Why can patients have either a high or low white blood cell count at diagnosis?

Why can patients have either a high or low white blood cell count at diagnosis? So I've actually worked on this issue for over 15 years. What we know is that there are molecules that make the leukemic cells stick to the bone marrow. One of them is called CXER4 and they prevent leukemic cells to float off into the blood. Now the bone marrow protects leukemic cells from chemotherapy. How do we know that? When we have, let's say, a high white count in the blood, we start treatment. The first cells that get killed are the blood cells. So the white count will go from 50,000, 100,000 to 1,000 maybe in a week. That doesn't mean that the bone marrow has no 1% blasts. There are many more blasts after one week in the marrow usually. And that is mediated by adhesion molecules that keep the leukemic cells in the marrow. So we have developed strategies to block these adhesion molecules and to flush out the leukemic cells into the bloodstream where they are not protected by the what's called microenvironment of the bone marrow. Again, leukemia is a bone marrow disease, not a blood disease. When the cells are in the blood, they are floating around at high speed and they don't have cells to protect them. In the marrow, they're very comfortable in what's called the bone marrow niche. And chemotherapy is much less effective there. So we have worked on strategies to flush them out for many years with some success, not a home run yet. But that is one way to cure leukemia, to change from a complete remission and a relapse to a much deeper remission with MRD negativity that we discussed. So to flush cells out and then we kill them in the blood, which is actually much easier than in the marrow. So the answer to your initial question is not clear. It is probably a different amount of adhesion molecules for some patients in the marrow. So if you haven't, at least four or five known adhesion molecules, if they are highly expressed in the marrow, the cells have difficulties escaping from the marrow. If they are missing or if they are only not marginally functioning, the cells would be flushed out and can be easier detected and also easier killed in circulation.