Overview
Definition
A clonal myeloproliferative disorder characterized by the neoplastic proliferation of the granulocytic lineage, defined by the presence of the Philadelphia chromosome.
Epidemiology
Accounts for 15% of adult leukemias. Median age at presentation is ~50-60 years.
Etiology & Risk Factors
- Reciprocal translocation t(9;22) forming the BCR-ABL1 fusion gene (Philadelphia chromosome), encoding a constitutively active tyrosine kinase
Clinical Symptoms
- Insidious onset of fatigue, weight loss, night sweats
- Splenomegaly (causing early satiety and abdominal fullness)
- Easy bruising or bleeding
- Often asymptomatic (detected on routine CBC)
Clinical Approach
Diagnosis
- Marked leukocytosis with entire spectrum of myeloid cells (neutrophils, metamyelocytes, myelocytes, blasts)
- Basophilia and eosinophilia
- FISH or RT-PCR showing the BCR-ABL1 fusion gene/transcript
- Bone marrow biopsy
Management
- Tyrosine Kinase Inhibitors (TKIs: Imatinib, Dasatinib, Nilotinib) - highly effective first-line therapy
- Allogeneic stem cell transplant for TKI-resistant cases or blast crisis
Complications
- Progression from chronic phase to accelerated phase and blast crisis (resembling AML or ALL, fatal if untreated)
- Hyperviscosity syndrome (rare)