What are some shortcomings of the results obtained from a BMB test?

What are some of the shortcomings of the results obtained from a bone marrow biopsy test? And how can these shortcomings be overcome? One of the other things we're finding in myeloma is that because there is this clonal evolution where the myeloma cells can change over time, there's also a spatial consideration. And that is that if the myeloma changes over time, it's possible that whatever the myeloma looks like in the right hip may be a little different than what the myeloma looks like in the left hip. And as a result of that, we get an added complexity that says sampling a single site oftentimes doesn't give you the full picture of all of the genetic variations that might be occurring in that individual's myeloma. That is, different sites might actually have different genetic variations. And as a result, if the genetics is related to how they respond, you may find that the myeloma in the right hip responds really well to therapy, but the variation that the left hip myeloma has may not respond nearly as well. So now we have a problem in that trying to evaluate the tumor, oftentimes physicians will ask for multiple sampling sites so that they get a better look at all of the components that may be occurring in that individual patient. Now there's a new test that comes out, which is one of the clearing areas for myelomas is that even though the myeloma may be present in the bone marrow, some of it sloughs off into the bloodstream. So you can imagine that if you have myelomas at different locations, they'll all kind of slough off into the bloodstream. Now there's not going to be a lot of myeloma cells, particularly early in diagnosis in the blood, but we now have techniques that are so sensitive that you can now take a blood sample and identify the genetic characteristics of the myeloma cells in the bloodstream. And if that's true, you might actually get a better picture of the heterogeneous population that may be located in different sites in the body, but they're all being spilled into the blood so you get this conglomerate look of all the possibilities. You know, the conclusions from that is that we now have techniques that are getting more and more sensitive, even to the point where even in our own laboratory, we can take a myeloma biopsy and we can analyze the genetic characteristics of one cell, which means if I can analyze the characteristics of one cell, I can analyze the characteristics of a hundred different cells. Now I can look at each individual cell and ask, is there a difference in the genetic characteristics from one cell to another in the tumor? And we find those. And in fact, there are some examples where there are characteristics in a small subpopulation of cells that we've identified by these single cell approaches that are hallmarks for cells that are ultimately destined to relapse and become the drug resistant population that comes out. So one of the things that's happened in oncology in general is that our ability to define the individual characteristics of every individual's disease, as well as the individual cells within a tumor in one individual, the technologies have become more and more sensitive so that we have much better capability of really doing a very minute job of defining genetic characteristics of the disease. Should plasma cytomas, solid myeloma tumors, be biopsied in addition to the standard biopsy of the bone marrow? So we did a study where we used imaging to look for solid parts of the myeloma clone and then we put needles in and sequenced them and they can be completely different. And so that is really important information because you might get a response here, then cells from this part will grow to replace all of the bone marrow and then replace the cells down there. That's more pronounced at relapse. It tells you that you should treat disease earlier when it's not so genetically heterogeneous.