Myelodysplastic syndrome genetics

Jump to navigation Jump to search

Myelodysplastic syndrome Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Myelodysplastic syndrome from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

Chest X Ray

Echocardiography and Ultrasound

CT

MRI

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Myelodysplastic syndrome genetics On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Myelodysplastic syndrome genetics

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Myelodysplastic syndrome genetics

CDC on Myelodysplastic syndrome genetics

Myelodysplastic syndrome genetics in the news

Blogs on Myelodysplastic syndrome genetics

Directions to Hospitals Treating Myelodysplastic syndrome

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.

References


Template:WikiDoc Sources