Chronic myelomonocytic leukemia: Recent insights in pathogenesis

Speaker: Eric Solary
Department:
Hematology
Subject: Chronic myelomonocytic leukemia: Recent insights in pathogenesis
Location: Erasmus MC
Date: 19-12-2016          

Eric Solary talked to us about his research in chronic myelomonocytic leukemia (CMML). He discussed new and improved ways to diagnose and treat the disease, as well as a new way to make a better prognosis for patients.

The first way to make a diagnosis easier, is to look at the percentage of different peripheral blood monocytes a patient has. It turns out that in CMML patients more than 94% of their monocytes are classical CD14+ and CD16-, while this is less in healthy individuals. It was shown that demethylating agents could return the normal distribution in CMML patients. Moreover, monocyte phenotype could detect MDS, a disease that usually evolves into CMML.

Secondly, looking at the genetic mutations in patients may also help to diagnose them properly. Three genomic signatures for CMML have been found, of which TET2 was the most frequent mutation, occurring in 60% of the cases. Aside from these three, two TET3 mutations have been found that are associated with the TET2 mutation.

 

seminar-1Figure 1: A chart showing the different mutations in CMML patients

 

Solary’s lab tried to find a better prognostic method for CMML, but unfortunately they were unsuccessful. There are currently many factors that can be used to make a prognosis, but Solary added a new one: ASXL1 mutation. This mutation is also associated with the disease. Unfortunately, this method does not outperform the prognostic methods that are already being used. However, it also did not do any worse, so it is still useful.

Lastly, new ways of treatment were discussed. Hypomethylating agents help restore the healthy phenotype in patients. However, it turned out that this does not rid the patients of the mutations that they have. Furthermore, hypomethylating factors increase miR-150, a microRNA which has a higher expression in non-classical monocytes. Unfortunately, not all patients responded to this treatment. Looking at the baseline DNA methylation of patients could help distinguish responders from non-responders beforehand, making for a more effective treatment.

I found this seminar quite difficult to follow, but I still found it interesting. I was inspired by the fact that there are still new ways of treatment being found for cancer, even very specific types of cancer like in this case. From listening to this seminar I realized it is important to not only look at new ways of treatment, but also for a better diagnosis and prognosis. I think I might someday like to do research in the field of medicine, so it was very interesting to hear what kind of discoveries are made there.

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