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Renal biopsy cases in myeloproliferative neoplasms (MPN).

ABSTRACT: We performed renal biopsy in three cases complicated by myeloproliferative neoplasms (MPN). Although several cases of glomerulonephritis associated with MPN have been reported, the etiologies of the renal disorders were not established (Plomley et al., Aust NZ J Med, 13:125-129, 1983; Sharma et al., Nephron, 69:361, 1995; Kanauchi et al., Intern Med, 33:36-40, 1994; Kasuno et al., Nephrol Dial Transplant, 12:212-215, 1997; Au et al., Am J Kid Dis, 34:889-893, 1999; Kosch et al., Nephrol Dial Transplant, 15:1710-1711, 2000; Oymak et al., Nephron, 86:346-347, 2000; Chun et al., Am J Nephrol, 20:344-346, 2000; Chung et al., Am J Nephrol, 22:397-401, 2002; Asaba et al., Clin Exp Nephrol, 7:296-300, 2003; Haraguchi et al., Clin Exp Nephrol, 10:74-77, 2006; Saigusa et al., J Nephrol, 19:656-658, 2006; Okuyama et al., Clin Nephrol, 6:412-415, 2007; Nishi et al., Clin Nephrol, 5:393-398, 2010; Ulusoy et al., Intern Med, 49:2477, 2010). A review of previous reports of renal biopsy cases with MPN in the English literature suggested that circulation control is important for the treatment of renal disorders that mimic glomerulonephritis in MPN.

SUBMITTER: Fujita K

PROVIDER: S-EPMC5411553 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Renal biopsy cases in myeloproliferative neoplasms (MPN).

Fujita Kumi K Hatta Kazuhiro K

CEN case reports 20130312 2

We performed renal biopsy in three cases complicated by myeloproliferative neoplasms (MPN). Although several cases of glomerulonephritis associated with MPN have been reported, the etiologies of the renal disorders were not established (Plomley et al., Aust NZ J Med, 13:125-129, 1983; Sharma et al., Nephron, 69:361, 1995; Kanauchi et al., Intern Med, 33:36-40, 1994; Kasuno et al., Nephrol Dial Transplant, 12:212-215, 1997; Au et al., Am J Kid Dis, 34:889-893, 1999; Kosch et al., Nephrol Dial Tra ...[more]

PMID: 28509296

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Project description:Even though mutations in epigenetic regulators frequently occur in myeloproliferative neoplasms, their effects on the epigenome have not been well studied. Furthermore, even though primary myelofibrosis (PMF) has a markedly worse prognosis compared to essential thrombocytosis (ET) or polycythemia vera (PV), the molecular distinctions between these subgroups are not well elucidated. We performed the HELP (HpaII tiny fragment enriched by LM-PCR) assay to study genome-wide methylation in PV, ET and PMF samples compared with healthy controls. We determined that PV and ET are characterized by aberrant promoter hypermethylation while PMF is an epigenetically distinct subgroup characterized by both aberrant hyper and hypomethylation. Aberrant hypomethylation in PMF was seen to occur in non CpG island loci, demonstrating further qualitative differences between the disease subgroups. The differentially methylated genes in PV and ET were involved predominantly in cell signaling pathways and were enriched for binding sites of GATA1 and other transcription factors. In contrast, aberrantly methylated genes in PMF were involved in inflammatory pathways and were enriched for NF1 (NFI), LEF1 and other transcription factors. Within the PMF subgroup, cases with ASXL1 disruptions formed an epigenetically distinct subgroup with relatively increased methylation. Cases of MPNs with TET2 mutations demonstrated decreased levels of hydroxymethylation and distinct set of hypermethylated genes. In contrast, the JAK2V617F mutation did not drive epigenetic clustering within MPNs. Finally, the significance of aberrant methylation was demonstrated by sensitivity of MPN derived cell lines to decitabine. These results demonstrate epigenetic differences between PMF and PV/ET and reveal methylomic signatures of ASXL1 and TET2 mutations. The study population consisted of 26 MPN patients (6 cases of ET, 8 cases of PV and 12 cases of PMF) and 3 healthy controls. Individual HpaII restriction digest profiles were compared to an internal MspI digest control, to yield differentially methylated fragments for every sample. The purpose of this study was to assess genome wide patterns of DNA methylation across the MPN stratified by disease class.

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Renal biopsy cases in myeloproliferative neoplasms (MPN).

Publications

Renal biopsy cases in myeloproliferative neoplasms (MPN).

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