Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells. The main pathological changes in AML involve abnormal proliferation, blocked differentiation, and abolished apoptosis of hematopoietic stem and progenitor cells. Benzene exposure can cause AML and other hematological malignancies. AML is classified based on the type of cells affected and how quickly the disease progresses. The disease involves accumulation of genetic mutations in oncogenes and tumor suppressor genes, leading to increased proliferation, reduced apoptosis, and a block in cellular differentiation. Clinical manifestations include marrow failure, tissue infiltration, and leukostasis. Prognostic factors include age, white blood cell count, specific genetic mutations, and disease characteristics

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2. ACUTE LEUKEMIA'S
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The main pathological changes of AML involve the dysfunctions of hematopoietic
stem and progenitor cells including the abnormal proliferation, blocked
differentiation and abolished apoptosis. Benzene is one of the widely used
chemicals in petrol and an environmental leukemogenic element that can cause
AML and haematological malignancies.

3. Leukemia:
All leukemia's are stem cell/ and or precursor of HSC
disorders characterized by malignant neoplastic
proliferation and accumulation of immature and
nonfunctional haemopoietic cells in the blood and bone
marrow.
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4. DISEASE PROGRESSION
• Leukemia's are cancer found in the blood cells.
• Acute leukemia are usually aggressive disease.
• They are classified by how quickly they progress and
what type of cell they affect.
• Leukemia affects ability to produce normal blood cells.
• Bone marrow makes abnormally large number of
immature white blood cells called blasts.
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5. Hematopoietic
stem cell
Neutrophils
Eosinophils
Basophils
Monocytes
Platelets
Red cells
Myeloid
progenitor
Lymphoid
progenitor
B-lymphocytes
T-lymphocytes
Plasma
cells
naïve
ALL
AML
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CLL
PCD
CML
Mo
M1
M2
M3
M4
M5
M6
M7
M8

6. Leukemia
Acute
Chronic
ALL
AML
CML
CLL
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7. ACUTE LEUKEMIA
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8. PATHOGENESIS OF ACUTE LEUKAEMIA
Acute leukaemias are usually aggressive diseases in which
malignant transformation occurs in the haemopoietic stem cell or
early progenitors.
• Genetic damage is believed to involve several key biochemical
a. An increased rate of proliferation;
b. Reduced apoptosis
c. A block in cellular differentiation.
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9. ACUTE LEUKAEMOGENESIS
• Malignant transformation occurs as a result of the accumulation of
genetic mutations .
• Genes involved in the development of cancer are divided broadly into two
groups:
a. Oncogenes
An oncogene is a gene that has the potential to cause cancer. In tumor cells, these
genes are often mutated, or expressed at high levels. Most normal cells will
undergo a programmed form of rapid cell death (apoptosis) when critical functions are
altered and malfunctioning.
a. Tumour-suppressor genes
A tumor suppressor gene, or anti-oncogene, is a gene that regulates a cell during
cell division and replication. If the cell grows uncontrollably, it will result in cancer
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10. CLINICAL MANIFESTATIONS
• Symptoms due to:
• Marrow failure
• Tissue infiltration
• Leukostasis
• Other (DIC)
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11. MARROW FAILURE
• Neutropenia:
Infections, sepsis
• Anemia:
Fatigue, pallor
• Thrombocytopenia:
Bleeding
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12. INFILTRATION OF TISSUES/ORGANS
• Enlargement of liver, spleen, lymph nodes
• Gum hypertrophy
• Bone pain
• Other organs: CNS, skin, testis, any organ
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13. • Accumulation of blasts in
microcirculation with impaired
perfusion.
• Lungs: hypoxemia, pulmonary
infiltrates
• CNS: stroke
• Fever and sweats………… common
• Weight loss ……………less common
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14. ACUTE MYELOID LEUKAEMIA
• Acute myeloid leukaemia (AML) has an incidence of
• 2 – 3 per 100 000 per annum in children,
• rising to 15 per 100 000 in older adults
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15. MYELOID MATURATION
myeloblast promyelocyte myelocyte metamyelocyte band neutrophil
MATURATION Adapted and modified from U Va website
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16. CLASSIFICATION OF LEUKEMIA
FAB classification (Older)
• based upon morphology as determined by the degree of
differentiation along different cell lines and the extent of cell
maturation.
• 30% blast in blood and bone marrow.
WHO classification (Newer)
• Incorporates and interrelates morphology, cytogenetic,
molecular genetics, and immunologic markers.
• 20% blast in blood and bone marrow.
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18. LEUKOSTASIS
• Leukostasis is defined as clinical symptoms
and signs in the presence of an absolute
myeloblast count greater than 50,000/mm3
in AML,
• an absolute lymphoblast count of greater
than 100,000/mm3 in ALL or lymphocyte
count greater than 300,000/mm3 in CLL.
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PROGNOSTIC FACTORS IN AML
• Favorable
• younger age
(<50)
• WBC <30,000
• t(8;21) – seen in
>50% with AML
M2
• inv(16) – seen in
AML M4 eos
• t(15;17) – seen
in >80% AML
M3
• Unfavorable
• older age (>60)
• Poor performance status
• WBC >100,000
• Elevated LDH
• prior MDS or hematogic
malignancy
• CD34 positive phenotype,
MRD1 postive phenotype
• del (5), del (7)
• trisomy 8
• t(6;9), t(9;22)
• t(9;11) – seen in AML M5
• FLT3 gene mutation (seen in
30% of patients)

20. PERIPHERAL BLOOD AML
• Most patients with AML present with anemia normocytic normochromic.
• Thrombocytopenia
• Leukocytosis white blood cell count up to 200x109
• Large, sometimes hypogranular platelets can be seen, and functional defects can
contribute to hemorrhagic manifestations.
• Most patients are neutropenic, and morphologic abnormalities (hypogranulation,
nuclear hyperlobulation, Pelger-Huët anomaly) are often noted in the remaining
neutrophils.
• Blasts are predominant cells.
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21. BM CHANGES IN AML
BM aspirates show
 Hypercellularity
 Cells predominantly myeloblasts
 Immature granulocytes, erythroblasts, modest increase in plasma cells,
monocytes, megaloblastic erythroblasts,ring sideroblasts.
 Erythropoeitic cells scanty, megaloblasts, ring sideroblasts found
 Megakaryocytes reduced
 Myelofibrosis can be seen
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22. BLAST CLASSIFICATION
Type 1
Typical myeloblast with open chromatin and prominent
nucleoli, immature deep blue cytoplasm without granules.
Type 2
Similar to type one + presence of up to 20 discrete
azurophilic granules.
Type 3
Similar to type one + numerous azurophilic granules.
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23. AML-MO (M0: MINIMALLY DIFFERENTIATED)
• Distinguished by absence of visible granules in cytoplasm of blast.
• Negative –ve reactions with cytochemical stains.
• Positive +ve for myeloid lineage markers.
CD13 CD33.
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24. M0 AML
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25. AML-M1 (AML WITHOUT MATURATION)
• AML variant and is most common in adults and in infants less then 1
year.
• 50% cases show leucocytosis.
• Lack of cellular maturation.
• Predominant cell in peripheral blood is poorly differentiated
myeloblast.
• Vacuoles may be present.
• Platelet are generally decreased.
• A few blast may have scanty azurophilic granules or Auer rod is
present.
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26. PB film of a patient with M1 AML showing blasts, some of which
are heavily vacuolated
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27. AML-M2 (MYELOBLASTIC LEUKEMIA WITH MATURATION)
• Presence of more differentiated cells in the bone marrow with maturation.
• Condition is more common in adults.
• Leucocytosis in 50% of cases.
• Thrombocytopenia
• Myeloblast are predominant cell type in peripheral blood.
• Bone marrow is hypercellular.
• Azurophilic granules in variable amount.
• Auer rods a azurophilic granules are common.
Phi bodies:
Phi bodies are variant of auer rods but are smaller and not necessarily
in rod shaped.
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28. BM film of a patient with M2 AML showing unusually
heavy granulation of neutrophils and precursors
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29. AML-M3(HYPER GRANULAR PROMYELOCYTIC LEUKEMIA
• Typically seen in young adults.
• Sudden and severe progression.
• Cause acute DIC.
• DLC shows predominance of promyelocytes.
• Nucleus is very delicate sometime show
foldings.
• Most common clinical finding is bleeding.
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30. AUER RODS
• Auer rods are red staining, needle-like bodies seen in
the cytoplasm of myeloblasts, and/or progranulocytes
in certain leukemias. Auer rods are cytoplasmic
inclusions which result from an abnormal fusion of
the primary (azurophilic) granules.
•
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31. FAGGOT CELLS:
Faggot cells:
Cells with multiple auer rods sometime occuring in
bundles.
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32. AML-M4 (MYELOMONOCYTIC LEUKEMIA)
• Both myelocytic and monocytic cells are present in peripheral blood and
bone marrow.
• Infiltration of leukemic cells in extramedullary sites is more common.
• Serum and urine level of meuramidase are usually elevated because of
monocytic proliferation.
• Anemia
• Thrombocytopenia
• Cytochemical stains will demonstrate two cells population in bone marrow.
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33. AML-M4
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34. AML-M5 (MONOCYTIC LEUKEMIA)
• Usually seen in children and young adults.
• Degree of gum hypertrophy ,lymph node ,CNS and extra
medullary infiltrates seen.
• Occasional episods of DIC.
• Moderately elivated serum and urine muramidase.
• More then 80% of non erythroid cells seen in BM are
monocytic .
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35. AML-M5 ( M5A & M5B)
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36. AML-M5A
• Poorly differentiated.
• Monoblast account for 80% or more of all monocytic
cells.
• Remeining 20% are monocytes.
• The monoblast are larger.
• Azurophilic granules may be present.
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37. AML-M5B
• Well differentiated.
• More then 80% of monocytic cells in nonerythroid marrow.
• The remaining cells are promonocytic or monocytic.
• The percentage of blast is less then 30%.
• Fine azeurophilic granules are present.
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38. AML-M6(ERYTHROLEUKEMIA)
• Predominant cells in the bone marrow is erythroblast.
• Predominant feature is anemia with striking poikilocytosis and
anisocytosis.
• The diagnosis of erythroleucaemia can be done if more then 50% of
bone marrow cells are erythroid and 30% of remaining are blast.
• True erythro leukemia occurs when BM is replaced by proliferating
normoblast showing no maturation beyond basophilic normoblasts.
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39. PB film in a patient with M6 AML showing an abnormal
circulating erythroblast
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40. AML-M7
 Peripheral blood pancytopenia.
 High peripheral blood blast count.
 Micro megakaryocytes and undifferentiated blast.
 Bone marrow reveals increased fibroblast.
 Showing cytoplasmic budding.
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41. AML-M7 (MEGAKARYOBLASTIC LEUKEMIA)
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44. BETHESDA CONSENSUS
• Sub-classification of AML
• The 2006 International Bethesda Consensus
recommends the following CD markers for the initial
evaluation of myeloid leukemias: CD7, CD11b, CD13,
CD14, CD15, CD16, CD33, CD34, CD45, CD56, CD117,
HLA Dr.
• http://www.clinicsinoncology.com/pdfs_folder/cio-v1-
id1166.pdf
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45. CYTOCHEMICAL FEATURES OF AML
SUBTYPE MPO/SBB SE NSE
AML-M0 _ _ _
AML-M1 + + _
AML-M2 + + _
AML-M3 + + _
AML-M4 + + +
AML-M5a _ _ +
AML-M5b _ _ +
AML-M6 + _ +/_
AML-M7 _ _ Strongly + using acetate
as substrate
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46. WHO CLASSIFICATION (NEWER)
•Incorporates and interrelates
morphology, cytogenetic,
molecular genetics, and
immunologic markers.
•20% blast in blood and bone
marrow.
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47. WHO CLASSIFICATION OF AML
1.Acute myeloid leukemia with recurrent genetic abnormalities
AML with t(8;21)(q22;q22)
Acute promyelocytic leukemias [AML with t(15;17)(q22;q11)
AML with abnormal bone marrow eosinophils inv(16)(p13q22) or
t(16;16)(p13;q11)
AML with 11q23
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48. 2 . AML with multilineage dysplasia
With previous myelodysplastic syndrome
Without previous myelodysplastic syndrome
3. AML & myelodysplastic syndromes, therapy-related
Alkylating agent-related
Topoisomerase type II inhibitor-related (some may be lymphoid)
Other types
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49. 4.AML not otherwise categorized
 AML minimally differentiated
 AML with maturation
 AML without maturation
 Acute myelomonocytic leukemia
 Acute monoblastic and monocytic leukemia
 Acute erythroid leukemia
 Acute megakaryoblastic leukemia
 Acute basophilic leukemia
 Acute panmyelosis with myelofibrosis
5. Acute Biphenotypic Leukemias
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https://onlinelibrary.wiley.com/doi/full/
10.1002/cyto.b.20363
https://onlinelibrary.wiley.com/doi/full/
10.1002/cyto.b.20363
https://wiki.clinicalflow.com/acute-
megakaryoblastic-leukemia-amkl-m7

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