Introduction

Chronic myeloid leukemia (CML), historically also known as chronic myelogenous leukemia, chronic myelocytic leukemia, and chronic granulocytic leukemia, is a form of chronic myeloproliferative disease (CMPD) with a well-defined genetic defect known as the Philadelphia (Ph) chromosome.12 The Ph chromosome is associated with a BCR-ABL fusion gene expressed as an oncoprotein, p210BCR-ABL, which is generally considered as the initiating event for the chronic phase of CML. All CMPDs are clonal hematopoietic stem cell disorders characterized by proliferation in the bone marrow of one or more of the myeloid cell lineages that

Table 16.1 WHO classification of CMPD Chronic myeloid leukemia (also referred to as chronic myelogenous leukemia) Chronic neutrophilic leukemia

Chronic eosinophilic leukemia (and the hypereosinophilic syndrome)

Polycythemia vera

Chronic idiopathic myelofibrosis (with extramedullary hemopoiesis)

Essential thrombocythemia

Chronic myeloproliferative disease, unclassifiable gradually displaces normal haematopoiesis (Table 16.1). The remaining forms of CMPD do not have a specific genetic defect and the diagnosis, for the most part, relies upon clinical and hematologic features. The recent observations supporting the notion of JAK2 as a candidate gene involved in the molecular pathogenesis of some of the CMPD, specifically polycythemia vera, essential thrombocythemia and primary myelofibrosis, should herald an enhanced understanding of these disorders and might lead to a new classification of these disorders and, perhaps, novel treatments.3-5 In this chapter, we review the epidemiology, risk factors, and classification of CML.

CML originates in an abnormal hematopoietic stem cell, which acquires a Ph chromosome, and the BCR-ABL fusion gene, which is considered to be the principal pathogenetic event67 (Figure 16.1). The Ph chromosome and the BCR-ABL gene are found in all myeloid lineage cells and some, but not all, B and T lymphocytes. Clinically, CML is a biphasic or triphasic disease that is usually diagnosed in the initial "chronic" phase and then spontaneously evolves after a median time of 4-5 years into an "advanced" phase, which resembles an acute leukemia. The transformation into an advanced phase (called blast crisis) can occur abruptly or via a period of acceleration (called accelerated phase).

Figure 16.1 A peripheral blood film of a patient with classical CML
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