phosphorus-radioisotopes and Leukemia--Myeloid

Topics: Anemia; Apoptosis; Clone Cells; Disease Progression; Erythropoiesis; Erythropoietin; Female; Growth Substances; Hematologic Tests; Hematopoietic Stem Cells; Humans; Iron; Leukemia, Myeloid; Male; Myeloproliferative Disorders; Phlebotomy; Phosphorus Radioisotopes; Polycythemia Vera; Pregnancy; Pregnancy Complications, Hematologic; Receptors, Erythropoietin; Receptors, Growth Factor; Thrombocytosis; Thrombosis

The clinical course in both polycythaemia vera (PV) and essential thrombocythaemia (ET) is characterized by significant thrombohaemorrhagic complications and variable risk of disease transformation into myeloid metaplasia with myelofibrosis or acute myeloid leukaemia. Randomized studies have shown that the risk of thrombosis was significantly reduced in ET with the use of hydroxyurea (HU) and in PV with the use of chlorambucil or 32P. However, the use of chlorambucil or 32P has been associated with an increased risk of leukaemic transformation. Subsequently, other studies have suggested that both HU and pipobroman may be less leukaemogenic and as effective as chlorambucil and 32P for preventing thrombosis in PV. However, the results from these prospective studies have raised concern that even HU and pipobroman may be associated with excess leukaemic events in both ET and PV. The recent introduction of anagrelide as a specific platelet-lowering agent, the demonstration of treatment efficacy with interferon-alpha, and the revived interest in using low-dose acetylsalicylic acid provide the opportunity to initiate prospective randomized studies incorporating these treatments.

Topics: Adult; Aged; Aspirin; Chlorambucil; Disease Progression; Female; Hemorrhage; Humans; Hydroxyurea; Interferon-alpha; Leukemia, Myeloid; Leukemia, Radiation-Induced; Male; Middle Aged; Phlebotomy; Phosphorus Radioisotopes; Pipobroman; Polycythemia Vera; Primary Myelofibrosis; Prospective Studies; Quinazolines; Thrombocythemia, Essential; Thrombosis

Topics: Acute Disease; Alkylating Agents; Busulfan; Chlorambucil; Humans; Hydroxyurea; Leukemia, Myeloid; Leukemia, Radiation-Induced; Phlebotomy; Phosphorus Radioisotopes; Pipobroman; Platelet Aggregation Inhibitors; Polycythemia Vera; Randomized Controlled Trials as Topic; Survival Rate

An analysis of the risk of progression towards leukemia, carcinoma and myelofibrosis was performed in 93 patients treated by 32P alone (PVSG protocols) since 1970-1979, 395 patients over the age of 65 years treated by 32P with or without maintenance therapy using hydroxyurea (French protocol) since 1980-1994, and 202 patients under the age of 65 treated by either hydroxyurea or pipobroman since 1980. The risk of leukemia, or myelodysplasia, or lymphoma in the 32P-treated patients was 10% at the 10th year, but increase after that time to reach a value of about 30% at the 20th year, in the surviving case. This risk was not dose-related. Despite a marked reduction of the cumulative 32P dose in the patients maintained by hydroxyurea, the actuarial risk was 19% at the 10th year. In the patients treated exclusively by non radio-mimetic agents (hydroxyurea or pipobroman) a risk of 10% at the 10th year was observed. The risk of carcinoma (excluding skin cancers) was about 15% at the 10th year in the 32P-treated cases, a value similar to that generally reported by the French statistics. There was no prevalence of digestive carcinomas. In contrast, the patients receiving 32P and hydroxyurea as maintenance had an excess risk: 29% at the 10th year. In the relatively young cases treated by non radio-mimetic agents, the risk was similar in both arms: 9% at the 10th year, similar to the expected incidence at this age. The risk of myelofibrosis with myeloid metaplasia was still relatively low at the 10th year, about 15% in all arms, but increased towards a value higher than 30% in the patients surviving at the 20th year. At the present time, but in only a few cases with long-term following, no myelo-fibrosis with splenic metaplasia has been observed in the pipobroman-treated cases. The present results, which need to be confirmed (the present analysis has been done in spring 95) suggest that:-the use of non radio-mimetic agents does not protect against leukemic transformation, which may be a consequence of the disease; rather than of the treatment,-maintenance therapy after initial use of 32P increases the risk of both leukemia and carcinoma,-and hydroxyurea does not delay the risk of developing myelo-fibrosis, in comparison with 32P alone.

Topics: Actuarial Analysis; Acute Disease; Carcinoma; Cause of Death; Disease Progression; Follow-Up Studies; Humans; Hydroxyurea; Incidence; Leukemia, Myeloid; Leukemia, Radiation-Induced; Lymphoma; Neoplasms, Radiation-Induced; Phlebotomy; Phosphorus Radioisotopes; Pipobroman; Polycythemia Vera; Prevalence; Primary Myelofibrosis; Risk; Splenomegaly

Topics: Animals; Bone Marrow; Bone Marrow Cells; Cell Survival; Dogs; Granulocytes; Half-Life; Hematopoiesis; Humans; In Vitro Techniques; Injections, Intramuscular; Injections, Intravenous; Isoflurophate; Kinetics; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocytes; Methods; Neutropenia; Neutrophils; Phosphorus Radioisotopes; Remission, Spontaneous; Time Factors

Topics: Bone Marrow; Busulfan; Diagnosis, Differential; Erythropoiesis; Granulocytes; Humans; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Osteosclerosis; Phosphorus Radioisotopes; Polycythemia; Polycythemia Vera; Primary Myelofibrosis; Thrombocythemia, Essential

Topics: Anemia, Aplastic; Animals; Bacteriological Techniques; Bone Marrow; Glomerular Filtration Rate; Histological Techniques; Humans; Hypersplenism; Immunologic Techniques; Iodine Radioisotopes; Kidney; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Muramidase; Neutrophils; Phosphorus Radioisotopes; Polycythemia Vera; Rabbits

An analysis of the risk of progression towards leukemia, carcinoma and myelofibrosis was performed in 93 patients treated by 32P alone (PVSG protocols) since 1970-1979, 395 patients over the age of 65 years treated by 32P with or without maintenance therapy using hydroxyurea (French protocol) since 1980-1994, and 202 patients under the age of 65 treated by either hydroxyurea or pipobroman since 1980. The risk of leukemia, or myelodysplasia, or lymphoma in the 32P-treated patients was 10% at the 10th year, but increase after that time to reach a value of about 30% at the 20th year, in the surviving case. This risk was not dose-related. Despite a marked reduction of the cumulative 32P dose in the patients maintained by hydroxyurea, the actuarial risk was 19% at the 10th year. In the patients treated exclusively by non radio-mimetic agents (hydroxyurea or pipobroman) a risk of 10% at the 10th year was observed. The risk of carcinoma (excluding skin cancers) was about 15% at the 10th year in the 32P-treated cases, a value similar to that generally reported by the French statistics. There was no prevalence of digestive carcinomas. In contrast, the patients receiving 32P and hydroxyurea as maintenance had an excess risk: 29% at the 10th year. In the relatively young cases treated by non radio-mimetic agents, the risk was similar in both arms: 9% at the 10th year, similar to the expected incidence at this age. The risk of myelofibrosis with myeloid metaplasia was still relatively low at the 10th year, about 15% in all arms, but increased towards a value higher than 30% in the patients surviving at the 20th year. At the present time, but in only a few cases with long-term following, no myelo-fibrosis with splenic metaplasia has been observed in the pipobroman-treated cases. The present results, which need to be confirmed (the present analysis has been done in spring 95) suggest that:-the use of non radio-mimetic agents does not protect against leukemic transformation, which may be a consequence of the disease; rather than of the treatment,-maintenance therapy after initial use of 32P increases the risk of both leukemia and carcinoma,-and hydroxyurea does not delay the risk of developing myelo-fibrosis, in comparison with 32P alone.

Topics: Actuarial Analysis; Acute Disease; Carcinoma; Cause of Death; Disease Progression; Follow-Up Studies; Humans; Hydroxyurea; Incidence; Leukemia, Myeloid; Leukemia, Radiation-Induced; Lymphoma; Neoplasms, Radiation-Induced; Phlebotomy; Phosphorus Radioisotopes; Pipobroman; Polycythemia Vera; Prevalence; Primary Myelofibrosis; Risk; Splenomegaly

Blastic transformation of essential thrombocythemia (ET) preceded by chemotherapy is occasionally described in the literature. In ET as well as in other myeloproliferative disorders the leukemogenic effect of alkylating agents and (32)P is well established, and recent reports also indicate a certain leukemogenic effect of hydroxyurea in these disorders. However, leukemic transformation in untreated ET seems to be a rare event. This is probably due to the fact that, at some time during their clinical course, most ET patients receive chemotherapy and are thereby exposed to leukemogenic challenge. We report on a woman with ET who had not received cytoreductive treatment prior to the development of acute myeloid leukemia, indicating that this transformation was a natural progression of her disorder.

Topics: Acute Disease; Aged; Alkylating Agents; Female; Humans; Leukemia, Myeloid; Lymphocyte Activation; Phosphorus Radioisotopes; Thrombocythemia, Essential

The cAMP analogue 8-bromo-cAMP (8BrcAMP) inhibits granulocyte-colony-stimulating factor (G-CSF)-stimulated DNA synthesis in myeloid NFS-60 cells. We examined the effect of 8BrcAMP addition on the G-CSF-stimulated extracellular signal-related protein kinase 1 (Erk-1), p21ras and Raf-1 activation. The Erk-1 activity was not down-regulated by the increase in intracellular cAMP levels, whereas p21ras and Raf-1 activities were, suggesting that Erk-1 activity might not be dependent on upstream p21ras and/or Raf-1 activity in this system. To explore this possibility further, we sought to determine whether there were downstream substrates of Raf-1 that were distinguishable from those of Erk-1 by using two-dimensional SDS/PAGE analysis of the protein phosphorylation patterns of NFS-60 cell cytosolic extracts treated with exogenous Raf-1 or Erk-1 in the presence of [gamma-32P]ATP. The two phosphorylation patterns were found to have many differences. To gain further insights into the possible relevance of these phosphorylation patterns and as an approach to exploring in more detail the inhibitory effect of 8BrcAMP, two-dimensional SDS/PAGE analysis was performed on the cytosolic extracts of 32P-labelled NFS-60 cells treated with G-CSF, in the absence or presence of 8BrcAMP. It was found that the phosphorylated proteins whose appearance was specific to the action of exogenous Raf-1 were sensitive to the action of 8BrcAMP in vivo, whereas those whose appearance was specific to the action of exogenous Erk-1 alone, or common to the actions of Raf-1 and Erk-1, were 8BrcAMP-insensitive. The results are consistent with a Raf-1-independent pathway for Erk-1 activation in G-CSF treated myeloid cells, and a number of potential downstream substrates of these kinases have been identified for further characterization.

Topics: 8-Bromo Cyclic Adenosine Monophosphate; Animals; Calcium-Calmodulin-Dependent Protein Kinases; Cell-Free System; DNA; Electrophoresis, Gel, Two-Dimensional; Granulocyte Colony-Stimulating Factor; Growth Inhibitors; Leukemia, Myeloid; Mice; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases; Phosphorus Radioisotopes; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-raf; Proto-Oncogene Proteins p21(ras); Substrate Specificity; Tumor Cells, Cultured

Reactive metabolites of benzene (BZ) play important roles in BZ-induced hematotoxicity. Although reactive metabolites of BZ covalently bind to DNA, the significance of DNA adduct formation in the mechanism of BZ toxicity is not clear. These studies investigated the covalent binding of the BZ metabolites hydroquinone(HQ) and 1,2,4-benzenetriol(BT) using the DNA [32P]postlabeling method and explored the potential relationship between DNA adduct formation and cell differentiation in human promyelocytic leukemia (HL-60) cells, a model system for studying hematopoiesis. Maturation of HL-60 cells to granulocytes, as assessed by light and electron microscopy, was significantly inhibited in cells that were pretreated with HQ or BT prior to inducing differentiation with retinoic acid (RA). The capacity of RA-induced cells to phagocytose sheep red blood cells (RBC) and to reduce nitroblue tetrazolium (NBT), two functional parameters characteristic of mature, differentiated neutrophils, was also inhibited in cells pretreated with HQ or BT. These BZ metabolite treatments induced DNA adduct formation in HQ- but not in BT-treated cells. These results indicate that whereas HQ and BT each block granulocytic differentiation in HL-60 cells, DNA adducts were observed only following HQ treatment. Thus DNA adduct formation may be important in HQ but not in BT toxicity.

Topics: Benzene Derivatives; Cell Death; Cell Differentiation; Cell Division; DNA; DNA Adducts; Granulocytes; HL-60 Cells; Humans; Hydroquinones; Leukemia, Myeloid; Mutagens; Phosphorus Radioisotopes; Tretinoin

The proliferation and development of hematopoietic cells occurs in close association with bone marrow stroma. Heparan sulfate is a major component of the stroma. We have isolated a form of heparan sulfate proteoglycan from a human stromal cell line grown in vitro in the presence of [35S]sulfate. This proteoglycan contains a phosphatidylinositol component which likely anchors it to the stromal cell membrane. The glycosaminoglycan chains of this proteoglycan could induce maturation of the HL-60 myeloid leukemia cell line. A less hydrophobic heparan sulfate proteoglycan was also present in the stroma, but could not induce HL-60 maturation. The two heparan sulfates had glycosaminoglycan chains that were similar in size (36 Kd) and charge density. Structural studies suggested only minor but perhaps significant differences in the carbohydrate sequences of the two heparan sulfates. The relationship of these subtle structural differences to the difference observed in differentiation-inducing activity remains to be elucidated.

Topics: Bone Marrow Cells; Cell Differentiation; Glycosylphosphatidylinositols; Heparan Sulfate Proteoglycans; HL-60 Cells; Humans; Leukemia, Myeloid; Molecular Structure; Molecular Weight; Phosphatidylinositols; Phosphorus Radioisotopes; Stromal Cells; Sulfates

There exists circumstantial evidence for activation of phospholipase D (PLD) in intact cells. However, because of the complexity of phospholipid remodeling processes, it is essential to distinguish PLD clearly from other phospholipases and phospholipid remodeling enzymes. Therefore, to establish unequivocally PLD activity in dimethyl sulfoxide-differentiated HL-60 granulocytes, to demonstrate the relative contribution of PLD to phospholipid turnover, and to validate the hypothesis that the formation of phosphatidylethanol is an expression of PLD-catalyzed transphosphatidylation, we have developed methodologies to label HL-60 granulocytes in 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine (alkyl-PC) with 32P without labeling cellular ATP. These methodologies involve (a) synthesis of alkyl-lysoPC containing 32P by a combination of enzymatic and chemical procedures and (b) incubation of HL-60 granulocytes with this alkyl-[32P] lysoPC which enters the cell and becomes acylated into membrane-associated alkyl-[32P]PC. Upon stimulation of these 32P-labeled cells with the chemotactic peptide, N-formyl-Met-Leu-Phe (fMLP), alkyl-[32P]phosphatidic acid (alkyl-[32P]PA) is formed rapidly. Because, under these conditions, cellular ATP has not been labeled with 32P, alkyl-[32P]PA must be formed via PLD-catalyzed hydrolysis of alkyl-[32P]PC at the terminal phosphodiester bond. This result conclusively demonstrates fMLP-induced activation of PLD in HL-60 granulocytes. These 32P-labeled HL-60 granulocytes have also been stimulated in the presence of ethanol to produce alkyl-[32P]phosphatidylethanol (alkyl-[32P]PEt). Formation of alkyl-[32P]PEt parallels that of alkyl-[32P]PA with respect to time course, fMLP concentration, inhibition by a specific fMLP antagonist (t-butoxycarbonyl-Met-Leu-Phe), and Ca2+ concentration. These results strongly support the hypothesis that in HL-60 granulocytes, PEt is formed via PLD-catalyzed transphosphatidylation. Moreover, using HL-60 granulocytes double-labeled by incubation with [3H]alkyl-lysoPC and alkyl-[32P]lysoPC, it has been established that the early (30 s) appearance of alkyl-PA is due primarily to PLD, not phospholipase C as previously thought, and that alkyl-PEt is formed exclusively by PLD. These results constitute the first direct evidence for receptor-linked activation of PLD, leading to the generation of PA and PEt in an intact cell system.

Topics: Adenosine Triphosphate; Calcium; Enzyme Activation; Ethanol; Granulocytes; Humans; Kinetics; Leukemia, Myeloid; N-Formylmethionine Leucyl-Phenylalanine; Phosphatidic Acids; Phosphatidylethanolamines; Phospholipase D; Phospholipases; Phospholipids; Phosphorus Radioisotopes; Platelet Activating Factor; Tumor Cells, Cultured; Type C Phospholipases

We have characterized the phosphorylation of "abp38" before and after the differentiation of mouse myeloid leukemic cells (M1 cells). The abp38 of both undifferentiated and differentiated M1 cells contained phosphoserine and phosphotyrosine. The extent of phosphorylation of abp38 decreased to about 30% of the value of undifferentiated cells during cell differentiation; phosphoserine and phosphotyrosine decreased to 41 and 11% of the values before differentiation, respectively.

Topics: Actins; Amino Acids; Animals; Cell Differentiation; Cells, Cultured; Cytoskeletal Proteins; Immunoelectrophoresis; Leukemia, Myeloid; Mice; Neoplasm Proteins; Phosphorus Radioisotopes; Phosphorylation; Precipitin Tests

Antibodies against phosphotyrosine are a powerful tool with which to identify proteins phosphorylated on tyrosine residues, such as viral oncogene-encoded transforming proteins and their cellular protein substrates. Probed on human leukemia cell lines, phosphotyrosine antibodies recognized a 210,000-molecular-weight protein (p210) in K562 cells, a cell line derived from a Philadelphia (Ph)'-positive chronic myelogenous leukemia (CML), but recognized no protein in control Ph'-negative non-CML leukemia cells. The p210 protein was also recognized by antisera against v-abl-encoded polypeptides and displayed kinase activity, phosphorylating itself on tyrosine, in an immunocomplex kinase assay. These data are consistent with reported findings of the expression of a recombined bcr-abl gene in Ph'-positive CML cells, leading to the synthesis of an altered p210c-abl protein endowed with tyrosine kinase activity. Phosphotyrosine antibodies also detected the expression of the p210c-abl protein in fresh bone marrow cells harvested from CML patients in blast crisis. Besides the p210c-abl protein kinase, phosphotyrosine antibodies recognized other proteins with molecular weights of 110,000, 68,000, and 36,000 (p110, p68, and p36) in K562 cells. When [gamma-32P]ATP was added to nonionic detergent-extracted cells, these proteins became phosphorylated on tyrosine, as confirmed by phosphoamino acid analysis. A comparison with fibroblasts transformed by the v-abl, v-src, and v-fps oncogenes suggested the identity of the p36 protein with the common 36-kilodalton protein substrate of viral oncogene-encoded tyrosine kinases. Enhanced tyrosine phosphorylation of cellular proteins is thus a feature shared by cells transformed by v-abl and cells expressing a rearranged bcr-abl gene.

Topics: Amino Acids; Antibodies; Antigen-Antibody Complex; Bone Marrow; Cell Line; Fusion Proteins, bcr-abl; Humans; Leukemia, Myeloid; Neoplasm Proteins; Phosphorus Radioisotopes; Phosphotyrosine; Protein-Tyrosine Kinases; Recombinant Fusion Proteins; Recombinant Proteins; Reference Values; Tyrosine

Bleomycin causes lesions to DNA in intact cells and in purified DNA under appropriate conditions. Using a middle repetitive DNA sequence called alpha-DNA as a target sequence, we have compared the sequence specificity of bleomycin-induced DNA cleavage in intact human cells and in purified human DNA. Bleomycin induces numerous cleavage sites in alpha-DNA which vary widely in intensity and give rise to a complex pattern of bands on a DNA sequencing gel. Unexpectedly, the intensity and position of bleomycin-induced DNA cleavage sites are very similar in intact human cells and in purified human DNA.

Topics: Base Sequence; Bleomycin; Cell Line; DNA, Neoplasm; Humans; Leukemia, Myeloid; Phosphorus Radioisotopes

The activity of P-32 removed during leukapheresis of a patient previously administered P-32 for therapy of chronic myelogenous leukemia (CML) was determined. The bremsstrahlung produced by P-32 beta rays in the pheresis bags allowed the quantitation of radioactivity by well counting in a sodium iodide detector and by a gamma camera. Bremsstrahlung counting demonstrated that leukapheresis removes such a small amount of radioactivity that the therapeutic effect of a previously administered P-32 dose was still valid. Bremsstrahlung counting offers advantages to a Nuclear Medicine Department over the conventional use of a liquid scintillation counter to detect P-32 beta rays in that it is simpler and more readily available.

Topics: Humans; Leukapheresis; Leukemia, Myeloid; Male; Phosphorus Radioisotopes; Radiotherapy Dosage; Scintillation Counting

Topics: Animals; Autoradiography; Carbon Radioisotopes; Cell Extracts; Cell Line; Cold Temperature; Electrophoresis; Isoelectric Focusing; Leukemia, Myeloid; Mice; Phosphoproteins; Phosphorus Radioisotopes; Sulfur Radioisotopes; Tissue Extracts

Determining granulocyte kinetics with DF32P allows various parameters to be gained during the in-vitro marking, such as the total blood granulocyte pool, circulating granulocyte pool, marginal granulocyte pool, daily granulocyte exchange rate and half decay period of granulocytes. The half decay period of granulocytes, bone-marrow reserve in myelocytes, metamyelocytes and band cells as well as polymorphonuclear neutrophils can be determined by in-vitro marking, with DF32P being intravenously injected. The combination of both procedures with DF32P will reveal the half decay period, pool sizes and exchange rates of the proliferating myelocyte compartiment in bone-marrow and mature blood granulocytes. If 51Cr is used for determining granulocyte kinetics the surface activities of various organs, such as heart, liver, spleen, and lungs, can mainly be determined in addition to the half-life of leucocytes, indicating the degradation or storage of cells in certain areas of the body. In addition to normal values those findings are principally presented which were obtained with in-vitro marking by DF32P and 51Cr in chronic myeloid leukaemia, osteomyelofibrosis or osteomyelosclerosis respectively and in hypersplenism.

Topics: Cell Survival; Chromium Radioisotopes; Granulocytes; Half-Life; Humans; Hypersplenism; Isoflurophate; Leukemia, Myeloid; Leukocyte Count; Phosphorus Radioisotopes; Primary Myelofibrosis

Topics: Blood; Child; Extracorporeal Circulation; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Phosphorus Radioisotopes; Spleen; Thymus Gland

Topics: Aged; Female; Humans; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Radiation-Induced; Male; Middle Aged; Phosphorus Radioisotopes; Polycythemia Vera

Chronic granulocytic leukemia developed in a 59-year-old woman who had previously received a total of 21 mCi -32P for polycythemia vera. She was treated with Myleran (busulphan) for her chronic granulocytic leukemia. Cytogenic studied revealed deletion of chromosomes No. 8 and 12, and translocation between 1 and 8. The patient also developed a severe antoimmune hemolytic anemia, for which she received prednisone treatment. She died with a perforated stomach ulcer.

Topics: Anemia, Hemolytic, Autoimmune; Busulfan; Chromosomes, Human, 1-3; Chromosomes, Human, 6-12 and X; Chronic Disease; Female; Humans; Karyotyping; Leukemia, Myeloid; Middle Aged; Phosphorus Radioisotopes; Polycythemia Vera; Prednisone; Translocation, Genetic

Topics: Aged; Cyclophosphamide; Hodgkin Disease; Humans; Intestinal Absorption; Leukemia, Lymphoid; Leukemia, Myeloid; Middle Aged; Multiple Myeloma; Phosphates; Phosphorus Radioisotopes

Results are presented of chromosome studies of bone marrow cells from a 62-year-old woman. The patient had been given 40 ml of Thorotrast in connection with a neuro-radiological examination 34 years earlier. Clinically, the patient was now considered to be in an incipient myeloid leucaemic phase. Ninety-seven per cent of the bone marrow cells belonged to a clone with characteristic marker chromosomes induced by radiation. Few data are available on chromosome analysis of bone marrow cells from Thorotrast patients. Therefore, the results of the present study are compared with data from chromosome analyses of 32P-treated patients with polycythaemia vera, in whom large clones were found in the bone marrow. The results of chromosome analysis of bone marrow cells from the Thorotrast patient support previous hypotheses concerning the carcinogenesis in radiation-induced leucaemia in patients with polycythaemia vera, treated with 32P. In the latter patients, the clone cells are pressumed to represent cell populations with selective qualities, originating from radiation-damaged cells, which possibly possess an increased tendency to malignant transformation because of a more pronounced sensitivity to carcinogenic agents. The cells might also be potentially malignant and manifest themselves as leucaemic cells, if the patient's immunological defence mechanism is broken.

Topics: Bone Marrow; Bone Marrow Cells; Chromosome Aberrations; Chromosome Inversion; Chromosomes, Human, 1-3; Clone Cells; Female; Humans; Karyotyping; Leukemia, Myeloid; Leukemia, Radiation-Induced; Middle Aged; Phosphorus Radioisotopes; Radiation Effects; Thorium Dioxide

Polycythemia rubra vera and chronic myelogenous leukemia are both myeloproliferative disorders and, as such, share certain clinical features. Although some myeloproliferative disorders may transform into others, conversion of polycythemia rubra vera to chronic myelogenous leukemia has been denied. We report here an elderly man with polycythemia rubra vera and a normal leukocyte alkaline phosphatase who developed chronic myelogenous leukemia with a low leukocyte alkaline phosphatase and a marrow karyotype of 45, X, Ph1-positive. In addition, we have collected evidence of two similar cases and thus conclude that, although uncommon, polycythemia rubra vera may on occasion progress to chronic myelogenous leukemia.

Topics: Adult; Aged; Chromosome Aberrations; Chromosomes, Human, 21-22 and Y; Female; Humans; Karyotyping; Leukemia, Myeloid; Male; Middle Aged; Neoplasms, Radiation-Induced; Phosphorus Radioisotopes; Polycythemia Vera

A review is presented of the clinical, physiopathological and therapeutic aspects of four varieties of chronic myeloproliferative syndrome: polycythemia vera, idiopathic thrombocythemia, chronic myelocytic leukemia and idiopathic myeloid metaplasia. Routine and experimental therapeutic approaches are discussed.

Topics: Aged; Bloodletting; Busulfan; Chlorambucil; Female; Humans; Leukemia, Myeloid; Male; Myeloproliferative Disorders; Phosphorus Radioisotopes; Polycythemia Vera; Primary Myelofibrosis; Remission, Spontaneous; Thrombocytosis

Topics: Base Sequence; Burkitt Lymphoma; Cell Line; Cells, Cultured; Centrifugation, Density Gradient; Chromatography, DEAE-Cellulose; Genes; Humans; Lectins; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Lymphocyte Activation; Lymphocytes; Oligonucleotides; Pancreas; Phosphorus Radioisotopes; Purines; Remission, Spontaneous; Ribonucleases; RNA, Ribosomal

Topics: Busulfan; Female; Humans; Leukemia, Myeloid; Male; Patient Care Planning; Phosphorus Radioisotopes; Prognosis; Retrospective Studies; Spleen; Splenomegaly

Topics: Agranulocytosis; Cell Division; DNA Replication; Humans; Kinetics; Leukemia, Lymphoid; Leukemia, Myeloid; Neutrophils; Phosphorus Radioisotopes

Topics: Antineoplastic Agents; Busulfan; Humans; Hydroxyurea; Leukemia, Myeloid; Phosphorus Radioisotopes

Topics: Humans; Leukemia; Leukemia, Myeloid; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity; Radiotherapy; X-Ray Therapy

Topics: Chronic Disease; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Phosphorus; Phosphorus Radioisotopes; Radioactivity

Topics: Humans; Leukemia; Leukemia, Myeloid; Phosphorus; Phosphorus Radioisotopes; Polycythemia Vera; Radioactivity

Topics: Humans; Leukemia; Leukemia, Myeloid; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary

Topics: Blood Coagulation; Gold Radioisotopes; Humans; Leukemia; Leukemia, Myeloid; Phosphorus; Phosphorus Radioisotopes; Polycythemia Vera; Radioisotopes

Topics: Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Phosphorus; Phosphorus Radioisotopes

Topics: Humans; Leukemia; Leukemia, Myeloid; Phosphorus; Phosphorus Radioisotopes

Topics: Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary

Topics: Leukemia; Leukemia, Myeloid; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Polycythemia Vera; Radioactivity

Topics: Humans; Leukemia; Leukemia, Myeloid; Phosphorus; Phosphorus Radioisotopes