CML is a hematopoietic proliferative disorder associated with a specific gene defect and a very characteristic blood picture.5 Synonyms for this disorder include chronic granulocytic leukemia and chronic myelocytic leukemia. There is a marked neutrophil leukocytosis with some circulation of immature neutrophils and an increase in basophils. The gene defect is the translocation of genetic material between chromosome 9 and chromosome 22 (t9:22), which is positive in 90% to 95% of the cases.6,7 This gene mutation is called the Philadelphia chromosome, or Ph1. This translocation leads to a formation of a hybrid gene called BCR-ABL. This fusion gene mutation affects maturation and differentiation of the hematopoietic cells.
This disorder is usually diagnosed in the chronic phase of the disorder. The peripheral blood picture shows an extremely high WBC with the whole spectrum of neutrophilic cell development seen. As the disease evolves, the chronic phase will deteriorate to an aggressive or accelerated phase and terminate in an acute phase or blast crisis. CML is one of the most common forms of chronic leukemia.1 See Table 12.3 for a summary of key facts for CML.
CML is a clonal proliferative disorder. The hallmark of the initial phase is the excess of mature neutrophils in the peripheral blood. The expansion of the myeloid cell results in an alteration of self-renewal and differentiation. There now is an increase in cells. The formation of the Philadelphia chromosome plays a significant role in the understanding of the pathogenesis of CML.
The main portion of the long arm of chromosome 22 is deleted and translocated to the distal end of the long arm of chromosome 9. This results in an elongated chromosome 9 or 9q+. A small part of chromosome 9 is then reciprocally translocated to the broken end of 22 or 22 — . This now forms the BCR-ABL hybrid gene, which codes for a 210-kDa protein, or p210, which has increased tyrosine kinase activity.5,8 Tyrosine kinase activity provides an important mediator to regulate metabolic pathways causing abnormal cell cycling. The activation of tyrosine kinase activity may suppress apoptosis (natural cell death) in hematopoi-etic cells and provide the mechanism for excess cell production.6,9
Most patients are diagnosed in the chronic phase. Many patients are asymptomatic and are diagnosed when an elevated white count is found on a routine complete blood count (CBC). Common findings include fatigue,
Table 12.3 O Key Facts of CML
• Clonal stem cell disorder
• Marked leukocytosis with all stages of granulocyte maturation
• Thrombocytosis is common in chronic phase
• Three phases: chronic, accelerated, blast
• Philadelphia chromosome
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