Treatment related MDS (t-MDS)

T-MDS treatment related MDS
Treatment-related myelodysplastic syndromes (t-MDS), also known as therapy-related myelodysplastic syndromes, is a specific type of MDS that occurs as a result of previous cancer treatments, such as chemotherapy or radiation therapy. It is considered a secondary form of MDS, distinct from de novo or primary MDS, which arises spontaneously without a known cause. t-MDS represents 10-20% of all MDS cases.
The risk of developing t-MDS is affected by several factors:
- The type and dose of previous treatments
- Exposure to certain chemotherapeutic agents
- Radiation therapy
- Individual patient susceptibility
In some patients, it can happen 4 to 7 years after treatment with alkylating agents, and it can also occur if they were treated with topoisomerase II inhibitors. t-MDS with prior use of alkylating agents can cause problems with chromosomes 5 and 7 [5/del (5q)] and 7 [7/del (7q)] in the cells of the bone marrow. For some people, t-MDS shows up slowly and affects the way blood cells develop. In other cases, usually with history of treatment with topoisomerase II inhibitors, it is more common to turn into a type of cancer called acute myeloid leukemia (AML) with changes involving chromosome bands 11q23 or 21q22. The number of people diagnosed with t-MDS is increasing as more patients are surviving their first cancer through receiving intensive treatments.
DNA repair mechanisms play a crucial role in keeping our genetic information intact. There are different pathways that help fix damaged DNA, such as mismatch repair, base excision repair, nucleotide excision repair, and DNA double-strand break repair. When these repair proteins don't work properly, it can be linked to the development of leukemia that happens as a result of cancer treatments. The most common mutation, seen in 28-38% of patients with t-MDS is abnormal p53 activity, which plays a very important role in DNA repair, and is not so commonly seen in other MDS types like de novo MDS or AML (not related to prior treatments with anti-cancer drugs).
Telomeres are like protective caps at the ends of our chromosomes. These telomers are made up of noncoding DNA and help prevent chromosomes from sticking together or getting damaged. Think of them like the caps on shoelaces that keep them from fraying or tangling. Their role is to maintain the stability and integrity of our chromosomes, which is important for the proper functioning of our cells. Every time a cell in our body divides, the telomeres (which are protective structures at the ends of our chromosomes) get a little bit shorter. This shortening of telomeres happens with each division and over time it can limit the number of divisions a cell can go through before it stops dividing altogether. This process is called cell senescence. Telomere shortening is also connected to genetic instability, which means it can cause changes or abnormalities in our genes.
Analysis of changes in telomere length in serial blood samples from patients who developed t-MDS/AML after autologous hematopoietic cell transplantation (HCT) revealed accelerated telomere shortening in t-MDS/ AML patients when compared with matched controls who did not develop t-MDS/AML.
Studying treatment-related MDS offers valuable insights into leukemia development, and it may be applicable to de-novo MDS and AML in the elderly, which means there are more tools to further our understanding of MDS and AML. Healthcare providers now have a range of effective options, including targeted therapies, immunomodulatory agents, supportive care, and stem cell transplantation. Genetic profiling and personalized medicine further enhance treatment plans. As our understanding of MDS evolves, breakthroughs are expected to provide even better tailored therapies.
REFERENCE:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3437333
https://www.nature.com/articles/s41375-023-01864-6
T-MDS treatment related MDS
Treatment-related myelodysplastic syndromes (t-MDS), also known as therapy-related myelodysplastic syndromes, is a specific type of MDS that occurs as a result of previous cancer treatments, such as chemotherapy or radiation therapy. It is considered a secondary form of MDS, distinct from de novo or primary MDS, which arises spontaneously without a known cause. t-MDS represents 10-20% of all MDS cases.
The risk of developing t-MDS is affected by several factors:
- The type and dose of previous treatments
- Exposure to certain chemotherapeutic agents
- Radiation therapy
- Individual patient susceptibility
In some patients, it can happen 4 to 7 years after treatment with alkylating agents, and it can also occur if they were treated with topoisomerase II inhibitors. t-MDS with prior use of alkylating agents can cause problems with chromosomes 5 and 7 [5/del (5q)] and 7 [7/del (7q)] in the cells of the bone marrow. For some people, t-MDS shows up slowly and affects the way blood cells develop. In other cases, usually with history of treatment with topoisomerase II inhibitors, it is more common to turn into a type of cancer called acute myeloid leukemia (AML) with changes involving chromosome bands 11q23 or 21q22. The number of people diagnosed with t-MDS is increasing as more patients are surviving their first cancer through receiving intensive treatments.
DNA repair mechanisms play a crucial role in keeping our genetic information intact. There are different pathways that help fix damaged DNA, such as mismatch repair, base excision repair, nucleotide excision repair, and DNA double-strand break repair. When these repair proteins don't work properly, it can be linked to the development of leukemia that happens as a result of cancer treatments. The most common mutation, seen in 28-38% of patients with t-MDS is abnormal p53 activity, which plays a very important role in DNA repair, and is not so commonly seen in other MDS types like de novo MDS or AML (not related to prior treatments with anti-cancer drugs).
Telomeres are like protective caps at the ends of our chromosomes. These telomers are made up of noncoding DNA and help prevent chromosomes from sticking together or getting damaged. Think of them like the caps on shoelaces that keep them from fraying or tangling. Their role is to maintain the stability and integrity of our chromosomes, which is important for the proper functioning of our cells. Every time a cell in our body divides, the telomeres (which are protective structures at the ends of our chromosomes) get a little bit shorter. This shortening of telomeres happens with each division and over time it can limit the number of divisions a cell can go through before it stops dividing altogether. This process is called cell senescence. Telomere shortening is also connected to genetic instability, which means it can cause changes or abnormalities in our genes.
Analysis of changes in telomere length in serial blood samples from patients who developed t-MDS/AML after autologous hematopoietic cell transplantation (HCT) revealed accelerated telomere shortening in t-MDS/ AML patients when compared with matched controls who did not develop t-MDS/AML.
Studying treatment-related MDS offers valuable insights into leukemia development, and it may be applicable to de-novo MDS and AML in the elderly, which means there are more tools to further our understanding of MDS and AML. Healthcare providers now have a range of effective options, including targeted therapies, immunomodulatory agents, supportive care, and stem cell transplantation. Genetic profiling and personalized medicine further enhance treatment plans. As our understanding of MDS evolves, breakthroughs are expected to provide even better tailored therapies.
REFERENCE:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3437333
https://www.nature.com/articles/s41375-023-01864-6

about the author
Jimena Vicencio
Jimena is an International Medical Graduate and a member of the HealthTree Writing team. She has a passion for languages and is currently learning Japanese. In her free time, she loves playing with her cats. Jimena is also pursuing a bachelor's degree in journalism.
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