Indeed VEXAS is a new disease, which actually is an acronym which stands for: VEXAS – the V is for vacuoles, the E is for E1 ubiquitin ligase, and more specifically, UBA1, which is the main gene that is affected, mostly in hematological progenitors and more specifically in myeloid progenitors. And this mutation will grow within these progenitors and lead to a very specific phenotype that only affects men – this is the X in VEXAS, which is X-linked disease...
Indeed VEXAS is a new disease, which actually is an acronym which stands for: VEXAS – the V is for vacuoles, the E is for E1 ubiquitin ligase, and more specifically, UBA1, which is the main gene that is affected, mostly in hematological progenitors and more specifically in myeloid progenitors. And this mutation will grow within these progenitors and lead to a very specific phenotype that only affects men – this is the X in VEXAS, which is X-linked disease. The phenotype is mostly inflammatory, not very specific, but a lot of clinical manifestations such as skin, pulmonary, and head and neck, etc. A lot of organs might be affected by inflammatory manifestations. And this disease is not germline, you are not born with it but this is something you acquire. So the s is for somatic. And usually it’s acquired at the second stage of life, usually, these patients are 60 to 70 years old at the time of diagnosis, or at least the main onset of the first clinical signs of the disease. And the other thing, besides the acronym, is what is associated with the disease, which is very specific and associated with hematological abnormalities and more specifically anemia, which is the main subject of today, because those patients do have very severe anemia. And this is something that we do not yet understand that this specific syndrome, which was discovered three years ago, is associated in about 50 to 60% of the cases with a genuine MDS, myelodysplastic syndrome, and, usually lower-risk MDS. So far, we have not seen so much transformation to AML, suggesting that this UBA1 gene mostly helps drive a drift of the disease through MDS, but is not sufficient to drive full-blown acute myeloid leukemia, which also depict a very interesting fact about this disease and how myelodysplastic syndrome actually might function.