This document provides information about acute myeloid leukemia (AML), including its definition, classification, predisposing factors, pathogenesis, clinical features, morphology, investigations, and prognosis. AML is a malignant clonal disorder originating from hematopoietic stem cells characterized by proliferation of immature blast cells in the bone marrow with a rapidly fatal course without treatment. It is classified based on morphological and cytogenetic features, with common genetic abnormalities involving transcription factors required for normal myeloid differentiation. Prognosis depends on specific cytogenetic abnormalities, with translocations like t(8;21) and inv(16) conferring a better prognosis.

1. ACUTE MYELOID
LEUKEMIA
Dr.T.Arivazhagan
Post graduate
Dept. of Pathology

2. Definition
• It’s a malignant 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 aberrations of 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. Most common 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% blast cells 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
•Gain or loss of whole or part of a chromosome

17. Prognosis
Good
•t(8;21)
•Inv(16)
•t(15;17)
Bad
•Abnormalities of
11q23
• -5,5q-,-7,7q-
,+8,+9,+11,11q-,12p-