acute leukemia, acute myeloblastic leukemia, acute lymphoblastic leukemia, WHO classification

1. LEUKEMIAS
Acute leukemias

2. What you will learn now?
 Definition
 Types
 Differences between myloblasts and
lymphoblasts
 Pathogenesis( leukemogenesis)
 Morphology
 Clinical features
 Lab findings

3. Leukemias are the group of disorders
characterized by malignant transformation of
the blood forming cells
 It may involve any of the cell lines or a stem cell
common to several cell lines.

4.  Leukemias are classified into 2 major groups
Acute Onset is usually rapid,
The disease is very aggressive,
The cells involved are usually poorly
differentiated with many blasts.
Chronic Onset is insidious,
The disease is usually less aggressive,
The cells involved are usually more mature
cells

5.  Both acute and chronic leukemias are further classified
according to the prominent cell line involved in the
expansion:
 If the prominent cell line is of the myeloid series it is a
MYELOCYTIC LEUKEMIA (sometimes also
called granulocytic)
 If the prominent cell line is of the lymphoid series it is
a LYMPHOCYTIC LEUKEMIA

6.  Therefore, there are four basic types of
leukemia
 Acute myelocytic leukemia – AML
 Acute lymphocytic leukemia – ALL
 Chronic myelocytic leukemia – CML
 Chronic lymphocytic leukemia – CLL

7. Etiology
 the exact cause is frequently not known, but
predisposing factors are known
 Host factors
 Environmental factors

8. Etiology
 the exact cause is frequently not known, but
predisposing factors are known
 Host factors
 Some individuals have an inherited increased
predisposition to develop leukemia
 There is an increased incidence in those with an
inherited tendency for chromosome fragility or
abnormality or those with increased numbers of
chromosomes (such as Down’s syndrome). Many of
these diseases are characterized by chromosomal
translocations.

9.  There is an increased incidence in those with
hereditary immunodeficiencies.
 There is an increased incidence in those with
chronic marrow dysfunction such as those
with myeloproliferative diseases,
myelodysplastic syndromes, aplastic anemia, or
paroxsymal nocturnal hemoglobinuria.

10.  Environmental factors:
 Exposure to ionizing radiation
 Exposure to mutagenic chemicals and drugs
 Viral infections

11. Incidence
 Acute leukemias can occur in all age groups
 ALL is more common in children
 AML is more common in adults
 Chronic leukemias are usually a disease of
adults
 CLL is extremely rare in children and unusual
before the age of 40
 CML has a peak age of 30-50

12.  Comparison of acute and chronic
leukemias:
Acute Chronic
Age all ages usually adults
Clinical onset sudden insidious
Course (untreated) 6 mo. or less 2-6 years
Leukemic cells immature >20% blasts more mature
` cells
Anemia prominent mild
Thrombocytopenia prominent mild
WBC count variable increased
Lymphadenopathy mild present;often
prominent
Splenomegaly mild present;often
prominent

13. Acute leukemia - pathogenesis
 Is a result of:
 Malignant transformation of a stem cell leading to
unregulated proliferation and
 Arrest in maturation at the primitive blast stage.
Remember that a blast is the most immature cell that can
be recognized as committed to a particular cell line.

14.  Leukemic proliferation, accumulation, and invasion of
normal tissues, including the liver, spleen, lymph nodes,
central nervous system, and skin, cause lesions ranging
from rashes to tumors.
 A humoral mediator from the leukemic cells may inhibit
proliferation of normal cells.
 Failure of the bone marrow and normal hematopoiesis may
result in pancytopenia with death from hemorrhaging and
infections.

15. Acute leukemias
 AML and ALL
 FAB classification
AML( 8 subtypes M0 to M7 )
ALL ( L1 to L3 )

16. Myeloblasts with auer rods
the MYELOBLAST is a
large blast with a
moderate amount of
cytoplasm,
fine lacey chromatin, and
prominent nucleoli.
10-40% of myeloblasts
contain auer rods

17. Lymphoblast
in contrast to the
myeloblast, the
LYMPHOBLAST is a
small blast with
scant cytoplasm,
dense chromatin,
indistinct nucleoli, and
no auer rods

19. Cytochemical stains
1. Myeloperoxidase
2. Sudan black
3. Periodic acid
schiff(PAS)
4. Non specific
esterase
5. Acid phosphatase
1. Myeloblasts( except M0)
2. Immature cells in AML
3. Lymphoblasts ,
erythroblasts
4. Monocytic ( M4 M 5)
5. Monocytic cells and
focally in lymphoblasts

20. FAB Acute Myeloid Leukemia
M0 Minimally differentiated AML 5% - 10%
Negative or < 3% blasts stain for MPO ,PAS and NSE
blasts are negative for B and T lymphoid antigens, platelet
glycoproteins and erythroid glycophorin A.
M1 Myeloblastic without maturation 10 - 20%
>90% cells are myeloblasts
3% of blasts stain for MPO
+8 frequently seen

21. M2 AML with maturation
30 - 40%
30% - 90% are myeloblasts
~ 15% with t(8:21)

22. M3 Acute Promyelocytic
Leukemia (APML)
10-15%
Auer rods/ faggot cells may be
seen
Granules contain procoagulants
(thromboplastin-like) - massive
DIC
t(15:17) is diagnostic

23. M4 Acute
Myelomonocytic
Leukemia 10-15%
Incresed incidence CNS
involvement
Monocytes and
promonocytes 20% -
80%

24. M5a Acute Monoblastic
Leukemia 10-15%
M5b AMoL with
differentiation <5%
Often asso with infiltration
into gums/skin
Weakness, bleeding and
diffuse erythematous
skin rash

25. M6 Erythroleukemia (Di
Guglielmo) <5%
50% or more of all
nucleated marrow cells
are erythroid precursors,
and 30% or more of the
remaining nonerythroid
cells are myeloblasts

26. M7 Acute
Megakaryoblastic
Leukemia
<5%
Assoc with fibrosis

27. FAB Acute Lymphoblastic
Leukemia
Acute lymphoblastic
leukemia
L-1 85%
L-2 14%
L-3 (Burkitt's)1% childhood

28. ALL L1
Homogenous small
lymphoblasts
Scant cytoplasm
Regular round
nuclei
Inconspicuous
nucleoli

29. ALL L2
Heterogenous
lymphoblasts
Variable cytoplasm
Cleft nuclei
Large nucleoli

30. ALL L3
Homogenous large
lymphoblasts
Vacuolated
cytoplasm
Round nuclei

31. Clinical features
Bone marrow failure Organ infiltration
1. Pallor, lethargy,
dyspnea
2. Bleeding
manifestations
3. Infections
4. fever
1. Pain & tenderness of
bones
2. Lymphadenopathy
3. Hepatosplenomagaly
4. Gum hypertrophy
5. Chloromas
6. Meningeal signs

32. Lab findings
1. Blood picture
RBC
WBC
Platelets
2. Bone marrow
3. Cytochemistry
4. Cytogenetics

33. FAB vs WHO Classifications of
Hematologic Neoplasm
 FAB criteria
 Morphology
 Cytochemistry
 WHO criteria
 Morphology
 Immunophenotyping
 Genetic features
 Karyotyping
 Molecular testing
 Clinical features

34. WHO Classification of AML
 AML with recurrent cytogenic translocations
 AML with multi-lineage dysplasia
 AML and myelodysplasia, therapy related
 AML, not otherwise categorized

36. Summary
 Definition
 Types
 Differences between myloblasts and
lymphoblasts
 Pathogenesis( leukemogenesis)
 Morphology
 Clinical features
 Lab findings
 WHO classification

37. Thank you