Latest / EHA Unplugged / Hematology Portraits: Prof Kirsten Grønbæk

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Hematology Portraits: Prof Kirsten Grønbæk · EHA Unplugged

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Greetings and welcome to EHA Unplug, the official podcast
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channel of the European Hematology Association EHA.
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Hello, I am Isabella Rivera, a medical writer for EHA.
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In this series, we are exploring the world of hematology through
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conversations with leading experts in the field.
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Today we are thrilled to have Professor Kirsten Greenbeck, a
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hematologist and researcher from Copenhagen in Denmark.
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She currently holds the position of Full Professor of Hematology
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at the University of Copenhagen. She serves as a consultant
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hematologist at Ricks Hospital, and she leads her own research
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group on translational hematology.
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Welcome and thank you for being with us today.
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Thank you very much. Professor, can you tell us first
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what drew you to hematology? Yeah, that's an interesting
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story because when I graduated, it's very hard to get a job in
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Denmark as a doctor. So one of my friends passed by
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the department of oncology actually, and I got a three
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months locum there. And but during the night shift
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we were also looking after the hematological patients.
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So that's how I got into hematology, because I thought it
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was much more interesting than ecology.
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So I got a job up there with the hematologist and I very quickly
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got a lot of responsibility and what they actually let me work
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with. It was really inspiring and it
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was a very great environment, good ambience, nice people.
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So that meant a lot to me. So at the time you were working
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as a medical doctor, but you're also a researcher?
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Not at that time. When I was a student, it was
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very hard to get into any kind of research.
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I started in the smaller hospital in Denmark and, and
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there was not the big transition for students to do, to do
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research. So, so it was only when I got
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interest in hematology, I realised I also wanted to go in
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more, dig more deep into that and, and I started out doing
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some epidemiology and had to read a lot of patients files.
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It wasn't the most inspiring and type of of, for me at least,
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research. So after I've been reading 2400
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patient files that actually told me that I didn't have the right
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talent for research, I think it was a good incitement actually
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to do something else. This was a time where there were
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not so many opportunities for young doctors to, to learn more
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about hematology. There were some courses
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actually, and it was when I first joined the Hammersmith
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course, I met hematologist from the other end of the country and
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they say, why why don't you come and work with us?
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So that was a good move for me. Our pathologist was quite a
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famous pathologist at the time, lymphoma pathologist.
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So she, she said, well, though, why don't you come and work with
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me? She got me a scholarship for,
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for doing research and I, I quickly, she quickly sent me to
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the Danish Cancer Society that has their own research labs and
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I was supposed to be there one month and I stayed there seven
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years. So this is a fantastic
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environment. Then it was already becoming
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translational because I was on the one side, I had the
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pathology and on the other side, I had the, the basic scientists
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at, at the Danish Cancer Society.
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So, so this was a already then bridging between the clinics
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and, and the basic science, which is what I have been doing
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the whole time and what I, I really think made it much more
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interesting for me. The hematology and, and
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particularly at that time was, was one of the few, I think,
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specialities where you really got into also looking at the
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cells and all this. And I just from the start, when
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I started to, to study, I actually wanted to do cell
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biology. So we had the first common year
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and then I sat next to my one of my very best friends now and,
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and she was going to do medicine.
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So I had an on medicine. So, so this was for me the way
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to combine everything I was always interested in.
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So that was actually very nice. And do you still now treat
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patients? I do both.
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I have a clinical professorship, right.
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So, so in order to do that, you, you need to be a clinician also
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and, and I really enjoy that. I probably see patients 1 1/2
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day per week and that is mainly patients with the MD's, which
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I'm mainly working with now and also hereditary bone marrow
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failures, which I think is a really interesting field as
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well. And I'm getting more and more
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into that. In hematology you can work in so
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many things. You you mentioned that you work
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on MD's, so how did you get into this?
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Why this subject? I actually did my thesis in
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lymphoma, as I said in the Cancer Society and, and, and I
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think lymphoma are really interesting.
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So, so on the research side, I have actually continuously been
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working with lymphoma. But then after you specialized,
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you specialized very late in Denmark.
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And after I specialized there were, this was at the time where
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a societidine became, you know, used and I went to an
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epigenetics meeting in Puerto Rico after my first ES meeting
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about epigenetics. And that was really very
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exciting. And then I opened it for me.
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I actually mostly went there because it was Puerto Rico, to
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be honest. But I got very, I, I got very
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much engaged in epigenetics. And then we're lucky to meet
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people that are really now very famous in epigenetics.
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One of the, I think they now called them the great
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grandfathers of epigenetics. I'm still working with them in
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Stand Up to Cancer, Epigenetics Dream Team, Peter Johnson and
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Steve Bailey. And this was really good for me
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to get into. I feel that it's very exciting
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because that was when we knew we first figured out that
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epigenetics was so important in cancer.
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So, so, so that's sort of my way into MD's because we then
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started with a societdine and, and then there was a position in
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that part of the department of a permanent position.
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So, so this is sort of why I left lymphoma a little bit in
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the clinics and moved to MD's. I think this is the most
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interesting subject you can take because there's still so much we
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don't know about MD's. There's still so much to learn.
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I mean, with a lot of the other diseases, there's so many good
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drugs that work very well with MD's.
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We're still there. I mean, we could transplant,
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yes, then we can cure. But if we don't transplant, we
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don't have so much to offer. Unfortunately.
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There, there are new drugs coming up and and we can make
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lives better. We can extend lives maybe.
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But you know, cure is far away still unless you transplant.
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So, so it is a challenging disease and I think we now over
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the last 10 years have got to know much more about the biology
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also, which I I find very interesting.
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This is a way forward, I think. Yeah, yeah.
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And why is epigenetics important in.
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In general. Well in well in MD's.
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That's a good question because we don't really don't know why
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isocytidine works still after all these years.
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But isocytidine, which is a hypomethylating agent was the
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first drug to ever show a survival benefit in, in high
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risk MD's. So, so this is sort of of how
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that came in. I did my thesis and then it was
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discovered, of course, the, the relationship between the, the
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epigenetic regulators to two DMT 3A and A61 and, and, and, and,
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and the, the changes both in, in DNA methylation and, and, and
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chromatin modifications. And, and I think since these
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mutations are so abundant in MD's, of course, this is also
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the epigenetic changes are, are huge.
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And we have been working with that a lot in, in the lab 10
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years ago, it was discovered that that this starts at the
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very, very early time point, long before people get sick,
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probably, you know, with blowing hematopoiesis.
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And, and one of the things that we did in our lab were was to
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look at, so those individuals who had these mutations that
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CHIP mutations and actually otherwise do not have changes in
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blood cells or, or, or or other kinds of hematological disease.
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They already at that stage have certain epigenetic changes if
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they have tattoo mutations at the enhancers.
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So, so meaning that is probably what drives the disease towards
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a, a myeloid malignancy. And I think, you know, so yes,
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epigenetic certainly is very important for, for this disease,
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but I, I think it's important for many other diseases assisted
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in that genetics and it's all interlinked.
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And I think that whole discovery has been done while I, I've been
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around. So I mean, I didn't do it on
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this, but we were all thinking that, you know, in the
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beginning, we all think there must be some genetics behind
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this, these epigenetic changes and, and there were.
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So that's why you're working now on is the genetic basis of this
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epigenetic what I'm seeing? Yes, yes.
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Well, I'll be working on both things.
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I mean, it's because it's all interlinked.
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You can't look at, I mean, I think you can't really look at
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one thing without looking at the other.
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It's, it's all, I mean, also with the abilities we haven't, I
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mean, remember when I was doing my thesis, it took a year to
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analyse the gene. We were doing what was called
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GGG gels. So you did do all these gels,
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you know, you could change them three times a day And, and it
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was a huge amount of work. And nowadays, you know, we put
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it into a machine and you or you send it somewhere and somebody
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else analyse to get the data. So nowadays the most important
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thing is actually how to handle the data because it's, it's,
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it's very automatic. And, and of course, I think we
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all understand that now that, that that one thing does not
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exist without the other. It's you, you have to look at
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the whole picture. So you.
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Talked about clonal hip and anthropoiesis.
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Can you say briefly what this is and where you have been lately?
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Like it's a, we are currently interested in this before we
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knew it existed because because I came from the lymphoma field
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and and then went to MD's and we had quite a few patients where
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we could see they had both diseases, not not necessarily
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one occurring after treatment of the other, but but occurring at
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the same time indicating that there must be a common
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background. So we were really speculating a
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lot about that back in 2910, I think.
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And and then it was discovered of course that some of these
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mutations in stem cells occur at a very late early time point.
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And of course, if you have a mutation in a very early stem
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cell that that that gives this cell a growth advantage and, and
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it differentiated can, you can actually probably sometimes go
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in both directions. So, so, so, so this was the way
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we, I started thinking about this.
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Now we know that most genes are associated with in, in
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clonhematoporesis are associated with, with development of
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myeloid diseases. On the other hand, that if you
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have the structural aberrations, if you have that in, in, in
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scenario, it's more common to develop lymphoid diseases.
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So, so, so this whole background, you know, of where
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things come from, I think has been super exciting.
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And, and This is why we had digged into that.
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And, and I think because we were already thinking of it before
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somebody else figure it out. We quickly went into the field
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and also had material both from lymphoma and, and, and myeloid
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disease and could, could look for some like clone
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hematopoiesis in, in, in lymphoid cancers for me, for
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somebody with a, a split brain where you on the one side had
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lymphoma background and now went into the to the myeloid field.
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I think it was a very very, very interesting.
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Sorry for me to look. You understand the common
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origin? Yeah, in some cases.
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Yeah, in some cases, yeah, yeah, and, and, and, but also how, how
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these thing may be influencing each other.
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So it's it, it's so you do have a higher risk of of of lymphoid
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disease if you have slow hematocritis, for example.
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When you have clonal hematopoiesis at the beginning,
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you don't know it, no, And the doctor doesn't know it because
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it's not something that gives you.
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No, but it's very common. Yeah, yeah, yeah, it's there,
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but. It gives you a predisposition to
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develop cancer, but nobody will detect it because will you will
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not go look for it. So how do you work on something
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like that? Because you have to find the
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people who have it and trace their history.
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This is a big discussion point because there are these people
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that I have have ready to predisposition to cancer.
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This is a different story. So this occurs during lifetime
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actually, if we use very sensitive methods, these clones
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can be detected in almost all of us.
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But after the age of 60, it becomes very common.
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And, and, and there's an, an arbitrary limit if you have to
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have a, a 2% variant of lead frequency in order to call it
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clone limit crisis. But after the age of 60, it's
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around 10%. And then it increases by age
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that you get more and more of these clones.
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But you can walk around happily with these clones and, and, and,
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and the, IT has been shown that this associates, it's quite a
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lot of different diseases, but, but the risk of developing
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hematological cancer is less than 1% per year.
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So, so it's not that at least for the moment that we that we
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do population screening to say this and that person have this
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predisposition or what you could say.
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Because I mean, the, the risk is also that we make a lot of
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healthy individuals sick. And as long as we do not have
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anything to offer for them, I think we should let people be
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happy with their mutation. Yeah, the right not to know.
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But of course there are some signs that that now there is a
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risk of this getting more in the direction of myeloid cancer, for
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example. And this is when when they
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become cytopenic. So if they have anemia and
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particularly if they have anemia and one additional cytopenia and
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then the mutations, then then they are on the road to develop
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develop bilio cancer. And that's the condition we call
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clonocytopenia from the term significance, which is much more
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likely than chip to to to end up being a myelo cancer.
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But there are now prediction tools so, so that you can
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actually plot in the mutation that you find in this patient
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and and other things and then a biochemically the chemistry,
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etcetera. And then you you can can predict
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whether this person is going to develop myeloid cancer.
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But I don't think we are the states where we should do that
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at the population level. Let's change gears a bit.
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What can you tell us about your involvement with EHA?
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So first, what's your first memory of EHA?
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My very first memory of ESA is the very first ESA meeting where
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I had a poster. There was a research I did in
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that smaller hospital, I think. And then I was certainly
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travelling with the company because otherwise I had no money
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to go to heat. So yes.
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So, so it was a different time for me, but there was a, a great
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experience to be at, at the well, it was a relatively small
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Congress at the time actually. But, but, but for me, it was
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very exciting to, to hear all this science and meet all these
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people. Well, it wasn't so, you know, I
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was quite shy. And how did this evolve?
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How did you become actively involved in the?
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It took a long time actually. So as I said, at that time there
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was nothing called lightning the flame.
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There was nothing like young you'd say.
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I did actually know people that were very much involved in the
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ETA. But you know, I wasn't a big
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name at the time. I was not really getting
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involved or not asked to be involved in a way or there
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wasn't opportunities as there is now.
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I think for also people on on on their way in their careers.
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And I think that's something we've been very good at changing
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in the ETA. So you actually had to be a big
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name almost to be into USA in the beginning.
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And this is absolutely not like that now.
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I think everybody can contribute in some way.
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And this is also how you you get on.
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And you say, so it was only when I applied to become a professor.
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So it's quite late in my life. The late David Grimwaite, who
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was he very what's involved in USA was evaluating my
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professorship. So he called back and said, we
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need this, this girl, she needs to go into the SPC and the
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scientific programme committee. So this my, was my way in there
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was a great opportunity. First of all, I like the work
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there. I really like the people a lot
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in the committee. We had a lot of fun and, and,
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and, and, and you got to see a lot of different kinds of, of
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research and, and, and I was like, oh, who am I to evaluate
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this? You know, but, but, but then you
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have all, the, all the conversation with the other
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members, you know, that are in, in your part of the, the
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evaluation committee. And, and I think I learnt such a
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lot about from that. And I met, you know, I think
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what have made me stay so close to you say is the staff at the
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offices. I mean, we had such a lot of fun
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always. And I think that that make it, I
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mean, and not not only fun, but also extremely good support.
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And I think that communication that you feel you're part of a a
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community, I think that was all family.
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That was really important for me.
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And so how has this impacted your career?
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I think it has impacted me in the way that I got a much larger
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network of, of, of, of people. I mean, you, it's a way to get
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to know people working not only in your own field actually, but
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also in, in, in other fields. And I, I think that's important
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because you get, you get different kinds of input, that
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research environments are different and, and you can learn
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from each other. I think that that's important.
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I was four years in, in the SPC, as you should, and then rotated
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off and then somebody, I don't know who suggested me to, to the
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board and then I got elected. I was very surprised, actually.
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So, so, so I remember I asked Elizabeth McIntyre because I
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knew her from the SPC. So, So what are we actually
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doing here? So, and then little by little I
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got into it and I and I really enjoyed the work.
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So yeah, everything I've been doing is by chance is not a lot
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of it that has been planned. And I think I always say I'm the
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happy #2 and, and I actually think I am.
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There was this joke about the Danes.
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You know, they, they were the happiest people in the world.
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And that was because they had so low expectation.
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I, I'm not sure that's correct because of course we have high
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expectations. But but I think in a way, you
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know, this is this has been important to sort of, you know,
18:47
not not set too high goals because then you're deemed to
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fail. But we also have something
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that's not so good in Denmark called the Yandolo, meaning you
18:56
shouldn't think you are somebody and that sometimes take over too
18:59
much. So, looking back at all of
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these, what have been the most rewarding moments of your career
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so far? Oh, the most rewarding, it's
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probably not a moment, it's a process I would say.
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But for me, the most rewarding thing is to have students and,
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and see them grow. I have been so lucky.
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It's all about picking the right people to your lap.
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And, and then I think what I experienced at the Danes Cancer
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Society was this very vibrant environment where you didn't
19:31
want to go home because it was nice to work with the other
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people. And so you just work late at
19:35
night and, and I'm, I've been working, I think, I think for me
19:40
to see the group working together, functioning and, and,
19:43
and, and, and, and supporting, and the students supporting each
19:46
other and supporting each other's career.
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And the most rewarding thing for me is to to see them, yeah, be
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successful. So what advice would you give a
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young medical doctor that is now considering which speciality to
20:06
go into? Ad of course, as you go into
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himmatology, that's, that's clear.
20:11
It's the most exciting speciality, I think.
20:14
And then I think also, I think they need to make up their minds
20:19
if they want to do research. I, I, I feel now it's a little
20:23
bit different with the generation we have now.
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I think they have a different way of looking at the work life
20:29
balance And, and definitely, if you go into research, forget
20:34
about the seven hours a day work five days a week.
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It's a lifestyle. And if you like that lifestyle,
20:45
go for it. But you have, you have to
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consider where you really want to invest your time.
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For me, it's been super rewarding.
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I, I think it's been, I didn't expect anything like this at
20:56
all. So, so it's been a big, a great,
20:59
a great journey. And I think I would recommend
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anybody with the interest to do it, but but don't expect it to
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be. I mean, it's it's also a hard
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job. Yeah, it's a fun, but a hard.
21:11
Job Thank you very much Professor Koenbeck for sharing
21:16
your life with us and for your expertise and all your
21:20
experiences and to all of you for tuning in to EHA on plot if
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