MYD88WT/CXCR4WT cases, on the other hand, show resistance to targeted drugs (i.e., BTK-inhibitors, but also PI3K and mTOR inhibitors) and are characterized by an increased risk of disease transformation to high-grade lymphoma or of developing a therapy-related myelodysplastic syndrome (t-MDS), both leading to a poor OS [61,114,115]. The gene discussed is BTK; the disease is myelodysplastic syndrome.