Chronic Myelogenous Leukemia (CML) is a myeloproliferative disease characterized by proliferation of myeloid cells capable of differentiation. CML is caused by a reciprocal translocation t(9;22), in which a piece of chromosome 9 containing the ABL1 oncogene is translocated to chromosome 22 and fused to the BCR gene. The resulting Philadelphia chromosome harbors the BCR-ABL fusion gene which produces a tyrosine kinase implicated in the pathogenesis of CML.
The clinical course of CML is divided into three phases:
Chronic phase: Blasts < 10%, may last months to years. Most patients present in the chronic phase and are typically asymptomatic.
Accelerated phase: Blasts 10-19%, worsening anemia, treatment failure, progressive splenomegaly, and increasing white cell count.
Blast phase: Blasts > 20%, accumulation of blasts in extramedullary sites.
Treatment options include allogeneic hematopoietic stem cell transplantation (HSCT), hydroxyurea, and BCR-ABL tyrosine kinase inhibitors (e.g., imatinib, dasatinib, nilotinib).