: Okay, well obviously the first thing is that my parents were very encouraging of me in any kind of intellectual activity. My mother always hoped that I would be a doctor. The critical component was my getting a scholarship to the University of Chicago four-year college when I was a junior in high school. This is the so-called Hutchins College.
Collins: Oh, oh.
Rowley: We were really treated as though we were college students, even though we were sixteen and seventeen and given a great deal of responsibility and dealt with as adults. It was an important experience for me because we were taught to question and to read primary materials not just what you’d see in a textbook. So we had almost no textbooks to study.
Collins: Yes. You were probably surrounded by a group of pretty bright peers as well.
Rowley: Absolutely. We were a class of sixty-five. So we weren’t very big, and we were separated from the standard University of Chicago college. Everyone was both smart and motivated and the teachers were outstanding. So that was important.
I found, as I took college biology classes that I enjoyed them. Initially I was going to go into physiology because that seemed to me to be such a dynamic field.
Rowley: This was back in 1942. But all of my lab mates were pre-med. So I decided well I might just as well be pre-med along with them.
Collins: And make your mother happy.
Rowley: That’s right. So then I applied to medical school and the quota for women was filled, because it was three women out of a class of sixty-five.
Collins: And that was all they wanted?
Rowley: That’s right. And they’d already selected their three, so I had to wait nine months.
Collins: Oh, my God.
Rowley: But since I was only nineteen at the time, it wasn’t a great tragedy. So I started medical school at age twenty in 1945. I enjoyed medicine, and I always intended to be a clinician, but also, because I was married the day after I graduated from medical school, I intended to do medicine only part-time, because I wanted to take care of my family.
Rowley: I ultimately had four sons. I worked, therefore, part-time in well-baby clinics and then began working at a clinic for retarded children. I was working in that clinic in the late fifties when Jerome Lejeune discovered that Down Syndrome was trisomy for chromosome twenty-one.
Part 2: A Transition from the Clinic to the Laboratory
After practicing medicine in children’s clinics, Dr. Rowley traveled to Europe on an NIH fellowship. Here she describes this early research experience, and talks about her decision to continue her efforts in the United States. She also explains the rather unusual circumstances surrounding her initial research at the University of Chicago.
Rowley: My husband was going to Oxford to work with Lord Florey. So I applied for a special NIH fellowship, which allowed me training in Europe. I worked with Laszlo Lajtha and Marco Fracarro and learned cytogenetics in Oxford.
Collins: Now, was that your first foray into research?
Rowley: Really, it was. I did some research after I graduated from medical school because my husband was behind me in school. That was really pretty minor. But I worked with Laszlo Lajtha on the pattern of DNA synthesis in chromosomes. That was just at the time when people became aware of the late labeling “X” chromosome.
Rowley: At this time, working with Laszlo, we didn’t know about any of the work of say Jim German or Grumbach or others. I could go to Sweden and get material from Jon Lindsten on patients with abnormal “X” chromosomes, including four “X’s” and a “Y” and ring “X’s”, etc.
Rowley: I did autoradiography on this material, and we showed that in all of those patients with abnormal “X’s”, all of the “X’s” except for one were late labeling, therefore, presumably inactive. In cells with structurally abnormal “X’s” they were preferentially late labeling as compared with the normal “X”. Of course you have to recall that back in 1960 we couldn’t tell the “X” chromosome in the karyotype.
Rowley: It was clear that there was one “C” group chromosome, as they were called then, that was late labeling.
Collins: Yes. What was that like Janet? You had been primarily doing clinical work.
Collins: For almost a decade, I guess.
Rowley: Three days a week.
Collins: And then suddenly you’re put into a very different environment. Not only in terms of doing research instead of clinical work, but being over in Europe. It must have been quite a transition. Was that exhilarating? Was it a little unsettling? What was that like?
Rowley: Oh no. It was very exhilarating. I really enjoyed it and the challenge of trying to figure out what chromosome was involved, particularly when there was this one late labeling chromosome in female cells. I used myself as the donor of the peripheral blood.
Collins: Oh, in the long tradition of self-experimentation.
Rowley: That’s right. So then I used somebody, I don’t remember whom, who was a male and didn’t have an obviously very late chromosome, using tritiated thymidine. It was through Marco Fracarro, who was a good friend of Jon Lindsten that we knew of all these patients with abnormal “X’s”. Jon arranged to get blood on all of these patients when I came over to Sweden. I added the tritiated thymidine and then went home with the slides.
I got so excited about what I was doing, that when I came back to Chicago after the equivalent of a year sabbatical, it was clear to me that I didn’t want to go back to the clinic. I then approached Dr. Leon Jacobson, who was head of a DOE-funded large institute here at the University of Chicago, about the possibility of continuing my research.
It’s very important and instructive, that I approached Dr. Jacobson, in the sense, very naively.
Rowley: Because I had no credentials, none whatsoever. And I asked him: A. Would he give me a job and pay me to work three days a week? Secondly, would he give me lab space so I could keep on studying all these slides that I’d made in Europe of these abnormal “X” chromosomes.
Rowley: And Dr. Jacobson did that.
Collins: Boy that’s remarkable. How likely would it be today?
Rowley: Not at all.
Rowley: I mean I had a nice paper in “Nature” that I’d written with Laszlo and other people on the abnormal “X’s” and the labeling pattern. But that was a single paper and obviously coming out of a supportive environment. What was I going to do on my own when nobody at the university was doing anything like that?
Collins: That’s amazing.
Rowley: But Dr. Jacobson, whom I had known as a professor when I was a medical student here, did have resources. I got five thousand a year salary. I had no technician, but I could use the microscope and do the work myself.
He actually supported me all the time that I was here through this DOE Institute. It was really almost ten years before I did anything that was noteworthy. Certainly it was six before much started coming out that would even catch anybody’s attention. But he was very supportive right through that period of time.
Collins: Sounds like he was one of your heroes then, in terms of giving you a chance.
Rowley: Absolutely. Absolutely.
Part 3: An Interest in Leukemia
As her research at both the University of Chicago and Oxford progressed, Dr. Rowley became interested in the study of genetics as it relates to leukemia. Here she describes some of her early work in that field.
Collins: So how did you get interested in the side of genetics as it relates to leukemia?
Rowley: Well, Dr. Jacobson was a hematologist.
Rowley: Actually he was a member of the National Academy because he was one of the people who proposed that there was a substance, erythropoietin, that led to a lot of the work of Gene Goldwasser, who was a colleague of his. So, I was in the section of hematology and oncology. So, my laboratory was in hematology.
Rowley: And every so often Dr. Jacobson would have a patient who would have CML, and he’d want to see whether the Philadelphia Chromosome was present. So, while I was continuing and extending studies on the pattern of labeling of some of the other chromosomes, I would do a cytogenetic analysis for him. Then, as my own research in labeling patterns of chromosomes came to an end, there were all these interesting patients. Particularly those with what was then called pre-leukemia.
Rowley: So I started studying their chromosomes and I found that some of them had gains of chromosomes and some of them had losses of chromosomes. But again, in the sixties it was not possible to tell whether they were the same chromosome or different chromosomes, etc.
Rowley: And then my husband took a second sabbatical 1970-71, again in Oxford at the Dunn School.
Rowley: I arranged to work with Walter Bodmer. It was just when Walter went back to England to become the Professor of Genetics at Oxford, in 1970. In fact, the laboratory was gutted and being renovated. So I did my research work up at an MRC Unit with Peter Pearson.
Rowley: And that was just when banding was coming in and Peter had a fluorescence microscope, so I could go over at night and work on his fluorescence microscope. What I was studying then were some of the cells and cell lines that Walter and Marcus Nabholz were using for gene mapping.
Rowley: I showed that there were major rearrangements in NIH 3T3 cells. I also showed the association of dense hetero-chromatic regions using the technique of Gall and Pardue with the dull staining regions on quinacrine fluorescence. I could do the equivalent of “C” banding and “Q” banding on the same cells.
Collins: Oh, that was what you needed the fluorescent scope for was the “Q” banding.
Rowley: That’s right. Because I had the naive notion again that I was going to map them, karyotype the cells, and track through all the rearrangements in the NIH 3T3 cells. Fortunately I discarded that idea right away. But I was using that technique also to identify the human chromosomes in the hybrids based on their fluorescent banding pattern.
Rowley: I worked on that project, and I didn’t do any work on human leukemia in Oxford. I did analyze material from patients whom I studied who appeared to have only forty-five chromosomes. They were male patients, and it wasn’t clear whether they were missing a “Y” chromosome or not. In fact, using Peter’s scope, I could show that they were all missing a “Y”.
Rowley: So, a paper came out in “The British Journal of Hematology,” I guess in 1971, just showing that the chromosome that was missing in these older males was the “Y”. This was one of the first studies of leukemia cells using bonding.
Part 4: An Exciting Discovery
Here, Dr. Rowley explains the process of confirming the first two translocations she discovered, and how these discoveries led to more complicated research.
Rowley: I came back to the university, and again, Dr. Jacobson helped find the resources for me to buy a fluorescence microscope.
Collins: Which were not widely available to a lot of people at that point.
Rowley: That’s right. So I got my fluorescence microscope in 1972.
Rowley: And then I started looking at material that we had on various of our leukemia patients, particularly because I was interested in this question of the gain and loss of chromosomes and trying to define whether they were the same or different chromosomes.
Rowley: I also looked at patients with some chromosome rearrangements. In the first group I looked at, were patients who I showed had an 8;21 translocation. That was the first translocation I discovered–probably June/July of 1972.
Collins: I didn’t realize that that was the first one you were sure of and…
Rowley: That’s right…
Collins: That depended on the “Q” banding to be sure you had the right partners?
Rowley: Absolutely. Because previously in the literature based on standard banding, they were called minus “C,” minus “G,” plus “D,” plus “E.”
Rowley: That was because a piece of chromosome 8 was moved to 21.
Rowley: So 21 looked like a “D,” and the 8 looked like a 16.
Collins: I got it. Was it realized up until then that this was actually a balanced rearrangement? Or was the perception that was much more complicated?
Rowley: It wasn’t clear.
Rowley: Actually, I think Eric Engel proposed that maybe it was a translocation before.
Collins: But nobody was sure.
Rowley: It was not clear. So I first looked at one patient with “Q” banding, and then I had a second patient with this abnormality. I sent a letter to the “New England Journal of Medicine,” and they rejected it.
Collins: That wasn’t interesting?
Rowley: I sent it to “The Annales de Genetique”; Jean DeGrouchy was a good friend of mine, and he was editor. It’s apparently the most cited paper in the journal.
Collins: That’s fascinating. Now, was it well received? Or did people not believe it? Or?
Rowley: Well, I think it was just sort of “so what.” And that’s why everybody focuses on the Philadelphia Chromosome. And again, what I was looking for in patients who were in blast crisis, because they had very complicated karyotypes, was to identify what appeared to be extra “C” group chromosomes.
So, I was paying attention to trying to identify whether the “C” group chromosomes were the same and looking carefully at all the chromosomes. I noticed that one chromosome, 9, was too long and had this long piece of pale material at the end of it.
Collins: Again the “Q” banding told you that was a 9.
Rowley: That’s right. None of this could have happened without banding.
Rowley: Banding was absolutely critical. I had cytogenetic material in the chronic phase from some of these patients when they were only Philadelphia positive, and again, the 9 had the long piece of material on it. So I decided that in fact the piece from 22 wasn’t missing but that this was another example of the translocation. I sent a paper to “Nature,” and after the usual sort of delay, it got published in “Nature” in 1973.
Collins: So what did that sort of experience feel like? People are always interested in knowing, what was the moment like? Either for the 8;21 or the 9;22. When you were sure that you had understood something that people hadn’t been clear about before. That this really was a balanced translocation. You knew what the partners were. Is that something that sort of came as a flash one afternoon? Or was it over a course of time, building up the evidence and convincing yourself?
Rowley: Once I saw it in the chronic phase, and I saw it in three or four patients, I went back and got peripheral blood on these patients and could show they had a normal karyotype. Thus this wasn’t some rare congenital translocation.
Rowley: I have to say I was very excited, but I was very perplexed. Because clearly translocations had been found before, and they were obviously known as a cause of Down Syndrome.
Rowley: If you have a 14;21 translocation in a parent, then you have a risk of Down Syndrome. But I kept trying to figure out whether there was any precedence for this, and so I talked with a number of colleagues at the University of Chicago as well as Barbara McClintock, about what could break and rearrange two chromosomes so precisely.
Rowley: I never got a satisfactory answer. In fact you can say there is no satisfactory answer now.
Collins: You could say that.
Rowley: That is because we don’t know the mechanisms for translocations, but at least of course now we know the….
Rowley: That’s right and the genes that are involved. Not too long after that I discovered the 15;17 translocation in acute promyelocytic leukemia. I also showed that the gains and the losses of chromosomes in other patients were nonrandom and often involved the same chromosomes. I became a believer that chromosome abnormalities in leukemia cells were central to the development of the malignant process.
Collins: Did you have a hypothesis in your mind at that point about how that might work? About how such recurrent translocations might play a positive role in the leukemic process?
Rowley: Well in the sense of a kind of sophisticated understanding we have now, the answer has to be no. All I knew was that these were critically important because every patient with APL has a 15;17 translocation.
Rowley: And therefore it had to be central. Thinking of two genes being broken and fused, I have to say, that certainly didn’t occur to me. But it was clear that there were some critical genetic events that were the same in the same translocation. That I certainly believed in. So I’d go to hematology meetings. They had education sessions on Sunday morning, and I would just preach to these people that chromosomes were important and you as hematologists have to pay attention to them. Not too long after, in 1978, we found the 14;18 translocation in follicular lymphoma.
Rowley: So recurring translocations were occurring in lymphomas as well as in leukemias, thus they were a central part of malignant transformation.
Collins: I guess at the time it would have been very difficult to imagine the precision of these rearrangements would turn out to be what it is. That these breaks, which under the microscope appear to be similar, would even when you got to the molecular level, be so closely spaced together in terms of the exact location of the break points–often times in the same intron of two different genes that would then have to be stitched together in a very precise way. I think…it would have been difficult for anybody to imagine that was going to be the outcome, and it sounds like that was not on a lot of people’s minds.
Rowley: I don’t think it was. The first translocation that was cloned was Burkitt lymphoma, and, in fact, the breaks are quite variable. They occur within the immunoglobulin gene, but as far as MYC is concerned, they can occur five prime, three prime of the gene.
Rowley: The translocation does not lead to a fusion protein. Rather, it leads to the abnormal expression of a normal MYC protein.
Rowley: The same is true for BCL 2.
Rowley: If you had asked scientists, even very very sophisticated, thoughtful people, back in the late 1970’s, I don’t think anybody would have imagined that there would be fusion genes. That would have not have been on anybody’s mind.
Part 5: Molecular Cytogenetics: Its Present and Future
Dr. Rowley began a laboratory dedicated to research into molecular genetics. Here, she explains the challenges associated with such a laboratory, and gives her thoughts on the future of molecular cytogenetic research.
Collins: Yes, yes. Who would have thought it? Well then you went on from there to actually identify the molecular level. The partners. And a significant number of these rearrangements that you had first described. So this must be a fairly satisfying span of experimental effort going from the initial observation to now saying at the molecular level exactly what the deal is. Reflect on that for a minute here, what it’s like to have that kind of perspective?
Rowley: I’m overjoyed at how all of this has worked out. I’m especially pleased that what we’ve managed to do is to co-opt outstanding scientists, including yourself through Paul Liu, into being interested in chromosome translocations and in cloning them and trying to figure out what the genes do. For such a long time, cytogenetics was considered by a number of eminent people as just so much stamp collecting. It is very rewarding. I did know from the late 1970’s that trying to identify what was going on was critical. And back then, of course, the techniques were pretty primitive. My own notion was to work with Tony Carrano to use chromosome separation in CML so that you could isolate the Philadelphia Chromosome and probably some chromosomal fragments. Maybe with techniques that were available then, you might be able to identify the Philadelphia Chromosome and the genes on 9 and 22. Obviously, with new techniques there were better ways to approach this.
Rowley: It took me three years to be able to get the resources, and the space, and a person to come and work in the laboratory to do molecular genetics.
Collins: Yes. That’s quite a transition.
Rowley: At this point I felt that I was not in a position to become a molecular geneticist. After all I was more than fifty years old or some such. So it was a matter of recruiting somebody who could come and develop this program. Then Manuel Diaz came and started the molecular genetics laboratory. During the next fifteen years we’ve been able to recruit many different people, who’ve come and worked on cloning a number of these translocation break points.
Collins: And having visited your lab, I can certainly vouch for the fact that you were a lot more than just an overseer of the molecular efforts. You’ve got yourself very much involved. Don’t sell yourself too short.
Rowley: Well that’s true, but I had very dedicated teachers. Very patient teachers as well. But I was not satisfied with just sitting back and finding the translocations and letting somebody else have the fun.
Collins: Yes. Yes. Well that’s very clearly not the mode that you took. Where do you think this is all needing to go next in the future, as we sort of stand here at almost the turn of the century looking at the remarkable strides that have happened in molecular cytogenetics–a field which didn’t exist thirty or forty years ago. Through the efforts largely of yourself and others…a small number of people has become this very exciting, rapidly moving field. Where’s it going next?
Rowley: I think there are at least two major unanswered questions. One is what causes chromosome translocations? We and others are trying to study that. We’re using the fact that unfortunately some patients with cancer, anywhere from one to fifteen percent, who are given high doses of drugs that inhibit the function of topoisomerese II, will get secondary acute leukemia.
Rowley: And in these patients a gene that we identified, as well as others, the MLL gene at chromosome 11 band q23, is very frequently involved in the leukemia.
That gives us a clue to look for things like topo II sensitive sites within this gene to see whether that might play a role in the translocations. In fact, we and others have evidence that in fact there is an in vivo topo II cleavage site, which we’ve mapped as being the general location of the breaks. We don’t have it down to the nucleotide level, but there is also a DNAse I hypersensitive site.
Rowley: The other interesting fact is that if you look at infants who also have MLL translocations, they have breaks near to this topo II cleavage site.
Rowley: The breaks are often up to several kilobases away from the topo II cleavage site, so I don’t want to make it sound too specific. But there is some tantalizing evidence that maybe we can begin to figure out what causes translocations.
The second major goal, and this of course is dear to me as a physician, is trying to figure out how we can develop genotype-specific therapy.
Rowley: You can say that it was developed for acute promyelocytic leukemia, in a sense by accident, because it was the Chinese who were experimenting with various drugs, who found that all transretinoic acid, specifically induced remissions in patients with APL. When it was discovered that retinoic acid receptor alpha was one of the genes involved in the translocation, that made some sense.
We need the same kind of genotype-specific therapy for all the other translocations.
Rowley: Again, naively, I once thought that antisense therapy would be effective, or ribozymes. But it’s clearly much more complicated than that.
Collins: What do you thing the chances are that we will make real strides in that area, the genotype specific therapies in the next decade? Are we perched on the brink of that becoming a reality? Or is this going to be a long hard slog?
Rowley: Well, I think ten years is probably too optimistic.
Rowley: Again, scientists are working on an area about which I don’t know a whole lot, but I do know that you can intercalate a third strand of DNA in the double helix and that this can somehow perturb the replication and the function of the target gene.
Given how quickly one can actually do genome sequencing, it would not be a problem to get the exact DNA sequence at the site of a translocation break point in an individual patient. If you could really get a third strand of DNA somehow specifically intercalated at that translocation junction and have it bind to the DNA, so first it can’t be expressed but second, the cells can’t replicate, that could be the type of genotype specific therapy that might be effective.
Rowley: The other approach we thought of was the fact that the BCR ABL fusion protein is a unique protein in these cells.
Rowley: Could you target it with antibodies? But I think that many of these fusion proteins are not expressed on the surface of the cells. So then you’re going to have to figure out, how can you target a fusion protein that may be intercellular?
Collins: Right. Or maybe internuclear as many of them seem to be.
Rowley: That’s right. So I think those are things to work hard on in the future.
Collins: But they’re not right around the corner.
Rowley: That’s right.
Part 6: Taking the Long View in Life
Dr. Rowley talks about the importance of balance between work and family. Working only part time when her children were young allowed a rich family life; patience and persistence made up the difference in the lab.
Collins: Well that’s a very interesting tale you’re telling of your own career over these decades of discovery. Who would you say, if you had to pick out, have been your own heroes? Sort of scientific examples of people that you’ve admired and then strove to sort of chart your own course in a similar way?
Rowley: Well, I had the advantage both as a medical student and then coming back on the faculty at the University, of knowing Dr. Charles Huggins fairly well.
Rowley: He was somebody who really continued to do research up into his nineties. So he was certainly a very important role model. I have to also give my husband credit. He’s an experimental immunologist still at age seventy-five, working in the laboratory on projects and injecting mice and the rest of it. His single-minded focus on research issues and questions and how to approach them best has been a very good model for me as well.
Collins: I guess I should also ask you, Janet, if you would have things to say to young scientists, maybe particularly to young female scientists, about the challenges of trying to combine many aspects of a productive life in terms of research and some clinical medicine that you have done quite a bit of, and family, which obviously was very important to you. I know you have had a remarkable family that’s arisen from you and your husband’s dedication to that part of your lives too. Is that something you’ve found relatively easy to balance–all these responsibilities? Or did you have to make sacrifices along the way? Do you have any thoughts about that?
Rowley: That’s a very important question, especially for young people. I have two things to say on that. Firstly, as should have come out of my story, what has happened to me is totally unexpected. This is not something I strove for, was ever a goal, was ever anything I even conceived of almost anytime in my life. Not until the last fifteen years or so, when it was clear that what I had done was important; then my view of it changed. But this was never anything that I really sought.
What I think is important is that young people take a very long view of their life. Which implies that you’re going to have good health and I’m fortunate that that’s the case with me. Don’t be too impatient for things to all happen quickly. Or to think that by the time you’re thirty-five and you haven’t done very much, that you’re over the hill.
Because, again, translocations were discovered in 1972, and I was born 1925. So I was forty-seven years old before I did anything that people would really look at twice. So patience is certainly an important aspect of this. Then, I have to say that I was in an environment where people have been very supportive, very collegial, very patient, because sometimes I wasn’t as productive as I would have liked to be.
Collins: So basically, I think you’re suggesting that, yes there were a lot of pushes and pulls on your time, but you were patient enough to sort of let them find their appropriate place in your life. The role of serendipity comes across very clearly.
Rowley: Right and good luck. I have led, by and large, an extraordinarily lucky life. You just go from one thing to another. From retarded children, to chromosomes, to being in a hematology group, to banding. None of which you can predict ahead of time.
Collins: Yes. But of course others may have had that same luck and didn’t necessarily take the same advantage of it that you did.
Collins: You recognized an opportunity when it came along. And you stuck to it.
Collins: It’s clear. As you talked about those ten years, where you’re working away in this little lab in Chicago, pretty much by yourself, you didn’t give up. Did you ever feel discouraged? Did you ever sort of think, “Maybe I’m not really cut out to do research. Maybe I ought to just go back and be a clinical doc and give up all of this stuff?”
Rowley: No, I didn’t. But you see I think it goes back to what I said. I looked on medicine and research as a hobby. At the time that I started at the university, or a year after, I had four children. I had to be taking care of them. I only worked three days a week. So, I had a very rich, full life with my children and my husband.
The lab was a hobby. The fact that it was going slowly, well you know that didn’t bother me in the least. I never expected it to go anywhere anyhow. I shouldn’t be saying these things.
Collins: No, it’s wonderful you’re saying these things.
Rowley: Not on a web site.
Collins: Because it will be very reassuring to people who imagine that the only way you actually succeed in the competitive world of research, is becoming so single minded that you screen out every other aspect of your life. That would be a terrible message for people to receive, and you’re countering it very effectively.
Collins: Well Janet this has been a great pleasure for me to have the chance to lead you through this description. You’ve told me a bunch of things that I didn’t know before, about your past life and all the things you’ve done.
Again my heartiest congratulations to you for this accomplishment. You deserve it. We all celebrate it. We’re all smiling a lot after having heard this news.
Rowley: Well we can celebrate it at New York.
Collins: We will indeed.
Key Publications of Janet Rowley
Rowley, J.D. (1973) A new consistent chromosomal abnormality in chronic myelogenous leukemia. Nature 243: 290-293.
Rowley, J.D. (1975) Nonrandom chromosomal abnormalities in hematologic disorders of man. Proc. Natl acad Sci USA 72: 152-156.
Rowley, J.D., Golomb, H.M., and Vardiman, J.W. (1977) Nonrandom chromosomal abnormalities in acute nonlymphocytic leukemia in patients treated for Hodgkin’s disease and non-Hodgkin lymphomas. Blood 50: 759-770.
Thirman, M.J., Gill, H.J., Burnett, R.C., Mbankollo, D., McCabe, N.R., Kobayashi, H., Ziemin-van der Poel, S., Kaneko, Y., Morgan, R., Sandberg, A.A., Chaganti, R.S.K., Larson, R.A., LeBeau, M.M., Diaz, M.O., Rowley, J.D. (1993) Rearrangement of the MLL gene in acute lymphoblastic and acute myeloid leukemias with 11q23 chromosomal translocations. New Engl J. Med. 329: 909-914.
Rowley, J.D., Reshmi, S., Sobulo, O., Musvee, T., Anastasi, J., Raimondi, S., Schneider, N.R., Barredo, J.C., Cantu, E.S. Schlegelberger, B., Behm, F., Doggett, N.A., Borrow, J., Zeleznik-Le, N. (1997) All patients with the t(11;16)(q23;p13.3) that involves MLL and CBP have treatment-related hematologic disorders. Blood 90: 535-541.