Hey everyone and welcome to episode 126 of the Cell & Gene podcast. I'm Erin Harris. For this episode, I'm joined by Dr. Katrina Jameson. She's a board-certified hematologist and a leader in regenerative medicine whose work is reshaping how we detect and treat rare cancers. She serves as professor of medicine at UC San Diego. She's chief of the division of regenerative medicine and director of the Sanford Stem Cell Institute, where her team is focused on tackling cancer at its root. Katrina and I talk about why diseases like myelofibrosis are so often missed in their earliest stages and how new tools such as genomic sequencing are making it possible to catch and intervene much sooner, before these conditions progress into more aggressive cancers like AML.
She shares insights into emerging therapies, from targeted inhibitors to cutting-edge gene editing approaches, and how these advances are moving us closer to truly personalized and even preventative care.
This episode is really worth a listen because of its clear forward-looking perspective on how early detection, precision medicine, and regenerative science are converging to transform outcomes for patients with rare and hard-to-diagnose diseases.
So, here's my conversation with Dr. Katrina Jameson.
Hi, Katrina. Welcome to Cell & Gene, the podcast. It's wonderful to have you on.
It's just great to be here. Thank you so much.
So, I want to talk a little bit about how your team is improving early detection of rare diseases such as primary myelofibrosis, excuse me. What does that mean in practice to identify each zebra's unique stripe pattern? And what I mean by that is I had read somewhere that you were talking about how sometimes hoofbeats are zebras. So if you could give our listeners a little bit of an explanation about what you mean by that, and then how does that actually work into you and your team around myelofibrosis?
Yeah, thanks so much for asking that question. You know, we live in San Diego and we have Safari Park, so we think about zebras more probably than other people, but also we tend to be a hub for seeing people with rare cancers. If you look at cancer, 30% in aggregate are rare. So we shouldn't forget that. When we were taught in medicine, they say, 'Oh, if you hear hoofbeats, think of horses, not zebras.' But it can be a zebra. It can be a rare cancer, a rare diagnosis. And when you look at myelofibrosis, it is a kind of cancer that has the capacity to become acute myeloid leukemia, AML, which has a very short life expectancy. And what we realized with these disorders, they're called myeloproliferative neoplasms, MPNs for short, is that they kind of simmer for a long time and then they just blast off. So what we're trying to understand in the precancerous or premalignant phase is how do we detect it early and how do we intervene to prevent progression to myelofibrosis and AML.
So how do we do that? And that's all about working in interdisciplinary teams here. We live in the land of Illumina, where the sequencing instruments are made. We live in the land of Thermo, where the reagents for science are made. So we can order things in a day and get them. It's very easy for us to be able to do these early detection methods and really roll with the punches as it goes for patients and just say we'll preemptively strike. So that used to be something we would never have thought about when I was a transplanter. I trained as a bone marrow transplanter not once but twice, and I thought the only way to wipe out these diseases was to give somebody else's stem cells to that person so that their whole hematopoietic system, their whole blood system, could be rearranged and improved. But we're learning that that's not the case if we start early in the course of disease.
Excellent. Thank you for that detailed explanation. Now, you did mention MPNs, and I want to talk a little bit about that. So for our listeners who might be a little less familiar, what makes diseases such as primary myelofibrosis so challenging to diagnose and treat, and then how close are we to truly personalized therapies?
I think we're getting very, very close, Erin. You know, what we see with people with myelofibrosis, they have frequently progressed from an antecedent disorder called polycythemia vera or essential thrombocythemia. Fewer people actually just start with that scarring of the bone marrow disease called myelofibrosis; they've usually evolved from PV or ET. So what makes it so hard to detect in the primary myelofibrosis setting is people just have muscle aches, joint pains, they feel a little bit more tired. They're generally people in their 60s. So they think, 'Oh, it's just aging.' And then they start to have night sweats and they go, 'Well, it's hot. You know, we live in San Diego. It's just that.' So there's this strange constellation of symptoms that could just be considered to be aging-related or you worked out too much. But when you put them all together, they become very reliably kind of stereotypical for myelofibrosis. So then it's a simple blood test.
Do you have a mutation in a gene called JAK2, another gene called MPL, or another gene called calreticulin? With those three gene mutations, they make up the majority of people who have myelofibrosis. Now, that's a simple blood test for us. So the community practitioner just needs to think about it. You know, they just need to think, 'Wait a minute, could it be a zebra?' And to think that this is five per 100,000 people here in San Diego. They're not as rare as they used to be, or we used to think, because now we have these tests. And now we can do what's called next-generation sequencing and look for all three of these genes, but also other genes that tell us, okay, this is more likely to progress than somebody that just has the one gene mutation.
Yeah. Sure. Exactly. So now you know what you're looking for.
