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)

We measured histone deacetylase (HDAC) activity in 17 patients with primary myelofibrosis (PMF); 19 with other myeloproliferative neoplasm (MPN) and 16 normal volunteers. Significantly elevated HDAC levels were shown in patients with PMF compared with other MPN patients and normal volunteers (p<0.05). Sixteen patients with PMF were also studied for correlation between JAK2 mutation status and HDAC levels; no significant correlation was found. We further correlated HDAC levels with clinical features in PMF: there was no correlation with WBC, platelet counts, Hb levels or degree of bone marrow fibrosis, but HDAC levels were correlated to the degree of splenomegaly. This suggests that HDAC may be recruited as essential thrombocythemia or polycythemia vera progresses into myelofibrosis or PMF progresses into more advanced stage. We then used the qRT-PCR cycle threshold (CT) method to study which HDACs were elevated in PMF. The results showed that, in general, Class 1 HDACs were elevated (HDAC1,2,8) except HDAC3, Class II HDACs were depressed (HDAC4,5) except HDAC6 and 10, and Class III HDACs were generally elevated. The current study may form the basis for using HDAC inhibitor in the treatment of patients with PMF and may implicate a possible role of HDAC in the association of pathogenesis of PMF.
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PMID:Enhanced histone deacetylase enzyme activity in primary myelofibrosis. 1905 66

Myeloproliferation, myeloaccumulation (decreased apoptosis), inflammation, bone marrow fibrosis and angiogenesis are cardinal features of the Philadelphia-negative chronic myeloproliferative neoplasms: essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF). Histone deacetylases (HDACs) have a critical role in modulating gene expression and, accordingly, in the control of cell pathobiology and cancer development. HDAC inhibition has been shown to inhibit tumor growth (impaired myeloproliferation), to modulate the balance between pro- and antiapoptotic proteins in favor of apoptosis (enhanced apoptosis) and also to inhibit angiogenesis. Recently, enhanced HDAC enzyme activity has been found in CD34+cells from patients with PMF, enzyme activity levels highly exceeding those recorded in other chronic myeloproliferative neoplasms (CMPNs). The raised levels correlated to the degree of splenomegaly, suggesting that HDAC might be recruited as ET or PV progresses into myelofibrosis or PMF progresses into a more advanced stage. Accordingly, HDAC inhibition is an obvious novel therapeutic approach in these neoplasms. Using global gene expression profiling of whole blood from patients with CMPNs, we have found a pronounced deregulation of HDAC genes, involving significant up-regulation of the HDAC genes 9 and 11, with the highest expression levels being found in patients with ET (HDAC9 and 11), PMF (HDAC9) and CMPNs (both HDAC9 and HDAC11). Furthermore, we have identified that the HDAC6 gene is progressively expressed in patients with ET, PV and PMF, reflecting a steady accumulation of abnormally expressed HDAC6 during disease evolution. Our results lend further support to HDACs as important epigenetic targets in the future treatment of patients with CMPNs. Since the highest expression levels of HDAC genes were recorded in ET, in PMF and in the entire CMPN group, their down-regulation by HDAC inhibitors might be associated with decreased disease activity, including reduction of splenomegaly.
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PMID:Increased gene expression of histone deacetylases in patients with Philadelphia-negative chronic myeloproliferative neoplasms. 2180 50