Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032463 (polycythemia vera)
 3,374 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to determine the relationship between bone marrow (bm) endosteal cells (EDC) and hemopoietic progenitors, we have analyzed the immunophenotype of EDC using various antibodies (Ab) against mesenchymal antigens. The Ab were applied on paraffin sections of normal bm (iliac crest, n=17; talus, n=1; phalanx, n=1), myeloregenerative bm (after chemotherapy), and hematologic disorders (acute myeloid leukemia (AML), n=8; chronic myeloid leukemia (CML), n=6; myelodysplastic syndromes (MDS), n=14; severe aplastic anemia (SAA), n=4; essential thrombocythemia (ET), n=2; idiopathic (primary) osteomyelo-fibrosis (IMF), n=1; polycythemia vera (PV), n=1). In normal bm, EDC were found to react with Ab against vimentin, tenascin, alpha-smooth muscle actin, osteocalcin, CD51, and CD56, but did not react with Ab against CD3, CD15, CD20, CD34, CD45, CD68, or CD117. An identical phenotype of EDC was found in AML, MDS, SAA, ET, IMF, PV, myeloregenerative bm, and peripheral bones lacking active hemopoiesis (talus, phalanx). In patients with CML, EDC reacted with Ab to CD51, but did not react with Ab to CD56. Based on their unique antigen profile, EDC were enriched from normal bm by enzyme digestion and cell sorting. However, these enriched cells (CD56+, CD45-, CD34-) did not give rise to hemopoietic cells under the culture conditions used, i.e. in the presence of the growth factors IGF-1, bFGF, SCF, IL-3, and GM-CSF Together, our data do not support the hypothesis that EDC are totipotent mesenchymal progenitors giving rise to hemopoietic cells.
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PMID:Immunophenotypic characterization of human bone marrow endosteal cells. 1039 6

Chronic myeloprolifeative diseases (CMPD) are clonal hematopoietic stem cell disorders characterized by excessive proliferation and production of one or more of the myeloid cells and are subclassified according to the predominant cells, such as chronic myelogenous leukemia (CNL), chronic eosinophilic leukemia (CEL), polycythemia vera (PV), essential thrombocythemia (ET) and chronic idiopathic myelofibrosis (CIMF). This brief review focuses on the characteristic morphology of each clinical entity and the useful cytochemical (including leukocyte alkaline phosphatase, myeloperoxidase, butyrate esterase, chloroacetate esterase and cyanide-resistant peroxidase) and immunohistochemical (including von Willebrand factor/CD61, keratin, tryptase, CD117, CD68 (PGM-1), c-Mpl and bFGF) stains for differential diagnosis.
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PMID:The role of morphology, cytochemistry and immunohistochemistry in the diagnosis of chronic myeloproliferative diseases. 1243 Aug 92

BCR-ABL is a causative tyrosine kinase (TK) of chronic myelogenous leukemia (CML). In CML patients, although myeloid cells are remarkably proliferating, erythroid cells are rather decreased and anemia is commonly observed. This phenotype is quite different from that observed in polycythemia vera (PV) caused by JAK2 V617F, whereas both oncogenic TKs activate common downstream molecules at the level of hematopoietic stem cells (HSCs). To clarify this mechanism, we investigated the effects of BCR-ABL and JAK2 V617F on erythropoiesis. Enforced expression of BCR-ABL but not of JAK2 V617F in murine LSK (Lineage(-)Sca-1(hi)CD117(hi)) cells inhibited the development of erythroid cells. Among several signaling molecules downstream of BCR-ABL, an active mutant of N-Ras (N-RasE12) but not of STAT5 or phosphatidylinositol 3-kinase (PI3-K) inhibited erythropoiesis, while N-RasE12 enhanced the development of myeloid cells. BCR-ABL activated Ras signal more intensely than JAK2 V617F, and inhibition of Ras by manumycin A, a farnesyltransferase inhibitor, ameliorated erythroid colony formation of CML cells. As for the mechanisms of Ras-induced suppression of erythropoiesis, we found that GATA-1, an erythroid-specific transcription factor, blocked Ras-mediated mitogenic signaling at the level of MEK through the direct interaction. Furthermore, enforced expression of N-RasE12 in LSK cells derived from p53-, p16(INK4a)/p19(ARF)-, and p21(CIP1/WAF1)-null/wild-type mice revealed that suppressed erythroid cell growth by N-RasE12 was restored only by p21(CIP1/WAF1) deficiency, indicating that a cyclin-dependent kinase (CDK) inhibitor, p21(CIP1/WAF1), plays crucial roles in Ras-induced suppression of erythropoiesis. These data would, at least partly, explain why respective oncogenic TKs cause different disease phenotypes.
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PMID:BCR-ABL but not JAK2 V617F inhibits erythropoiesis through the Ras signal by inducing p21CIP1/WAF1. 2066 70

Acute erythroid leukemia in children is very rare. Here is a case of erythroleukemia in a child of age 1.5 years, which was diagnosed on peripheral smear, bone marrow examination, cytochemistry but was confirmed on immunophenotyping. CD45 versus side scatter demonstrated blast population (29%) expressing CD45 of variable intensity (dim to negative). The myeloid nature of blast population showed bright expression of cytoplasmic myeloperoxidase (MPO), heterogenous positivity of CD117 and dim expression of CD13, CD33. These blasts also showed bright positivity for CD71 which showed erythroid nature of blasts. Flow cytometry can be comprehensive enough to completely subtype cases of leukemias/myelodysplastic syndromes, polycythemia rubra vera, non-neoplastic conditions like reactive erythroid hyperplasia following immunosuppressive therapy or viral infections or nutritional deficiencies, unlyzed RBCs or thrombocytosis which may mimic acute erythroid leukemia on flow cytometry.
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PMID:Childhood acute erythroleukemia diagnosis by flow cytometry. 2139 10

We studied 24 spleens with extramedullary hematopoietic proliferation (EMHP), a key feature of advanced-stage Philadelphia chromosome-negative myeloproliferative neoplasms, obtained from 24 patients (14 primary myelofibrosis, 7 polycythemia vera and 3 unclassifiable). Hematoxylin and eosin, reticulin and trichrome stains, and immunohistochemical stains for myeloperoxidase, glycophorin-C, CD42b, CD34, CD117, CD8, nerve growth factor receptor and smooth muscle actin were evaluated. Clinical information was correlated with the morphological findings. Three distinct histological patterns of EMHP were recognized: diffuse (12), nodular (5), and mixed-nodular and diffuse (7). The preponderant lineage was granulocytic in diffuse, trilineage in nodular and erythroid in mixed EMHP. Erythropoiesis was largely intravascular, granulopoiesis was within the splenic cords and megakaryopoiesis was observed in both locations. The stromal changes paralleled the histological pattern with preservation of the splenic stromal and vascular architecture in the diffuse areas as opposed to areas of nodular EMHP. The morphological features of the splenic EMHP did not correlate with specific subtypes of myeloproliferative neoplasms. The mean duration of follow-up from initial diagnosis was 80 months. A total of 15 of the 24 patients died of disease: 8 of 12 (67%) with diffuse, 2 of 5 (40%) with nodular and 5 of 7 (71%) with mixed growth patterns. The mean duration from diagnosis to splenectomy was shorter in patients with diffuse (83 months) as compared with those with nodular EMHP (127 months). Our study demonstrates that splenic extramedullary hematopoietic proliferation in Philadelphia chromosome-negative myeloproliferative neoplasms shows distinct histological patterns that do not correlate with disease subtypes, but appear to suggest a trend between the histological patterns and clinical behavior. These results suggest a different biology of the disease in the nodular and diffuse extramedullary hematopoietic proliferation groups.
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PMID:Splenic extramedullary hematopoietic proliferation in Philadelphia chromosome-negative myeloproliferative neoplasms: heterogeneous morphology and cytological composition. 2238 63