What is classical cytogenetics by karyotyping? How is it done, and what information does it give? How sensitive is it, and when should it be done? So there's different names for karyotyping. One is classical cytogenetics. The other one is metaphase karyotype. What that test is, is we take the myeloma cells in a dish and we stimulate them to divide and when they divide we're able to capture them. And we can see the, under the microscope even, the individual chromosomes. And we can count them and we can look to see if they are abnormal, if they're broken or rearranged in some abnormal way. And so that was the very first test that was used to look at genetics in cancer and in multiple myeloma. One of the most famous ones in cancer was what was called the Philadelphia chromosome because it was discovered in Philadelphia and it was in patients who had chronic myelogenous leukemia and it was subsequently turned out that this chromosome represented a translocation or a joining between chromosome 9 and 21. In multiple myeloma we have similar events and they form the basis for a classification of multiple myeloma. But curiously those translocations in multiple myeloma are very cryptic and they're hard to see in the conventional cytogenetics or metaphase karyotypes. And for those we need to use other tests. When you stimulate the myeloma cells to divide in the dish there's other cells that are besides myeloma cells that are in the bone marrow. And they often divide much more readily than the myeloma cells do. And so as you're looking through all these chromosomes that come from individual cells usually what you're seeing is normal cells. And so you really have to hunt through the slide to identify ones which look like they might be coming from the myeloma. And to do that we look through generally 20. We try and find 20 myeloma cells on the slide and we try and look to see how many abnormalities they have. But honestly it's quite laborious in time and it would be hard to do much more than 20 of those cells. Who examines the myeloma cells under the microscope in karyotyping? Some by a researcher or a hematopathologist, cytogeneticist in the laboratory. And often what happens is it's very hard to get the myeloma cell to actually divide in the dish. And so it looks like the conventional cytogenetics is normal. And really that just means that we couldn't get the myeloma cell to divide and we couldn't analyze it properly. So most of the time when we do this test in myeloma patients it's normal. But that doesn't mean that the myeloma cell is normal. It just means the test failed. Why do you need to examine the cells that are dividing? The reason that cells need to divide is because when they divide they condense their chromatin their chromosomes small enough that they become visible. And we can actually recognize each chromosome based on how big it is and what it looks like. And in a cell which is not dividing it's not possible to do that.