ABSTRACT
The story of what we now know as chronic myeloid leukemia (CML) began in the early 19th century as a result of astute clinical observations. Thereafter, with the dawn of the era of medical microscopy and the use of anilinebased dyes to stain human tissues, leukemias were recognized as a distinct nosological entity. Many of the initial efforts focused on therapy and led to the introduction of arsenicals in the later part of the 19th century for symptomatic relief. This was largely supplanted by the introduction of ionizing radiation at the beginning of the 20th century and later by the alkylating agent, busulfan, though many hematologists were suspicious that this agent might, in some cases, expedite transformation of the initial chronic phase to the more advanced phases of CML. Major progress in both the therapy and, indeed, the understanding of the disease did not occur until 1960 when advances in the technology of cytogenetics led to the discovery of a consistent chromosomal abnormality in bone marrow cells of patients with CML. This was later termed the ‘Philadelphia ’ or Ph 1 chromosome to acknowledge the city where the discovery took place. The era of molecular biology unfolded in the early 1980s, and led to the molecular unraveling of the ‘pathogenetic ’ or apparent ‘initiating ’ event for the chronic phase of CML. This, in turn, paved the way to the successful introduction of the original ABL kinase inhibitor, imatinib mesylate, as initial treatment for the majority of, if not all, newly diagnosed patients in chronic phase. In this chapter we address the principal historical events leading to the current treatment
algorithms for the various phases of CML. The chronology of events is summarized in Table 1.1 and Figure 1.1.
