INTERVIEW BioM: You have been leading the MLL Munich Leukemia Laboratory for almost 20 years now, working with a team of 370 employees to process over 140,000 blood or bone marrow samples annually. Since its founding, the laboratory has produced more than 2.5 million diagnostic reports and has authored or co-authored over 835 peer-reviewed publications. At the MLL MVZ, the medical care center, more than 5,000 patients are treated each year for diagnostics, therapy, and sec- ond-opinion consultations. These are truly impressive figures. What is your mission with the MLL? Haferlach: Yes, I am surprised myself at how much these numbers have grown over the past 20 years, now that we are in our twentieth year. We founded the practice and the laboratory in combination back in 2005 because we recognized how rapidly medicine was evolving. More than 20 years ago, we realized that the need for advanced diagnostics was continuing to rise, simply because more methods had become available to characterize these diseases, but also because therapies were becom- ing increasingly specific. As more and more patients with these conditions became very treatable, there was a growing need for positive treatment monitoring and relapse diagnostics. That was the driving force behind defining our mission: to offer the best possible, state-of-the-art leukemia diagnostics for every sample we receive, whether blood or bone marrow – with the broadest possible range of routine diag- nostics, always staying cutting-edge. We also aim to drive research forward, which explains the large number of publications we have authored or co-authored over the years. What technological advances have revo- lutionized leukemia diagnostics in recent years, and how has MLL integrated these developments? You could probably describe it initially with two key terms. Diagnostics over the past 20 or 30 years, and especially over the last ten years, has shifted from what we call a phenotype-based approach to a genotype-based approach. What does that mean? 20 or 30 years ago, we mainly described what we could see under the microscope: how cells looked, whether they looked benign or malignant, and what percentage of malignant cells were present in a blood or bone marrow sample. This also applied to chromosomes. And this still applies today to both of these methods, which continue to be crucially important and set crucial directions and serve as key interfaces within our laboratory. But when I speak about the shift to the genotype, I mean the genetic description – not just chromosomal changes but also individual genes, the DNA, the hereditary informa- tion, or altered information within the leukemia cells that we can now analyze. And this shift from a phenotype-based to a genotype-based description of malig- nant diseases is the true revolution we are currently experiencing – one that we are actively shaping with the capabilities we have here at the lab, both in routine diag- nostics and in research. We are continually developing these methods further in the interest of our patients as well. And that's what makes it so incredibly exciting for me and for all of us: we bring together a combi- nation of all these diagnostic methods and the specialists who evaluate them, all work- ing collaboratively within our laboratory. This integrated approach not only makes the work much more fascinating for us but also enables much more comprehensive and accurate diagnostics for the referring physicians and, ultimately, for the patients themselves compared to earlier times. The goal in cancer therapy is very clear: personalized treatment. How does MLL contribute to tailored treatment for leu- kemia? Could you give us some examples of how MLL's research findings have di- rectly improved patients’ lives? Today, we can tailor treatments much more precisely, as we have a much broader range of therapeutic options available than we did ten or twenty years ago. What does this mean for the individual patient? If a malignant disease, such as leukemia or lymphoma, is diagnosed, we can typically within two to five days precisely identify the specific subtype of leukemia or lym- phoma. It is not one type of cancer, not ten different types, when you break it down into the subgroups we can distin- guish today. Based on today's standards, the 2022 WHO classification, in which we were co-authors, we can now distinguish hundreds of different subgroups of leu- kemias and lymphomas. This detailed classification is crucial for diagnosis, but even more importantly, these subgroups have very different prognoses, meaning the likelihood of cure or, unfortunately, relapse, and vastly different therapeutic options. And this is exactly where personal- ized medicine comes in! The more precisely we can describe the disease, down to the genomic level, analyzing 20,000 to 22,000 genes and their mutations, the more accurately we can also select the appro- priate medications today. Once we have selected these medications specifically, i.e. "personally" for each individual patient, it is like having a house key that fits only one specific door, not any other one. Using this lock-and-key principle, we can continue to track the samples and assess whether the therapy remains effective. Unfortunately, sometimes leukemia cells find ways to evade treatment – to "overtake it on the right or left," so to speak. But we can detect that as well. And when that happens, we have alternative therapies available that we can recommend in turn. This means we don't have to continue the therapy that has become ineffective, we avoid unnecessary costs, and most importantly, we spare the patient unnecessary side effects, allowing us to switch to a better and hopefully more successful therapy. It wasn’t that long ago that almost everyone knew someone, or many knew people, who had died of leukemia. At the time, there were not many treatment options. Since then, we’ve seen real quan- tum leaps. Yes, that's true, and that is due in part to the fact that, unlike in what we call solid oncology – meaning tumors such as breast cancer, ovarian cancer, colon cancer, or prostate cancer – we have direct access to leukemia cells through the blood or bone marrow samples we collect. This means we are far ahead when it comes to describing the specific subtypes of leukemia, and in some cases, we are much more precise than what is currently possible for the tumor types just mentioned. And if we can do that today, then we can not only describe and understand leukemias better, but we can also develop therapies more effectively and, as mentioned earlier, track them more precisely. And precisely these quantum leaps are what make it possible BIOTECH IN BAVARIA - REPORT 2024 | 25 45