Hi, I am Dr. Stuart Goldberg, chief of the Division of Leukemia at the John Theurer Cancer Center. I always like talking about chronic myeloid leukemia because it truly is a disease of firsts. It is one of those diseases that has taught us more about hematology and oncology than probably any other disease we see. The disease CML really starts around 1850s with the description of “leuk”= “white” “emia” = “blood”, “leukemia,” where patients who had CML had very high white counts, and their blood looked white, milky. By the 1850s, early chemotherapy, arsenic, was being employed to treat these patients, which actually had some effect in this disease. We also see some of the early uses of clinical radiation, that is splenic radiation, to make our patients feel better, but the monitoring of CML really starts in 1960s with the discovery of the Philadelphia chromosome, the first human chromosome ever linked to a cancer. We do not call the Michigan chromosome and the California chromosome for all these other chromosomal abnormalities that we now see with other cancers, but since this was truly a first, it has a special name. Well, the thought of a chromosome codes for a protein, BCR-ABL, and the BCR-ABL fusion protein again was the first protein ever associated with human cancer. We now know that the BCR-ABL fusion protein is a tyrosine kinase that turns on the cell, and so, we have learned the mechanism of a malignancy by studying this disorder. From the standpoint of treatment, the 70s, 80s, and 90s was the era of bone marrow transplant, and bone marrow transplant really owes its history again to CML. Prior to 2000, the most common reason to have a bone marrow transplant in the United States was CML, and in groundbreaking research, it was found from the International Bone Marrow Transplant Registry that patients with CML who were treated with a transplant from their brother or sister did much better than if they were treated with a twin, showing us the importance of a graft versus tumor effect, again learned in CML. This led to donor lymphocyte infusions, the first of which again were performed in CML, and by harnessing the power of the immune system, it changes the course of transplantation from a brute force high-dose chemotherapy strategy to an immunologic mini-transplant strategy, all from CML research. We then looked at interferon, one of the first biologic therapies, synthesized biologic, that was effective in a human cancer, and not only did interferon work, but it also taught us all about something called biomarkers, which we now take as commonplace in oncology. The fact that we could predict long-term survival by following whether or not the Philadelphia chromosome was suppressed. In fact until recently, the Philadelphia chromosome was the only biomarker that the FDA would use to approve a drug. We did not have to wait to find out if imatinib was going to make people live longer. All we had to do was show that imatinib suppressed the Philadelphia chromosome more than interferon for the FDA to say go ahead you can start using imatinib; so biomarkers, something very important, again learned from CML. And finally, the TKI era, the idea that targeted therapies could actually work, that we could look at a specific cellular pathway and turn that off. Something that was unique to the cancer cell and turning it off rather than old-fashioned chemo which poisoned everything and hope that the cancer cell is weaker than the healthy cell. We exploit now, something that is unique to the cancer cell and turn that off, again first done in CML, and now we have targeted therapies in a lot of other malignancies. So CML is truly a disease of firsts, first human cancer with the cytogenetic abnormality, first human protein causing cancer, one of the first biologics, the first biomarker, first major use of transplantation, and the first major targeted therapy. And so I tell my medical students and some of the people in the labs, pay attention to CML because whenever there is going to be another first, and hopefully, there will be more firsts, it probably will come out of CML research. That is why I love CML so much, plus my patients do pretty well with treatment. For more information about CML, go to ManagingCML.com. Thank you.