Myelodysplastic syndrome genetics: Difference between revisions
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==Overview== | ==Overview== | ||
Myelodysplastic syndrome is caused by the clonal proliferation of hematopoietic precursors. Inactivation or mutation of tumor supressor gene [[TP53]] leads to leukemic progression of Myelodysplastic syndrome. | |||
==Genetics== | ==Genetics== | ||
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Overall, the mutations in the RUNX1/AML1 are the most common point mutations described in MDS to date but RUNX1/AML1 mutations have no distinct hematologic phenotype and are most commonly associated with previous radiation exposure and with a higher risk disease (especially with excess blasts). | Overall, the mutations in the RUNX1/AML1 are the most common point mutations described in MDS to date but RUNX1/AML1 mutations have no distinct hematologic phenotype and are most commonly associated with previous radiation exposure and with a higher risk disease (especially with excess blasts). | ||
Hypermethylation leading to silencing of the p151NK-4b gene is also common in MDS. This phenomenon occurs in up to 80% of the cases with advanced MDS. The silencing of this gene can be reversed by the uyse of demethylating agents such as 5-azacytidine. These agents are pyrimidine analogues that inhibit DNA methyltransferase activity and could improve MDS hematopoiesis by reversing aberrant gene methylation and permitting cellular differentiation. | Hypermethylation leading to silencing of the p151NK-4b gene is also common in MDS. This phenomenon occurs in up to 80% of the cases with advanced MDS. The silencing of this gene can be reversed by the uyse of demethylating agents such as 5-azacytidine. These agents are pyrimidine analogues that inhibit DNA methyltransferase activity and could improve MDS [[hematopoiesis]] by reversing aberrant [[gene]] methylation and permitting cellular differentiation. | ||
A number of studies suggest that erythropoietin (EPO) signaling and STAT5 activation is abnormal in MDS. The SOCS1 gene is hypermethylated in 31% of MDS patients which is associated with increased activity of the JAK/STAT pathway. | A number of studies suggest that [[erythropoietin]] (EPO) signaling and STAT5 activation is abnormal in [[MDS]]. The SOCS1 gene is [[hypermethylated]] in 31% of MDS patients which is associated with increased activity of the [[JAK/STAT]] pathway. | ||
Microsatellite instability involving defects in the DNA mismatch repair system has been identified in some MDS patients, especially those with therapy-related disease. | [[Microsatellite]] instability involving defects in the DNA mismatch repair system has been identified in some MDS patients, especially those with therapy-related disease. | ||
The TP53 tumor suppressor gene, which regulates cell cycle progression, DNA repair and apoptosis is mutated in 5-10% of MDS cases. Inactivation of the TP53 gene may contribute to the leukemic progression from MDS. | The [[TP53]] tumor suppressor gene, which regulates [[cell cycle]] progression, [[DNA]] repair and [[apoptosis]] is mutated in 5-10% of MDS cases. Inactivation of the [[TP53]] gene may contribute to the leukemic progression from [[MDS]]. | ||
==References== | ==References== | ||
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[[Category:Disease]] | [[Category:Disease]] | ||
[[Category:Types of cancer]] | [[Category:Types of cancer]] | ||
[[Category:Oncology]] | [[Category:Oncology]] | ||
[[Category:Hematology]] | [[Category:Hematology]] | ||
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Revision as of 15:12, 18 August 2015
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Myelodysplastic syndrome Microchapters |
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Differentiating Myelodysplastic syndrome from other Diseases |
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Diagnosis |
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Treatment |
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Case Studies |
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Myelodysplastic syndrome genetics On the Web |
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American Roentgen Ray Society Images of Myelodysplastic syndrome genetics |
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Risk calculators and risk factors for Myelodysplastic syndrome genetics |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Myelodysplastic syndrome is caused by the clonal proliferation of hematopoietic precursors. Inactivation or mutation of tumor supressor gene TP53 leads to leukemic progression of Myelodysplastic syndrome.
Genetics
| Abnormality | Frequency in MDS |
|---|---|
| -5/del(5q) | 10-20% |
| +8 | 10% |
| -7/del(7q) | 5-10% |
| -Y | 10% |
| 17p- | 7% |
| del(20q) | 5-6% |
| t(11q23) | 5-6% |
| complex karyotype | 10-20% |
Overall, the mutations in the RUNX1/AML1 are the most common point mutations described in MDS to date but RUNX1/AML1 mutations have no distinct hematologic phenotype and are most commonly associated with previous radiation exposure and with a higher risk disease (especially with excess blasts).
Hypermethylation leading to silencing of the p151NK-4b gene is also common in MDS. This phenomenon occurs in up to 80% of the cases with advanced MDS. The silencing of this gene can be reversed by the uyse of demethylating agents such as 5-azacytidine. These agents are pyrimidine analogues that inhibit DNA methyltransferase activity and could improve MDS hematopoiesis by reversing aberrant gene methylation and permitting cellular differentiation.
A number of studies suggest that erythropoietin (EPO) signaling and STAT5 activation is abnormal in MDS. The SOCS1 gene is hypermethylated in 31% of MDS patients which is associated with increased activity of the JAK/STAT pathway.
Microsatellite instability involving defects in the DNA mismatch repair system has been identified in some MDS patients, especially those with therapy-related disease.
The TP53 tumor suppressor gene, which regulates cell cycle progression, DNA repair and apoptosis is mutated in 5-10% of MDS cases. Inactivation of the TP53 gene may contribute to the leukemic progression from MDS.