Chronic Myeloid Leukemia (CML): Pathogenesis and Clinical Presentation
Translocation of a Chr 9 segment onto Chr 22, creating a Philadelphia chromosome (Chr 22) containing the BCR-ABL1 fusion gene
Mutations from ionizing radiation
Other genetic abnormalities
Authors: Yan Yu Katie Lin Reviewers: Jennifer Au Crystal Liu Danielle Chang Lynn Savoie* *Indicates faculty member at time of initial publication
These genetic abnormalities accumulate in the earliest cell of the blood cell differentiation sequence: the pluripotent hematopoietic stem cell
Hematopoietic stem cell division in the bone marrow becomes unregulated
1. Chronic Stage (85% of clinical presentation): Hematopoietic stem cell division/differentiation in the bone marrow results in ↑ production of multiple blood cell lines (detectable on CBC, but patients are usually asymptomatic at this stage)
Acquired ↑ genetic abnormalities
2. Accelerated Stage
More and more immature precursor cells (”blasts”) divide and accumulate in bone marrow (where 10-19% of blood cells are “blasts”.) Blasts start to spill over into the peripheral blood
Acquired ↑ genetic abnormalities
3. Blast crisis (transformation into AML/ALL)
Neoplastic blast cells have filled up the bone marrow (where >20% of blood cells are blasts). More blasts spill out into the peripheral blood.
Multifactorial causes, most Weight loss, malaise, fever/
with unclear mechanisms
Neoplastic division of platelet precursor cells
Neoplastic division of WBC precursor cells, especially neutrophil precursors
Dividing “blasts” limit the space and resources available for RBC synthesis
chills, night sweats Thrombocytosis
· Neutrophilia, basophilia, & eosinophilia
· “Left shift”: ↑ neutrophil & band production
· Disorderly WBC differential: i.e. “myelocyte bulge”
Trapping of WBC’s in the spleen enlarges the spleen
· Left upper quadrant pain · Early satiety (large spleen compresses the stomach)
· Associated hepatomegaly (if spleen is overfilled & WBCs spill over into liver)
↓ oxygenation of blood means blood is less red & body tries to compensate
Pallor Dyspnea Tachycardia
High turnover of these cancerous cells → excess cell lysis
Release of intracellular contents (uric acid, K+, LDH) into plasma
· Hyperkalemia · High (LDH)
Acute Kidney Injury
Expanding marrow pushing on bone
Bone marrow expands into sternum
Bone pain
Sternal tenderness
Sign/Symptom/Lab Finding
Re-Published June 15, 2019 on