ABSTRACT
INTRODUCTION 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 aniline-based 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. Major progress in both the therapy and, indeed, the understanding of the disease did not occur until 1960 when advancements 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 (Ph1) 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 (CP) of CML. This, in turn, paved the way to the successful introduction of the original ABL kinase inhibitor, imatinib, as the preferred initial treatment of newly diagnosed patients in CP. The chronology of evolution of therapy is summarized in Figure 2.1.
