, Acute; Leukocyte Count; Male; Nitrous Oxide; Organ Size; Rats; Vitamin B 12

A patient is described who appeared to demonstrate modulation of acute myelogenous leukaemia with vitamin B12 deprivation. Support for this observation was obtained via an in vitro bone marrow blast cell assay. The addition of B12 to this patient's bone marrow in vitro significantly stimulated the colony forming ability of the blast cells. Patients with B12 deficiency have an increased incidence of haematopoietic malignancies and excessive replacement of B12 may in some cases have the potential of accelerating such disorders. Intensive B12 replacement in refractory megaloblastic anaemias should be done with caution.

Topics: Aged; Bone Marrow; Cell Count; Female; Humans; Leukemia, Myeloid, Acute; Tumor Stem Cell Assay; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adult; Aged; Cells, Cultured; Cyclic AMP; Cyclic GMP; Folic Acid; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Lymphocytes; Middle Aged; Prostaglandins E; Sialic Acids; Vitamin B 12

Topics: Adult; Anemia, Macrocytic; Anemia, Megaloblastic; Humans; Leukemia, Myeloid, Acute; Male; Vitamin B 12

The unsaturated B12 binding capacity (UBBC) of the serum and the binding capacity of each of the 3 vitamin B12 binders--the transcobalamins (TC) I, II and III were determined in 21 patients with polycythaemia vera (PV) during the course of the disease and following treatment, using the recently described charged cellulose filter technique. High serum UBBC due to elevated serum TCIII was found in all patients. TCI was moderately elevated in patients who had leucocytosis with a shift to the left. The changes in serum TCIII and UBBC correlated with the activity of the disease. Chemotherapy resulted in a decrease in TCIII and UBBC. The decrease in TCIII and UBBC folowing chemotherapy may be observed before a decrease in the haematocrit and the leucocyte count occurs. Activation of the disease may be assessed by the elevation of TCIII and UBBC. The onset of acute myeloblastic crisis in 1 patient was associated with a decrease in TCIII and TCI levels and a rise in serum TCII. The determination of TCIII and UBBC may be helpful in differentiating true from secondary polycythaemia.

Topics: Blood Proteins; Busulfan; Humans; Leukemia, Myeloid, Acute; Melphalan; Polycythemia Vera; Protein Binding; Transcobalamins; Vitamin B 12

Topics: DNA, Neoplasm; Erythrocytes; Erythropoiesis; Esterases; Humans; Iron; Leukemia, Myeloid, Acute; Staining and Labeling; Vitamin B 12

Topics: Biological Assay; Blood Proteins; Chromatography; Cobalt Radioisotopes; Humans; In Vitro Techniques; Kinetics; Leucine; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocytes; Protein Binding; Tritium; Vitamin B 12

Topics: Adolescent; Blood Transfusion; Cytosine; Female; Folic Acid; Humans; Leukemia, Erythroblastic, Acute; Leukemia, Myeloid, Acute; Syndrome; Vincristine; Vitamin B 12

Topics: Humans; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Methods; Vitamin B 12

Topics: Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Vitamin B 12

Topics: Adult; Aged; Erythrocytes; Folic Acid; Histiocytes; Hodgkin Disease; Humans; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Lymphoma, Large B-Cell, Diffuse; Middle Aged; Vitamin B 12

Topics: Acute Disease; Adolescent; Adult; Afibrinogenemia; Autopsy; Biopsy; Blood Proteins; Bone Marrow; Child; Disseminated Intravascular Coagulation; Female; Hemorrhage; Humans; Leukemia, Myeloid, Acute; Leukopenia; Liver; Male; Middle Aged; 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: Adult; Agranulocytosis; Alpha-Globulins; Beta-Globulins; Blood Cell Count; Blood Protein Electrophoresis; Bone Marrow Examination; Cobalt Isotopes; Cytarabine; Humans; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Muramidase; Periodicity; Protein Binding; Vitamin B 12

Topics: Anemia, Pernicious; Animals; Bone Marrow; Bone Marrow Cells; Carbon Isotopes; Coenzymes; DNA Replication; Female; Friend murine leukemia virus; Leukemia, Experimental; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocytes; Mice; Nucleosides; Oxidoreductases; Ribonucleotides; Spleen; Vitamin B 12

Topics: Aged; Anemia, Hypochromic; Anemia, Sideroblastic; Blood Platelets; Bone Marrow Cells; Erythrocyte Count; Female; Folic Acid; Hemoglobinometry; Humans; Iron; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocyte Count; Male; Middle Aged; Multiple Myeloma; Reticulocytes; Vitamin B 12

Topics: Antineoplastic Agents; Busulfan; Chromatography, Gel; Cobalt Isotopes; Female; Humans; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Male; Middle Aged; Protein Binding; Vitamin B 12

Topics: Anabolic Agents; Anemia, Sideroblastic; Erythrocytes, Abnormal; Folic Acid; Humans; Iron; Leukemia, Myeloid, Acute; Liver Cirrhosis; Pyridoxine; Terminology as Topic; Transferrin; Vitamin B 12

Topics: Acute Disease; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Prognosis; Vitamin B 12

Topics: Aged; Anemia, Pernicious; Cerebral Hemorrhage; Humans; Iron; Leukemia, Myeloid, Acute; Male; Thrombocytopenia; Vitamin B 12

Topics: Adult; Buffers; Child; Edetic Acid; Formaldehyde; Humans; Imidazoles; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocytes; Methionine; Sulfur Isotopes; Vitamin B 12