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March 2000, Volume 14, Number 3, Pages 511-512
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Monograph from the Acute Leukemia Forum 1999 on Advances and Controversies in the Therapy of Acute Myelogenous Leukemia
Introduction to Janet D Rowley
E Beutler

Department of Molecular and Experimental Medicine, The Scripps Research Institute, (MEM-215), 10550 North Torrey Pines Road, La Jolla, CA 92037-1027, USA

Correspondence to: E Beutler

It gives me great pleasure to introduce Janet Rowley, whom I have known and admired for half a century. As a scientist, she does not require an introduction for her achievements are renowned. I would like to provide you with some of the background behind her major contributions to science.

Janet was born in New York, but her family moved to Chicago before she was 2 years of age and she has been a Chicagoan most of her life. She attended what was then known as a 4-year college, a program instituted at the University of Chicago by Robert Maynard Hutchins, who was the chancellor at that time. This program was predicated on the idea that the conventional last 2 years of high school were essentially wasted time. These years, plus the first 2 years of college, could provide a student with a broad, general education. There was ample time, Hutchins felt, for specialization afterwards. Janet's and my university educations ran a parallel course. I entered the program a few years after she did and if it had as profound an influence on her as it did on me, it would be fair to state that her spectacular professional success may have been related to this solid foundation of knowledge.

In 1948, 2 years before I graduated from the same school, Janet received her MD from the University of Chicago. After an internship in the Public Health Service and a short stint in infant welfare in prenatal clinics, she began studying neurology. Her work with retarded children and Lejeune's1 1959 report of chromosome 21 in Down's syndrome sparked her interest in cytogenetics. She received a Public Health Service special training fellowship to study cytogenetics in Oxford and, based on this experience, she was appointed as a research associate at the University of Chicago in 1962. It was here that she carried out studies of the replication of normal and abnormal chromosomes.

Janet married Don Rowley in the late 1940s and they recently celebrated their golden wedding anniversary. Her family has always been of great importance to her and she now enjoys four grandchildren. From 1962 to 1975, she was raising her four children and thus worked on her research only 3 days a week. Nonetheless, she became an associate professor in 1971 and a full professor in 1978.

The 1960s and early 1970s were difficult and often unrewarding days for those studying the cytogenetics of human disease. Lejeune's observations and the subsequent description of the Philadelphia chromosome by Nowell and Hungerford in 1961,2 were beacons that made this a tantalizing area for study. Indeed, there was enough interest in cytogenetics that we included a chapter on this topic in the 1972 first edition of Williams Hematology. In it, Peter Nowell wrote, 'In acute leukemia with chromosome abnormalities, the variations are considerable from minor rearrangements in diploid chromosome sets to marked changes in both chromosome numbers and morphology. Perhaps the most extensive alterations have been observed in some of the acute lymphoblastic leukemias of childhood. In general, when present the abnormalities have been clonal in nature. Each case has been characterized by a single stem cell line or small number of stem cell lines showing related chromosomal changes.' But he went on to write, 'The alterations have differed from case to case.

Although there have been some indications that certain chromosome groups are more prominently involved than others, particularly groups C and D, it has been unusual to find more than two or three patients in any series of acute leukemias with the same chromosomal change. Nor has it been possible to relate any particular alteration to a characteristic clinical or hematologic picture.1,3 In view of the lack of uniformity in findings, perhaps hematologists could be pardoned for regarding the changes that did occur as being some kind of secondary phenomenon that was of no real importance. Perhaps the editors of Williams Hematology should also be pardoned for eliminating the chapter on cytogenetics in Edition 2, 1977, and Edition 3, 1983, including some of the material in chapters dealing with specific forms of leukemia and with genetic principles. However, in Edition 4, published in 1989, we again included a chapter on cytogenetics and I am proud to say that it was written by Janet and her colleague, Michelle Le Beau.

Janet's faith that there was knowledge to be gained by studying the chromosomes of patients with leukemia and other neoplastic disorders turned out to be spectacularly correct. Because of her work and leadership in this area, we have come to understand better the pathogenesis, diagnosis, and treatment of tumors. It was her recognition that the Philadelphia chromosome was not a deletion from chromosome 21 or chromosome 22, as has had been thought, but a translocation of a fragment from chromosome 22. I well remember her presentation of this landmark paper at the Young Turks meeting in about 1973. When Janet presented the paper, there was not a single question. I started to stand up to say what a great piece of work I thought it was, but then refrained from commenting, feeling that perhaps it would be presumptuous and maybe even appear patronizing for me to make such a comment, especially about a field in which I was not working actively. It is interesting to note that her 1973 paper in Nature4 was a single-author paper, something that we very rarely see these days.

This was a turning point in the application of chromosome analysis to malignant processes, and to Janet's career as well. Her investigations of patterns of chromosome rearrangements in the leukemias has led to recognition of a number of gene alterations that are of etiologic importance and that have pointed to the basic biochemical abnormality. Moreover, they have been extremely important in allowing one to stratify patients by risk.

Janet has received recognition for her seminal studies from all over the world. She was awarded the Dameshek Prize at the American Society of Hematology in 1982; was elected to the National Academy of Sciences in 1983; presented the Stratton Lecture at the International Society of Hematology in 1986; the Karnofsky Lecture at the American Society of Clinical Oncology in 1987; won the Mott prize from the General Motor Cancer Research Foundation in 1989; received the Allen Award from the American Society of Human Genetics 1991; served as President of the American Society of Human Genetics in 1993; was given the Gairdner Award in 1996; the Albert Lasker Clinical Research Award in 1998; and the National Medal of Science in 1998. In addition, she has been recognized by receiving five honorary degrees. I know you will all join me in welcoming Janet Rowley to this meeting and be interested in hearing her keynote address on molecular genetics in acute leukemia.

References

1 Lejeune J, Gauthier M, Turpin R. Etude des chromosomes somatiques de neuf enfants mongoliens. CR Acad Sci 1959; 248: 1721,

2 Nowell PC, Hungerford DA. Chromosome studies in human leukemia. II. Chronic granulocytic leukemia. J Natl Cancer Inst 1961; 27: 1013-1021,

3 Williams WJ, Beutler E, Erslev AJ, Rundles RW (eds). Hematology, 1st edn. McGraw-Hill: New York, NY, 1972,

4 Rowley JD. A new consistent chromosomal abnormality in chronic myelogenous leukemia identified by quinacrine fluorescence and Giemsa staining. Nature 1973; 243: 290-293, MEDLINE

Received 25 October 1999; accepted 2 November 1999
March 2000, Volume 14, Number 3, Pages 511-512
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