2. ACUTE LEUKEMIA'S
Tanveer Tara SUIT
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.
Tanveer Tara SUIT
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.
Tanveer Tara SUIT
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.
Tanveer Tara SUIT
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
Tanveer Tara SUIT
12. INFILTRATION OF TISSUES/ORGANS
• Enlargement of liver, spleen, lymph nodes
• Gum hypertrophy
• Bone pain
• Other organs: CNS, skin, testis, any organ
Tanveer Tara SUIT
13. • Accumulation of blasts in
microcirculation with impaired
perfusion.
• Lungs: hypoxemia, pulmonary
infiltrates
• CNS: stroke
• Fever and sweats………… common
• Weight loss ……………less common
Tanveer Tara SUIT
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
Tanveer Tara SUIT
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.
Tanveer Tara SUIT
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.
Tanveer Tara SUIT
19. Tanveer Tara SUIT
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.
Tanveer Tara SUIT
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
Tanveer Tara SUIT
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.
Tanveer Tara SUIT
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.
Tanveer Tara SUIT
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.
Tanveer Tara SUIT
26. PB film of a patient with M1 AML showing blasts, some of which
are heavily vacuolated
Tanveer Tara SUIT
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.
Tanveer Tara SUIT
28. BM film of a patient with M2 AML showing unusually
heavy granulation of neutrophils and precursors
Tanveer Tara SUIT
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.
Tanveer Tara SUIT
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.
•
Tanveer Tara SUIT
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.
Tanveer Tara SUIT
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 .
Tanveer Tara SUIT
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.
Tanveer Tara SUIT
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.
Tanveer Tara SUIT
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.
Tanveer Tara SUIT
39. PB film in a patient with M6 AML showing an abnormal
circulating erythroblast
Tanveer Tara SUIT
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
Tanveer Tara SUIT
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
Tanveer Tara SUIT
46. WHO CLASSIFICATION (NEWER)
•Incorporates and interrelates
morphology, cytogenetic,
molecular genetics, and
immunologic markers.
•20% blast in blood and bone
marrow.
Tanveer Tara SUIT
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
Tanveer Tara SUIT
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
Tanveer Tara SUIT
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
Tanveer Tara SUIT