AML

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-