Effect of obesity on red cell mass results.
Measurement of red cell mass with isotope dilution remains an important diagnostic test in the evaluation of patients with suspected polycythemia vera (PCV). Results and reference ranges are typically expressed in units normalized for body weight (mL/kg). Obesity is common in polycythemic patients, and it is important to know how the various published normative ranges compare across a wide range of body weights. METHODS: We retrospectively reviewed 51 consecutive patients referred for red cell mass determination with 51Cr red blood cell dilution. Results were expressed in milliliters per kilogram (mL/kg) by using the actual patient weight and after adiposity adjustments using ideal body weight, body mass index (BMI) and combinations of height-weight, including body surface area. Results were classified as normal, elevated or PCV. RESULTS: There was a high prevalence of obesity in our population (28/51 [55%] with BMI > 27 kg/m2, BMI range 16.0-54.8 kg/m2). The method used to compensate for obesity had a dramatic effect on the derived red cell mass, the fraction of patients with elevated measurements and the fraction of patients meeting criteria for PCV. Concordance for categorization as normal, elevated or PCV by all methods was only 47.1%. CONCLUSION: Obesity is a common confounding factor in the interpretation of red cell mass measurements. Currently published reference ranges generate inconsistent results when extrapolated to obese patients. Further normative data on obese subjects are needed to determine which method (if any) is optimal. (+info)
Posttranslational processing of the thrombopoietin receptor is impaired in polycythemia vera.
Recently, we demonstrated a marked reduction in the expression of the thrombopoietin receptor, Mpl, in polycythemia vera (PV) platelets and megakaryocytes using an antiserum against the Mpl extracellular domain. To further examine this abnormality, we raised an antibody to the Mpl C-terminus. Immunologic analysis of PV platelets with this antiserum confirmed the reduction in Mpl expression. However, the C-terminal antiserum detected 2 forms of Mpl in PV platelets in contrast to normal platelets, in which a single form of Mpl was detected by both the extracellular domain and C-terminal antisera. Two-dimensional gel electrophoresis studies with isoelectric focusing in the first dimension identified normal platelet Mpl as an 85 to 92 kD protein with an isoelectric point (pI) of 5.5. PV platelets contained an additional 80 to 82 kD Mpl Mpl isoform with a pI of 6.5. Analysis of Mpl expressed by the human megakaryocytic cell line, Dami, showed 2 isoforms similar to those found in PV platelets suggesting a precursor-product relationship. Digestion of Dami cell and normal platelet lysates with neuraminidase converted the more acidic Mpl isoform to the more basic one, indicating that the 2 isoforms differed with respect to posttranslational glycosylation. Furthermore, in contrast to normal platelet Mpl, PV platelet Mpl was susceptible to endoglycosidase H digestion, indicating defective Mpl processing by PV megakaryocytes. The glycosylation defect was specific for Mpl, as 2 other platelet membrane glycoproteins, glycoprotein IIb and multimerin, were processed normally. Importantly, the extent of the PV platelet Mpl glycosylation defect correlated with disease duration and extramedullary hematopoiesis. (+info)
Nonrandom chromosomal abnormalities in hematologic disorders of man.
A nonrandom pattern of chromosomal abnormalities occurs in bone marrow cells obtained from patients with hematologic disorders who have an abnormal karyotype involving a C group chromosome. An additional number 8 chromosome is the most common abnormality, found in more than one-half of the patients studies. An additional number 9 chromosome and the loss of all or part of a number 7 are abnormalities that occur more often than might be expected by chance. It is proposed that specific human chromosomal abnormalities may be related to different specific etiologic agents. (+info)
Electron microscopic x-ray microanalysis of normal and leukemic human lymphocytes.
A comparative study of the elemental content of normal and leukemic cells was undertaken on a few subjects, using electron microscopic x-ray microanalysis. Phosphorus, sulfur, chlorine, calcium, copper, and zinc were detected in intracellular loci. The concentration of some of the above elements appeared to be disease related. In leukemic lymphocytes, the nuclear zinc was significantly lower than that recorded in normal lymphocytes, while the phosphorus was only moderately decreased. This suggests a faulty zinc uptake or binding in leukemic cells. The possible consequences of intracellular zinc deficiency are discussed. (+info)
Cloning of PRV-1, a novel member of the uPAR receptor superfamily, which is overexpressed in polycythemia rubra vera.
Polycythemia vera (PV) is a clonal stem cell disorder characterized by hyperproliferation of the erythroid, myeloid, and megakaryocytic lineages. Although it has been shown that progenitor cells of patients with PV are hypersensitive to several growth factors, the molecular pathogenesis of this disease remains unknown. To investigate the molecular defects underlying PV, we used subtractive hybridization to isolate complementary DNAs (cDNAs) differentially expressed in patients with PV versus normal controls. We isolated a novel gene, subsequently named PRV-1, which is highly expressed in granulocytes from patients with PV (n = 19), but not detectable in normal control granulocytes (n = 21). Moreover, PRV-1 is not expressed in mononuclear cells from patients with chronic myelogenous leukemia (n = 4) or acute myelogenous leukemia (n = 5) or in granulocytes from patients with essential thrombocythemia (n = 4) or secondary erythrocytosis (n = 4). Northern blot analysis showed that PRV-1 is highly expressed in normal human bone marrow and to a much lesser degree in fetal liver. It is not expressed in a variety of other tissues tested. Although PRV-1 is not expressed in resting granulocytes from normal controls, stimulation of these cells with granulocyte colony-stimulating factor induces PRV-1 expression. The PRV-1 cDNA encodes an open reading frame of 437 amino acids, which contains a signal peptide at the N-terminus and a hydrophobic segment at the C-terminus. In addition, PRV-1 contains 2 cysteine-rich domains homologous to those found in the uPAR/Ly6/CD59/snake toxin-receptor superfamily. We therefore propose that PRV-1 represents a novel hematopoietic receptor. (Blood. 2000;95:2569-2576) (+info)
Acute myelogenous leukaemia and myelomonocytic blast crisis following polycythemia vera in HIV positive patients: report of cases and review of the literature.
BACKGROUND: Acute myelogenous leukaemia (AML) and myeloproliferative diseases are rare in HIV-infected individuals and optimal treatment has not been defined. PATIENTS AND METHODS: We report on the cases of two HIV-infected men, one with AML and one with myeloid blast crisis after polycythaemia vera (PV). A comprehensive review of the available literature will be presented. RESULTS: Patient 1, a 57-year-old bisexual man known to be HIV seropositive for more than four years (CDC-category A1), presented with a pulmonary infiltrate. On admission WBC showed leukocytes 5.6 x 10(9)/l and the differential revealed 80% blasts. A diagnosis of AML FAB M0 was made. Pneumonia resolved under antibiotic treatment and the patient received induction chemotherapy. However, he once more developed multiple pulmonary infiltrates and died of respiratory failure despite broad spectrum antibiotic and antimycotic therapy. Autopsy revealed pulmonary aspergillosis. Patient 2 was a 63-year old HIV-positive hemophiliac (CDC A3) with a 10-year history of PV. On admission his white cell count showed leukocytes 256.6 x 10(9)/l with 82% blasts. Cytochemistry revealed myelomonocytic differentiation. The patient died of tumor lysis syndrome with renal and cardio-pulmonary failure two days later. CONCLUSIONS: This is the first report of an HIV-infected individual with AML M0. The literature describes the cases of 39 HIV+ patients with AML and only one further case with PV. The association of both, myeloproliferative disease and AML with HIV infection is coincidental. However, the proportion of FAB type M4/5 appears to be higher than in the general population. Despite a high risk of treatment associated mortality durable remissions can be achieved in a small proportion of HIV-infected patients with AML. (+info)
Tumor-like splenic extramedullary hematopoiesis in a patient with myelofibrosis.
A 61-year-old woman, who was diagnosed in 1982 as having polycythemia vera, was admitted to our hospital in July 1998 because of a splenic tumor in an enlarged spleen due to myelofibrosis. As it was difficult to identify the etiology of the splenic tumor, partial splenectomy was carried out. The resected tumor proved to be an extremely proliferative lesion as the result of extramedullary hematopoiesis. Since it is difficult to diagnose the etiology of splenic tumor, the collection and analysis of reports of relevant cases may well facilitate diagnosis. (+info)
Towards a molecular understanding of polycythemia rubra vera.
Polycythemia rubra vera (PV) is one of four diseases collectively called the myeloproliferative disorders (MPDs). Each disorder leads to an increased production of one or several hematopoietic cell lineages. MPDs arise from acquired mutations in a pluripotent hematopoietic stem cell. However, the molecular mechanisms leading to the development of these diseases are poorly understood. This review will summarize and evaluate recent advances in our understanding of one particular MPD, PV. (+info)