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

This study was aimed at the characterization of a gene expression signature of the pluripotent hematopoietic CD34(+) stem cell in idiopathic myelofibrosis (IM), which would eventually provide novel pathogenetic insights and/or diagnostic/prognostic information. Aberrantly regulated genes were revealed by transcriptome comparative microarray analysis of normal and IM CD34(+) cells; selected genes were also assayed in granulocytes. One-hundred seventy four differentially expressed genes were identified and in part validated by quantitative polymerase chain reaction. Altered gene expression was corroborated by the detection of abnormally high CD9 or CD164, and low CXCR4, membrane protein expression in IM CD34(+) cells. According to class prediction analysis, a set of eight genes (CD9, GAS2, DLK1, CDH1, WT1, NFE2, HMGA2, and CXCR4) properly recognized IM from normal CD34(+) cells. These genes were aberrantly regulated also in IM granulocytes that could be reliably differentiated from control polycythemia vera and essential thrombocythemia granulocytes in 100% and 81% of cases, respectively. Abnormal expression of HMGA2 and CXCR4 in IM granulocytes was dependent on the presence and the mutational status of JAK2(V617F) mutation. The expression levels of both CD9 and DLK1 were associated with the platelet count, whereas higher WT1 expression levels identified IM patients with more active disease, as revealed by elevated CD34(+) cell count and higher severity score. In conclusion, molecular profiling of IM CD34(+) cells uncovered a limited number of genes with altered expression that, beyond their putative role in disease pathogenesis, are associated with patients' clinical characteristics and may have potential prognostic application.
 ...
PMID:Molecular profiling of CD34+ cells in idiopathic myelofibrosis identifies a set of disease-associated genes and reveals the clinical significance of Wilms' tumor gene 1 (WT1). 1699 May 84

Chromosomal translocations involving the 12q14 band are rarely detected in hematological disorders, and are usually correlated with HMGA2 gene expression. HMGA2 is highly expressed during embryonic cell growth and differentiation, and regulates transcription and chromatin organization, but is rarely detectable in adult tissues. We describe a case of polycythemia vera with a t(12;21)(q14;q22). The 12q14 breakpoint was characterized by fluorescence in situ hybridization analysis using the bacterial artificial chromosome RP11-366L20 containing 3' sequences of the HMGA2 gene. Qualitative and quantitative polymerase chain reaction showed the presence of high levels of HMGA2 gene expression, which were temporarily reduced with hydroxyurea therapy. The present case confirms that involvement of the 12q14 band may be associated with HMGA2 overexpression in chronic Philadelphia chromosome-negative myeloproliferative disease, regardless of the partner chromosome involved in the translocation. Such overexpression may contribute to the pathogenesis of the disease, which otherwise of itself shows a favorable and stable course.
 ...
PMID:HMGA2 overexpression in polycythemia vera with t(12;21)(q14;q22). 1785 65

Philadelphia chromosome-negative myeloproliferative neoplasms (MPN), which include polycythemia vera, essential thrombocythemia, and primary myelofibrosis, are characterized by clonal proliferative hematopoiesis with increased blood cell count. Clonal expansion mechanisms in MPN and related disorders such as myelodysplastic syndromes (MDS) remain to be elucidated. Although mutations in the JAK2 gene lead to a proliferative hematopoiesis in majority of MPN and some MDS, the mutation alone does not cause a clonal expansion. In addition to JAK2 mutations, several genetic abnormalities, including TET2 and polycomb group genes involving epigenetic regulation have been reported in patients with MPN. Moreover, overexpression of HMGA2 due to removal of specific sites in its 3' untranslated region for regulatory let-7 micro RNAs may contribute to the proliferative hematopoiesis with conferring a growth advantage at the level of a hematopoietic stem cell in some cases with MPN.
 ...
PMID:The role of HMGA2 in the proliferation and expansion of a hematopoietic cell in myeloproliferative neoplasms. 2323 64