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Landmark Paper in Hematology
recently discovered v-ABL gene.3 A further decade leap into the 1990s and it was demonstrated that BCR-ABL did indeed cause leukemia in a murine model.4 The founda- tion of “precision medicine” had been laid.
CML is perhaps the best example of the old “bench to bedside” adage and is an excellent model of the power of precision medicine since BCR-ABL is a target of treat- ment, and a biomarker of response. Soon after the inven- tion of the polymerase chain reaction, BCR-ABL mRNA was used to track disease response and predict relapse following allogeneic transplantation. Tyrosine kinase
References
inhibitors were found to inhibit BCR-ABL in vitro and were soon championed into the clinic. The combination of having a remarkably effective drug and a remarkably robust way of monitoring response completely changed the natural history of CML from a disease associated with a median lifespan of <7 years to one where patients now enjoy essentially a normal lifespan. It is difficult to under- estimate the accomplishments of these scientists and patients over a relatively short period of time.
In 1776 a revolution officially began in Philadelphia. In 1960, another one started.
1. Nowell PC, Hungerford DA. A minute chromosome in human chronic granulocytic leukemia. Science. 1960;142:1497.
2. Rowley JD. A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescene and Giemsa
staining. Nature. 1973;243(5405):290-293.
3.De Klein A, van Kessel AG, Grosveld G, et al. A cellular oncogene is translocated to the Philadelphia chromosome in chronic myelocytic
leukaemia. Nature. 1982;300(5894):765-767.
4. Daley GQ, Van Etten RA, Baltimore D. Induction of chronic myelogenous leukemia in mice by the P210 bcr/abl gene of the Philadelphia chro-
mosome. Science. 1990;247(4944):834-830.
5. Nowell PC, Hungerford DA. Chromosome studies on normal and leukemic human leukocytes. J Natl Cancer Inst. 1960;25(1):85-109.
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