Overview
Clinical Meaning
Chronic myeloid leukemia (CML) is defined by the Philadelphia chromosome t(9;22), which creates the BCR ABL fusion oncogene encoding a constitutively active tyrosine kinase.
PMHNP
PMHNP
Chronic myeloid leukemia (CML) is defined by the Philadelphia chromosome t(9;22), which creates the BCR-ABL fusion oncogene encoding a constitutively active tyrosine kinase. This drives unregulated myeloid proliferation and resistance to apoptosis. CML progresses through three phases: chronic (>90% of patients at diagnosis; leukocytosis with left shift, basophilia, splenomegaly), accelerated (10-19% blasts, increasing basophilia, cytogenetic evolution), and blast crisis (≥20% blasts, behaves like acute leukemia with poor prognosis). Tyrosine kinase inhibitors (TKIs) revolutionized treatment: imatinib was the first targeted therapy, binding the ATP-binding site of BCR-ABL and reducing its kinase activity. Second-generation TKIs (dasatinib, nilotinib, bosutinib) have greater potency and overcome many imatinib-resistant mutations, except the T315I gatekeeper mutation (treated with ponatinib).
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