Pathophysiology of AML
AML is:
group of disorders (at least nine different variants) in which a hematopoietic stem cell becomes neoplastic or alternately an individual lineage of stem cells (e.g., erythrocytes, monocytes, granulocytes, or megakaryocytes) becomes neoplastic
Signs and Symptoms
1) usually presents with signs of anemia – pallor, fatigue, weakness 2) splenomegaly 3) hepatomegaly 4) hemorrhage in GI tract and CNS if platelets are < 20,000/dL 5) dyspnea owing to infiltration of lung by leukocytes 6) secondary infections 7) gingival hyperplasia
Characteristic Test Findings
Bone marrow – 1) by definition, > 30% of nucleated cells are blasts Laboratory – 2) anemia 3) thrombocytopenia 4) neutrophilia (but total leukocyte count may be increased or decreased)
Histology/Gross Pathology
1) accumulation of blasts infiltrate and replace normal marrow 2) marrow fibrosis 3) Pelger-Huet cells with bilobed leukocytes and dense chromatin 4) Auer rods
Pelger-Huet cell is center or photo with dark bilobed nucleus (photo courtesy Wikimedia Commons)
Associated Conditions
1) 20-40% of myelodysplastic syndromes convert to acute myelogenous leukemia 2) increased incidence with – Down’s syndrome, Fanconi’s anemia, Bloom’s syndrome, paroxysmal nocturnal hemoglobinuria, benzene exposure, alkylating agents, radiation (if > 100 rads (cGy)
Biochemistry
1) neoplastic event is failure of affected cell to mature 2) arrested development with accumulation of these blasts occurring in the bone marrow
Inheritance/Epidemiology
1) makes up 20% of all leukemias in Western nations 2) 85% of all adult leukemias 3) 20% of all childhood leukemias 4) slightly more prevalent in men 5) occurs as a “superimposed” terminal event in myeloproliferative disorders 6) occured as “blast crisis” in 80% of cases of chronic myelogenous leukemia before the advent of Gleevec 7) specific variations correspond to specific genetic defects – translocations between chromosomes 15 and 17 and 8 and 21, deletions in chromosomes 5 and 7 and trisomy 8 8) poor prognostic indicators are > 60 years of age at diagnosis, deletions on chromosomes 5 and 7, prior chemotherapy or radiation, severe leukocytosis (> 100,000 cells/dL)
Tips for USMLE
the key pathologic problem is accumulation in the bone marrow of immature myelogenous cells that are in arrested development and replace the normally developing cells
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