Chronic Myeloid Leukemia — A Brief History

  • John M. Goldman
  • George Q. Daley
Part of the Hematologic Malignancies book series (HEMATOLOGIC)


Leukemia was first recognized as a distinct nosological entity in the early part of the 19th century and some of the early descriptions are highly suggestive of chronic myeloid leukemia (CML). The first important contribution to understanding the biological basis of CML was the discovery of the Philadelphia (Ph) chromosome in 1960. Almost equally important was the demonstration in 1973 that it resulted from a reciprocal translocation involving chromosomes 9 and 22. In the 1980s a “breakpoint cluster region” of the Ph chromosome was defined and this led fairly rapidly to the recognition that patients with CML had in their leukemia cells an acquired BCR-ABL fusion gene that was expressed as a protein with greatly enhanced tyrosine kinase activity. In 1990 BCR-ABL was shown to induce CML in murine models, thereby proving its central role in disease causation. Treatment for CML in the 19th century was rudimentary. The only agent known to be effective was arsenic. Radiotherapy and subsequently alkylating agents and hydroxyurea became the mainstay of therapy from the beginning of the 20th century until the advent of interferon-alfa in the early 1980s. During the 1980s it also became clear that allogeneic stem cell transplantation, though not without risk of mortality, could result in long-term disease-free survival and probably cure for selected patients. The introduction to the clinic of the original tyrosine kinase inhibitor (STI571, now imatinib) in 1998 has revolutionized approaches to the management of the newly diagnosed patient with CML in chronic phase.


Chronic Myeloid Leukemia Chronic Phase Chronic Myelogenous Leukemia Chronic Myeloid Leukemia Patient Breakpoint Cluster Region 
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Copyright information

© Springer Berlin Heidelberg 2007

Authors and Affiliations

  • John M. Goldman
    • 1
  • George Q. Daley
    • 2
  1. 1.Hematology Branch, National Heart, Lung and Blood InstituteNational Institutes of HealthBethesdaUSA
  2. 2.Division of Hematology/OncologyChildren’s HospitalBostonUSA

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