Aberrant methylation of the negative regulators RASSFIA, SHP‐1 and SOCS‐1 in myelodysplastic syndromes and acute myeloid leukaemia

@article{Johan2005AberrantMO,
  title={Aberrant methylation of the negative regulators RASSFIA, SHP‐1 and SOCS‐1 in myelodysplastic syndromes and acute myeloid leukaemia},
  author={Muhammad Farid Johan and David T. Bowen and Marion E. Frew and Anne C. Goodeve and John T. Reilly},
  journal={British Journal of Haematology},
  year={2005},
  volume={129}
}
Mutations in the receptor tyrosine kinase (RTK/RAS) signalling pathway frequently provide a proliferative signal in myeloid malignancies. However, the role of RASSF1A, SHP‐1 and SOCS‐1, negative regulators of RTK/RAS signalling, has not been extensively investigated in the myelodysplastic syndromes (MDS) or acute myeloid leukaemia (AML). This study employed methylation‐specific polymerase chain reaction (MS‐PCR) to determine if aberrant promotor methylation of RASSF1A, SHP‐1 and SOCS‐1 is… 

Hypermethylation of the suppressor of cytokine signalling‐1 (SOCS‐1) in myelodysplastic syndrome

Demethylation experiments provided direct evidence that aberrant methylation of SOCS‐1 induces transcriptional silencing in myeloid cells and for the first time evidence that the activity of the Janus kinase/STAT pathway is increased in primary patient samples showing SOCS-1 hypermethylation is provided.

Clinical implications of SOCS1 methylation in myelodysplastic syndrome

This is the first report to demonstrate the clinical relevance of SOCS1 methylation in MDS and it may play an important role in the pathogenesis of MDS, especially among patients with high‐risk subtypes.

Epigenetic inactivation of suppressors of cytokine signalling in Philadelphia‐negative chronic myeloproliferative disorders

Methylation of SOCS3 and, to a lesser extent, SOCS1 and PTPN6 is a frequent event in both JAK2V617F‐positive and ‐negative CMPD and may act as an alternative or complementary mechanism to JAK 2 mutations, enhancing cytokine signal transduction.

Clinical implications of SOCS1 methylation in myelodysplastic

This is the first report to demonstrate the clinical relevance of SOCS1 methylation in MDS and suggest it may play an important role in the pathogenesis of MDS, especially among patients with high-risk subtypes.

Epigenetic alterations complement mutation of JAK2 tyrosine kinase in patients with BCR/ABL-negative myeloproliferative disorders

The results suggest that epigenetic inactivation of SOCS-1 may be a complementary mechanism to the JAK2V617F mutation in the pathogenesis of MPD that leads to dysregulation of JAK-STAT signal transduction and thus contributes to growth factor hypersensitivity.

The SOCS‐1 gene methylation in chronic myeloid leukemia patients

The results of this study showed no correlation between SOCS1 gene Exon‐2 hypermethylation and CML development or progression, and might be indicating hypomethylation in CML patients.

Hyper-methylation of the SOCS2 Promoter in AML: An Unexpected Association with the FLT3-ITD Mutation

It is speculated that SOCS2 interacts with an aspect of the signalling complex to inhibit cell growth in patients with high white blood cell count and a FLT3-ITD, and silencing SOCS1 is necessary for leukemia progression.

Role of DNA methylation in the pathogenesis and treatment of myelodysplastic syndromes.

These studies show that even though DNA methylation has been studied extensively in MDS, its role in prognosis and response to therapy is still unclear and the use of deep sequencing and genome-wide methylome analysis will potentially uncover prognostic signatures and reveal the complexity of epigenetic dysregulation in this disease.

Methylation of the suppressor of cytokine signaling 3 gene (SOCS3) in myeloproliferative disorders

SOCS3 transcript levels were highest in patients with polycythemia vera and other JAK2 V617F positive myeloproliferative disorders, consistent with SOCS3 being a target gene of JAK/STAT5 signaling, and methylation status was not significantly correlated with survival or other clinical variables.
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