Myelodysplastic syndromes (MDS) are influenced by a number of chromosomal, epigenetic, or mutational abnormalities.1-3 Understanding these alterations can help healthcare professionals diagnose MDS and determine prognosis and treatment options.1
Adapted from: Bejar R et al. J Clin Oncol. 2011;29(5):504-515, and Issa JP. Blood. 2013;121(19):3811‑3817.
Chromosomal abnormalities
The anatomy of a chromosome is important in our understanding of MDS and the types of abnormalities that occur.
- Each chromosome is made up of DNA. DNA winds around histones, which are proteins involved in holding the DNA in a compact shape4
- The centromere helps keep the chromosomes properly aligned by serving as an attachment site for the halves of each chromosome. This gives the chromosome its characteristic shape4
- The arms of the chromosome are on either side of the centromere. The short arm, or upper portion, is called the p arm. The long arm, or lower portion, is called the q arm. These are important when denoting the location of specific genes and abnormalities4
Different types of chromosomal abnormalities can occur. These may be changes to the chromosome structure or number, such as deletions, duplications, inversions, and translocations.5,6
Deletions, del or -( )7-10
A portion of, or the entire chromosome, is missing5 |
Inversions, inv( )
A portion of a chromosome breaks off, flips around, and reattaches in the wrong direction5 |
Duplications
A portion of a chromosome is duplicated, resulting in extra genetic material5 |
Translocations, t( )
Part of the chromosomal material transfers from one chromosome to another5 |
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Certain inversions are considered AML |
|
Certain translocations are considered AML |
Deletions, del or -( )7-10
A portion of, or the entire chromosome, is missing5 |
|
Inversions, inv( )
A portion of a chromosome breaks off, flips around, and reattaches in the wrong direction5 |
Certain inversions are considered AML |
Duplications
A portion of a chromosome is duplicated, resulting in extra genetic material5 |
|
Translocations, t( )
Part of the chromosomal material transfers from one chromosome to another5 |
Certain translocations are considered AML |
AML, acute myeloid leukemia.
Chromosomal abnormalities are proven to be useful both diagnostically and prognostically.1
- del(5q) has a favorable prognosis1
- This is the most common chromosomal abnormality in MDS (incidence ≈15%)
- del(7q) has a poor prognosis1
- Trisomy 8 confers an intermediate risk, but patients may respond well to immunosuppressive therapy1
- Loss of Y (-Y) and del(20q) have a favorable risk1
Epigenetic abnormalities
Epigenetic abnormalities are changes that alter gene expression but do not change the DNA sequence. Some examples that are often abnormal in MDS are2:
- DNA methylation
- Histone modification
- Micro-RNA expression
These types of changes may co-exist with other cytogenetic changes and gene mutations.
Mutational abnormalities
Genetic abnormalities, or mutations, alter the sequence or expression of individual genes.1,3,11 One or more gene mutations are found in almost all MDS patients.1 Mutations in genes SF3B1, TET2, and ASXL1 are the most common, and dozens more have been found in recent years.1,3
Genetic mutations that alter the sequence or expression of the individual genes1,3,11 |
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Mutations within components of the spliceosome are found in up to 60% of MDS cases.11
Spliceosome mutations that alter the abundance or function of target genes through aberrant mRNA splicing3,11 |
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See Molecular Analysis.