Chronic myelocytic leukemia—Part I: History, clinical presentation, and molecular biology

Department of Clinical Laboratory Science, Doisy School of Allied Health Professions, Saint Louis University Health Sciences Center, 3437 Caroline St, St Louis, MO 63104-1111, USA.
Clinical laboratory science: journal of the American Society for Medical Technology 02/2005; 18(1):38-48.
Source: PubMed


DATA SYNTHESIS: Chronic myelocytic leukemia (CML) was initially described in 1845 and is considered one of the first leukemias to be discovered. Diagnosis of CML was dramatically improved with the discovery of the Philadelphia chromosome by Nowell and Hungerford in 1960. However, the rudiments of our understanding of the molecular cause of CML began in 1973 when Janet Rowley discovered that the Philadelphia chromosome is a reciprocal translocation between chromosomes 9 and 22. The leukemogenic mechanisms of CML were hypothesized 20 years later when it was discovered that the t(9;22) translocation produced a fusion gene involving the BCR gene from chromosome 22 and the ABL protooncogene from chromosome 9 [corrected] Multiple breakpoints in BCR produce fusion genes that are translated into chimeric protein products of different lengths that are associated with different leukemic subtypes. CONCLUSION: Although CML has a rich history of interest to hematologists, it also represents a leukemogenic paradigm to the molecular biologist. Nearly all malignancies result from a series of mutagenic events, which culminate in full malignant transformation. However, it appears that CML results from a single mutagenic event involving the t(9;22) translocation leading to the development of the BCR/ABL fusion gene and the corresponding fusion protein. The successful transcription and translation of the BCR/ABL fusion protein led researchers to carefully study its involvement in leukemogenesis. The BCR/ABL fusion protein exhibits increased and constitutive tyrosine kinase activity that differs depending on which BCR breakpoint is expressed, resulting in varying clinical presentations.

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