1. Pathophysiology
1.1. BCR-ABL1 fusion gene results from the Philadelphia chromosome translocation (t[9;22]), leading to constitutive tyrosine kinase activity.
1.2. Uncontrolled myeloid proliferation due to signaling abnormalities.
2. Risk Factors
2.1. Radiation exposure
2.2. Genetic predisposition (Philadelphia chromosome)
2.3. Age (most common in adults)
2.4. Gender: Slight male predominance
3. Clinical Presentation
3.1. Chronic phase
3.1.1. Fatigue
3.1.2. Weight loss
3.1.3. Night sweats
3.1.4. Splenomegaly
3.2. Accelerated phase:
3.2.1. Progressive anemia
3.2.2. Progressive splenomegaly
3.2.3. weight loss
3.3. Blast crisis:
3.3.1. Fever and pains
3.3.1.1. Bone pain
3.3.1.2. Frequent headaches
3.3.1.3. Arthralgias
3.3.1.4. Abdominal splenic
3.3.2. Symptoms due to platelet dysfunction, generally related to thrombocytosis
3.3.2.1. Easy bruising
3.3.2.2. Spontaneous bleeding
3.3.3. Dyspnea, incoordination, drowsiness, and confusion or cognitive dysfunction
3.3.4. Hyperviscosity symptoms
3.3.4.1. tinnitus
3.3.4.2. priapism
3.3.4.3. visual changes
4. Definiton
4.1. A clonal hematopoietic stem cell disorder characterized by uncontrolled proliferation of myeloid cells.
5. Classified into
5.1. Chronic Phase: Mild symptoms, manageable with treatment, typically the longest phase.
5.2. Accelerated Phase: Increased symptoms, worsening blood counts, more aggressive treatment needed.
5.3. Blast Crisis: Severe symptoms, transformation into acute leukemia, requires immediate intervention.
6. Diagnosed by
6.1. Blood Test - Checking complete blood count (CBC) for elevated white blood cells.
6.2. Conducting Bone Marrow Biopsy: Extracting marrow sample to look for abnormal cells.
6.3. Detecting Philadelphia Chromosome: Using fluorescence in situ hybridization (FISH) or PCR to identify BCR-ABL gene fusion.
6.4. Testing for BCR-ABL1: Molecular testing for BCR-ABL1 gene mutation confirming CML diagnosis.
7. Treatment
7.1. Tyrosine kinase inhibitors (TKIs)
7.1.1. Imatinib (first-line)
7.1.2. Dasatinib, Nilotinib (2nd-generation)
7.2. Stem cell transplantation
7.2.1. In cases of TKI resistance or blast crisis
7.3. Chemotherapy
7.3.1. For blast crisis
7.4. Managment
7.4.1. Managment of symptoms such as fatigue, splenomegaly, weight loss, and night sweats.
7.4.2. Mitigating TKI side effects like fluid retention, nausea, and muscle cramps.