Overview and Historical Perspective of MDS

Transcript:Thomas Prebet, MD, PhD: Myelodysplastic syndrome is a pretty new diagnosis. There are a lot of bone marrow disorders, and maybe myelodysplastic syndrome is one of the syndromes that has just been completely characterized more recently. It’s a group of diseases, in fact, more than a real disease by itself. And it took quite a while to get all the determinants of the disease, all the subgroup types. Basically, we really got to the point where we can call this bone marrow disease, ‘myelodysplastic syndromes,’ probably in the mid-70s, beginning of the 80s. Before that, it’s interesting to know that they were defined as vitamin- and iron-resistant anemia. That’s where the term of refractory anemia comes, meaning refractory to vitamins and to iron. So, it’s quite ironic to see that one of the most important questions in myelodysplastic syndrome is how to get rid of the iron. This is a defining event in initial steps of understanding the disease.

What’s interesting when we discuss about the evolution of the diagnosis of myelodysplastic syndromes is that over the last 20 to 25 years, we’ve evolved from a purely morphologic classification. It was initially just what we saw in the bone marrow that was driving the diagnosis of myelodysplastic syndromes, defining refractory anemia, and refractory anemia with excessive blasts. In the mid-90s, it became a more cytogenetic-based classification, and now classification integrates also genomic factors and mutation as a definition of the disease. Splicing factor mutations such as SF3B1 are beginning to be a classifying, defining event as compared to what it was previously—for example, the presence of ring sideroblasts, which is associated with SF3B1 mutations.

So, that’s the way that basically our classification or understanding of the myelodysplastic syndrome has evolved since the 1970s. With the classification and the evolution in our understanding of the myelodysplastic syndromes, our classification methods and prognostic tools have evolved, too. Initially, factors that were mostly important when we dealt with myelodysplastic syndrome for classification and prognostication were stable cytopenias that we were facing. Was it just anemia, was it anemia plus other cytopenias, such as neutropenia or thrombocytopenia? And too, morphologic features in the bone marrow, with basically the number of blasts that are present in the bone marrow biopsy and the bone marrow aspirate with a cut-off value of initially 30% of bone marrow to differentiate acute myeloid leukemias and myelodysplastic syndrome. Over the last years, that has been put down to only 20% when we switched from the FAB (French-American-British) classification to the WHO (World Health Organization) classification in 2001.

Now, as a classification, as well as a prognosis factor, this morphology still has a lot of importance in defining prognosis of patients, especially with the excessive blasts. But, as I mentioned previously, all the cytogenetics and molecular markers are now maybe the most important aspects of diagnosis and prognostication in myelodysplastic syndromes. For example, the presence of deletion 5q that was initially associated with profound anemia, early onset of myelodysplastic syndromes, female gender, and some specific characteristics of the bone marrow has now been identified as the 5q syndrome. So, that’s a good example to see why the cytogenetics have such an importance, it’s now beginning to be a defining event.

More recently, these monoclonal markers have been integrated in the prognostication and classification—especially for SF3B1, for example—in spliceosome mutation, and now that’s really how we define myelodysplastic syndromes.

Transcript Edited for Clarity