Epigenetic regulation of normal and malignant hematopoiesis

Rice, Kim L.; Hormaeche, Itsaso; Licht, Jonathan D.

doi:10.1038/sj.onc.1210755

Cited by 131 publications

(115 citation statements)

References 176 publications

(171 reference statements)

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“…DNMTs catalyse the addition of methyl groups, which are derived from the methyl donor S-adenosyl methionine, onto DNA strands (Rice et al 2007). Based on structural differences in their regulatory N-terminal domains, three distinct families of DNMTs have been classified, namely DNMT1, DNMT2 and DNMT3 (Okano et al 1998, Snykers et al 2009).…”

Section: Discussionmentioning

confidence: 99%

Breed-specific patterns of hepatic gluconeogenesis and glucocorticoid action in pigs

Yang

Albrecht

et al. 2012

Arch. Anim. Breed.

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In the present study, Erhualian and Pietrain pigs were employed to investigate the breedspecific patterns of hepatic gluconeogenesis by detecting the related enzyme mRNA expression, and to analyse the relationship with the hepatic glucocorticoid receptors and 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) expression. Furthermore, hepatic DNA methyltransferase 1 (DNMT1) expression was determined to detect DNA methyltransferase state difference between the two breeds. The results demonstrated that the Erhualian pigs exhibited significantly lower plasma lactate acid concentration, but higher liver lactate acid content than the Pietrain pigs. A significantly higher expression of pyruvate carboxylase (PC), fructose-1, 6-bisphosphatase (FBP) and the mitochondria phosphoenolpyruvate carboxykinase (PCK2) mRNA were observed in Erhualian pigs. The Erhualian pigs demonstrated a significantly higher expression of glucocorticoid receptor and 11β-HSD1 mRNA than the Pietrain pigs, though there was no difference in the hepatic cortisol content between the two breeds. The hepatic DNMT1 mRNA expression in the Erhualian pigs was significantly lower, and the DNMT1 protein content in Erhualian pigs tended to be decreased compared with Pietrain pigs (P=0.066). The results suggest that the Erhualian pigs demonstrated higher hepatic gluconeogenesis capacity in comparison to the Pietrain pigs. The up-regulation of hepatic glucocorticoid receptor and 11β-HSD1 expression may be involved in the enhanced hepatic gluconeogenesis in Erhualian pigs. Moreover, the down-regulation of DNMT1 in Erhualian pigs implies possible involvement of DNA methylation in a breed-specific pattern of hepatic gluconeogenesis.

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Section: Discussionmentioning

confidence: 99%

Breed-specific patterns of hepatic gluconeogenesis and glucocorticoid action in pigs

Yang

Albrecht

et al. 2012

Arch. Anim. Breed.

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“…Examples for opposing enzymes are the mixed-lineage leukemia group histone SET-domain methyl transferases and the JARID1 group and LSD1 histone demethylases, which specifically modify histone H3 Lysine 4 (H3K4). 1 LSD1, the first histone demethylase to be identified, 2 is essential for normal embryonic development 3 and for regulating ES cell self-renewal versus differentiation. 4,5 To our knowledge, the role of LSD1 in adult stem cell maintenance has not yet been addressed.…”

Section: Introductionmentioning

confidence: 99%

Lysine-specific demethylase 1 restricts hematopoietic progenitor proliferation and is essential for terminal differentiation

Sprüssel¹,

Schulte²,

et al. 2012

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“…CpG dinucleotides are enriched at certain gene promoter regions and methylation of these sites may contribute to leukemogenesis through silencing of tumor suppressor genes. 8,9 Aberrant methylation is more common in older cancer patients 10 and is pharmacologically reversible. Azacitidine, an azanucleoside DNA methyltransferase inhibitor that is approved by the US Food and Drug Administration in the related myeloid malignancy myelodysplastic syndrome (MDS), 11 is associated with a low response rate (B20%) in elderly AML patients.…”

Section: Introductionmentioning

confidence: 99%

Safety, efficacy and biological predictors of response to sequential azacitidine and lenalidomide for elderly patients with acute myeloid leukemia

et al. 2011

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Acute myeloid leukemia (AML) is a disease of the elderly. Poor outcomes with standard therapies necessitate novel approaches. Outpatient regimens sufficiently potent and well tolerated to induce remissions and enable continuation therapy may be beneficial. In this phase-1 study, we determined the maximum tolerated dose (MTD) and the efficacy for sequential azacitidine and lenalidomide as remission induction and continuation therapy in elderly, previously untreated patients. We investigated the impact on global DNA methylation and bone marrow cytokines, and sought biological predictors of response. Eighteen patients were enrolled. The MTD was not reached. Median follow-up was 8.2 months (10.3 months for survivors). Common adverse events included fatigue, injection site reactions, constipation, nausea, pruritus and febrile neutropenia. Ten patients responded (56%), and the rate of complete remissions (CRs) or CRs with incomplete recovery of blood counts for evaluable patients was 44% (7/16). The median response duration was 6.2 months. DNA demethylation and changes in bone marrow cytokines were observed; responders had a unique cytokine profile and a trend towards lower methylation levels. Sequential azacitidine and lenalidomide was well tolerated with encouraging clinical and biological activity in previously untreated elderly AML patients. This trial is registered at ClinicalTrials.gov (NCT00890929).

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Epigenetic regulation of normal and malignant hematopoiesis

Cited by 131 publications

References 176 publications

Breed-specific patterns of hepatic gluconeogenesis and glucocorticoid action in pigs

Breed-specific patterns of hepatic gluconeogenesis and glucocorticoid action in pigs

Lysine-specific demethylase 1 restricts hematopoietic progenitor proliferation and is essential for terminal differentiation

Safety, efficacy and biological predictors of response to sequential azacitidine and lenalidomide for elderly patients with acute myeloid leukemia

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