Q: Is there any equivalent to a leukemia such as chronic lymphocytic leukemia (CLL), which for ten years can be sort of indolent and then move to a devastating blast phase?

A: Yes. But it's a little bit different. The equivalent for indolent lymphomas is that most of them have a tendency, some more than others, to undergo histological transformation to a more aggressive disease. So that reflects clonal evolution, where a clone that gets additional hits. Once these things become tumors or become lymphomas, they become independent of normal regulatory pathways. They have a higher tendency to accumulate and to survive additional hits. And so what happens over time is that when our normal cells get genetic hits, our cells have huge amounts of surveillance pathways to kill those cells. Those cells die. Otherwise, we would be popping up with tumors all the time. Because our genetic code probably gets hit constantly. You know, our body fixes them or the cells commit suicide through the apoptotic pathway. Tumor cells have a much higher tendency of, number one, not transcribing their code correctly. And number two, not committing suicide when the hit happened. So when you have an indolent process, a chronic process, that you have for years and years and years, over time it's just natural that you're going to get clonal evolution. A clone that gets a hit that gives it a proliferative advantage. And something's going to pop up. And that's what happens in CLL when it undergoes a blastic transformation. In any of the lymphomas, they undergo a large cell transformation.