Increased incidence of monoclonal B-cell infiltrate in chronic myeloproliferative disorders.
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A total of 106 trephine biopsy specimens with clinical, laboratory and pathology findings corresponding to chronic myeloproliferative disorders (CMPD) were analyzed to reveal the nature of the lymphoid infiltrate in the bone marrow. Histological investigation in 31 chronic myeloid leukemia (CML), 29 CMPDs not otherwise specified (CMPD-NOS), 28 essential thrombocytosis (ET), 15 polycythemia vera (PV) and three chronic eosinophilic leukemia/hypereosinophilic syndrome (CEL/HES) exhibited in 32% various amounts of lymphocytic infiltrate of sparsely to moderately diffuse or nodular types in the bone marrow, but the reactive or coinciding lymphomatous nature could not be revealed by histology alone in the majority of cases. PCR analysis of the immunoglobulin heavy chain (IgH) gene rearrangement was successfully performed in 81 out of the 106 DNA specimens extracted from formol-paraffin blocks. Out of the 81 samples with good-quality DNA, 18 gave a single or double discrete amplification band(s), which was reproducible only in four specimens. Sequencing finally proved monoclonal B-cell population of both pre- and postfollicular origin in all four samples (5%), one CML and three CMPD-NOS. Detailed clinical and pathological investigations indicated overt B-cell malignant lymphoma with clonal relationship to the CMPD in two out of these four patients. We conclude that detailed molecular analysis of IgH gene rearrangement in bone marrow samples of CMPD patients is needed to identify the true monoclonal B-cell infiltration, which-even without overt malignant lymphoma-may occur in this group of disorders. Modern Pathology (2004) 17, 1521-1530, advance online publication, 16 July 2004; doi:10.1038/modpathol.3800225. (+info)
Heparin-induced thrombocytopenia and thrombosis in a patient with polycythemia vera.
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A 75-year-old Japanese woman with polycythemia vera was admitted to our hospital in January 2003 with suspected pulmonary thromboembolism. After administration of heparin, platelet count decreased from 1,694 x 10(9)/l on admission to 60 x 10(9)/l on hospital day 14. The patient developed acute limb embolism and transient cerebral ischemic attack on days 17 and 25, respectively. Signs and symptoms mimicked those of disseminated intravascular coagulation. Antibodies against heparin and platelet factor 4 complexes were detected in serum, and a diagnosis of heparin-induced thrombocytopenia and thrombosis was made. Argatroban treatment improved thrombocytopenia and hypercoagulable state. (+info)
Retroperitoneal hemorrhage following bone marrow biopsy.
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We report the case of an elderly woman with polycythemia vera submitted to bone marrow biopsy who developed retroperitoneal hemorrhage as a result of direct penetration of the needle through the iliac crest, with damage to the iliolumbar artery, the first branch of the hypogastric artery. (+info)
Diagnostic value of serum erythropoietin level in patients with absolute erythrocytosis.
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BACKGROUND AND OBJECTIVES: The diagnosis of polycythemia vera (PV) is based on clinical and biological criteria defined by either the Polycythemia Vera Study Group (PVSG) or the World Health Organization (WHO). Both the PVSG and WHO PV criteria have proved helpful and are extensively used, yet diagnostic strategies and scheduling of biological investigations vary. We assessed the value of measuring serum erythropoietin (Epo) as a first intention diagnostic test in patients with absolute erythrocytosis (AE). DESIGN AND METHODS: Serum and bone marrow (BM) samples of 241 patients with a suspicion of erythrocytosis were collected in 8 hospital centers. One hundred and ninety had an absolute erythrocytosis (116 had PV, 66 had secondary erythrocytosis and 4 had idiopathic erythrocytosis). Serum Epo was assayed (ELISA) in 186. Statistical analysis (ROC curves) was used to define serum Epo thresholds that were specific for PV and secondary erythrocytosis and to analyze the diagnostic value of a low or high serum Epo level. RESULTS: A large majority of PV patients (87% or 101/116) had a serum Epo level below the normal range in healthy patients (3.3 IU/L), giving this value a specificity of 97% with a 97.8% positive predictive value for the diagnosis of PV. Statistical analysis (ROC curves) defined two thresholds allowing a specific and direct diagnosis of 65.6% (65/99) of untreated PV (Epo < 1.4 IU/L) and 19.7% (13/66) of those with secondary erythrocytosis (Epo > 13.7 IU/L). INTERPRETATION AND CONCLUSIONS: Based on these data, we propose that measurement of serum Epo level, a simple, reliable and inexpensive test, should be considered as a first intention diagnostic test for patients with absolute erythrocytosis. (+info)
Early down-regulation of Bcl-xL expression during megakaryocytic differentiation of thrombopoietin-induced CD34+ bone marrow cells in essential thrombocythemia.
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BACKGROUND AND OBJECTIVES: Essential thrombocythemia (ET) is a chronic myeloproliferative disorder with abnormal megakaryocyte/platelet production. Recent studies have found that Bcl-xL, as a member of the bcl-2 family of proteins that inhibit apoptosis, is essential in megakaryocytic differentiation. In this study the expression of Bcl-xL was evaluated during megakaryocytic differentiation in ET patients. DESIGN AND METHODS: To study the role of Bcl-xL in megakaryocyte differentiation, we evaluated the effect of small interfering RNA (siRNA) on the expression of Bcl-xL. CD34+ cells from patients with ET, chronic myeloid leukemia (CML), polycythemia vera (PV) and normal individuals were cultured in serum-free medium supplemented with thrombopoietin (TPO). Immunocytochemical staining and flow cytometric analysis were used to evaluate the Bcl-xL expression during megakaryocytic differentiation of CD34+ cells. RESULTS: When exposured to si-Bcl-xL, the percentage of K562 cells induced into megakaryocytes in 72 hours was lower than the corresponding percentage of control cells. CD41a+ cells from the three groups of patients and the control group were cultured. At day 10, the percentage of Bcl-xL- cells in CD41a+ cells from ET patients was 61.0+/-28.1%, which was significantly higher than that from patients with CML (2.5+/-20.9%), PV (33.6+/-10.0%) or control subjects (15.1+/-13.0%).] INTERPRETATION AND CONCLUSIONS: These results demonstrate that Bcl-xL is down-regulated early during in vitro differentiation of megakaryocytes from ET patients; this might reflect an early entry of megakaryocytes into a degenerating mature stage. (+info)
The effects of hydroxyurea on PRV-1 expression in patients with essential thrombocythemia and polycythemia vera.
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The study was designed to investigate the influence of hydroxyurea (HU) treatment on PRV-1 expression. Eighteen newly diagnosed patients with essential thrombocythemia (ET) or polycythemia vera (PV) were included. HU significantly increased PRV-1 gene expression in the early stage of treatment. (+info)
High telomerase activity in granulocytes from clonal polycythemia vera and essential thrombocythemia.
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Essential thrombocythemia (ET) and polycythemia vera (PV) are chronic myeloproliferative disorders that share the involvement of a multipotent progenitor cell and dominance of the transformed clone over normal hematopoiesis. On the other hand, the heterogeneity of these diseases with respect to clonal development from a common progenitor has been well established. To identify useful prognostic indicators, we analyzed telomerase activity (TA), a known marker of neoplastic proliferation, in granulocytes (PMNs) and mononuclear cells (MNCs) from 22 female patients with ET and PV. Clonality status was determined by investigation of X chromosome inactivation patterns (XCIPs). We found a statistically significant positive correlation between high TA and monoclonal pattern of XCIP. Therefore, our data suggest that the use of multiple tumor markers may contribute to a better understanding of the deregulated physiology of these disorders and provide useful prognostic factors. (+info)
Anagrelide-associated cardiomyopathy in polycythemia vera and essential thrombocythemia.
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A comprehensive database inquiry at our institutions identified 11 patients with echocardiogram-documented idiopathic cardiomyopathy that post-dated a diagnosis of either polycythemia vera or essential thrombocythemia. Anagrelide therapy was temporally associated with the particular complication in 6 patients, all of whom experienced symptomatic and/or objective improvement after drug discontinuation. (+info)