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chronic-myeloid-leukemia

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 Leukocytosis: · 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 Splenomegaly: · Left upper quadrant pain · Early satiety (large spleen compresses the stomach) · Associated hepatomegaly (if spleen is overfilled & WBCs spill over into liver) Anemia ↓ 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) Hyperuricemia Gout Acute Kidney Injury Expanding marrow pushing on bone Bone marrow expands into sternum Bone pain Sternal tenderness Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published June 15, 2019 on www.thecalgaryguide.com