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Acute myeloid leukemia
- 1.
- 2. Definition • It’s amalignant clonal disorders originating from hematopoietic stem cells characterized by the proliferation of poorly differentiated blast ( immature )cells in the bone marrow & rapidly progressive to fatal course if untreated • Survival < 6 months without treatment • Also k/w acute myelogenous leukemia, acute nonlymphocytic leukemia
- 3. Classification 1. FAB Classification(1976)– Based on Morphological & Cytochemical features 2. WHO Classification (2008)
- 4. FAB Classification • Granulocytic: •AML minimally differentiated - M0 • AML with out maturation - M1 • AML with maturation - M2 • Promyelocytic Leukemia - M3 • Monocytic: • Acute myelomonocytic - M4 • Acute Monocytic - M5 • Erythrocytic: • Acute erythroleukaemia - M6 • Megakaryocytic: • Acute megakaryocytic leukemia - M7
- 6. Predisposing factors Hereditary factors •Down’s syndrome • Fanconi’s anemia • Bloom’s syndrome • Ataxia telangiectasia • Klienfelter's syndrome • Diamond blackfan syndrome • Wiskott Aldrich syndrome • MDS,MPD Acquired factors • Ionizing radiation • Chemical radiation • Viruses
- 7. Pathogenesis •Recurrent genetic aberrationsof transcription factors which required for normal myeloid differentiation •Most common chromosomal rearrangements t(8;21) & inv (16) which disrupts the RUNX1 & CBFB genes respectively •t(15;17) – RARA/PML fusion gene rearrangement
- 8. Clinical features 1. Mostcommon in adults 2. Median age is 65 3. Anemia – weakness, fatigue 4. Granulocytopenia – infections 5. Thrombocytopenia – bleeding tendencies 6. Bone pain 7. Hepatomegaly less common 8. Splenomegaly 9. Lymphadenopathy rare •Gum hypertrophy M4,M5 •DIC – M3
- 9. Morphology • 20% blastcells in the bone marrow • Myeloblast: • Delicate nuclear chromatin • Two to four nucleoli • Abundant cytoplasm than lymphoblast • Cytoplasm contain fine peroxidase positive azurophilic granules • Auer rods – distinctive needle like azurophilic granules • Monoblast: • Folded or lobulated nuclei • Lack Auer rods • Nonspecific esterase positive • Occasionally blasts are entirely absent ( Aleukemic leukemia)
- 15. Investigations • Peripheral smear: •Anemia – Normocytic Normochromic • TLC – Low or markedly raised • Platelets – Reduced & often large , bizarre • Bone marrow: • 20% or more blasts in all nucleated cells in the marrow • Hyper cellular • Immunophenotype: • Positive for CD 33, 34 • Cytochemistry: • Myeloperoxidase positive ( M1,M2,M3,M4) • Nonspecific esterase positive ( M4,M5)
- 16. •Cytogenetic analysis: •Structural rearrangements •Gainor loss of whole or part of a chromosome
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