3. Acute Leukemias
Characteristics
1. malignant transformation of a hematopoietic stem cell
2.rapid progressive
3.fetal without treatment
4.replacement of normal bone marrow by blast cells
5. Blast cells consist 90% of B.M and P. blood
6.Occurs in all ages
7. Clinical onset is sudden
8.Anemia and thrombocytopenia are mild to severe
9.WBC is variable (high, normal or low)
10.Organomegaly is mild
4. LABORATORY DIAGNOSIS of acute leukemias panel
1-Complete blood picture
-Anaemia
-White cell count
-Platelet count
2-Bone marrow examination -
Cellularity
-% of blasts
3-Cytochemical stains
e.g Myeloperoxidase, Sudan black B
4-Immunophenotyping
A panel of monoclonal antibodies
(CDs) are used to detect : myeloid
markers and lymphoid
markers (for B & T cells).
5-Genetic Analysis (karyotyping,
FISH and PCR)
Chromosomal analysis is important for the
diagnosis , classification and follow up of
haematologic malignancies.
5. Types of acute leukemia
1. Acute myelogenous leukemia (AML).
2. acute lymphoblastic leukemia (ALL)
3. Acute Myelomonocytic leukemia(AMML)
Site of leukemic cells accumulation
They can infiltrate any organ or site
1-Bone marrow--- replace normal hematopoietic cells
2-Liver and spleen, lymph nodes
3-CNS, Kidneys and gonads
What occurs in these sites?
1-CNS function disorder
2-Bone marrow :
a) impaired normal cells production (RBC, WBC, PLTs)
b) Production of immature (blast) cells
6. Acute Myeloblastic Leukemia
AML is a malignant, clonal disease that involves proliferation of
blasts.
AML is:
1. It is a blood cancer
2. Failure to produce normal cells (Neutrophil etc)
3. Highly heterogeneous
4. Mostly in adult
5. Belong to myeloid group cancer mainly Neutrophils
6. There is no enough Neutrophils for bacteria killing
Bone
marrow
peripheral
Blood
Involved in
7. FAB classification
FAB CLASSIFICATION
Morphologic classification of AML is based on
1. Cellular differentiation ( What type of cell?) (granulocyte, monocyte ,
erythroid, or megakaryocytic)
2. Extent of maturation (Myeloblast, promyelocyte, granulocyte)
1. M0 Minimally differentiated
2. M1 Myeloblastic
3. M2 Myeloblastic with differentiation.
4.M3 Promyelocytic
5. M4 Myelomonocytic
6.M5 Monoblastic
7. M6 Erythroleukemia
8.M7 Megakaryocytic
9. Pathophysiology
Uncontrolled growth of blasts in marrow leads to
1. Stop normal cells production .
2. Appearance of blasts in peripheral blood.
3. Accumulation of blasts in other sites (CNS, Kidney , Liver, spleen).
4.Function disorders of many organs.
Metabolic effects of AML
1. Increase in uric acid ––>uric acid nephropathy
2. Release of phosphates ––> decrease in Ca2+and Mg2+
10. Patient`s Symptoms (Clinical Features of AML)
1.Anemia (weakness, fatigue, dyspnea on exertion)
2.Bleeding (mucosal bleeding, purpura)
3.Infection (neutropenia ––> infections
AML in brief
Cells defect: granular cells (Neutrrophils,Eosino.
Basophil, Monocyte)
Origin: Bone marrow
Age of patient: adult
11. Acute leukemia cause morbidity and
mortality through :-
1. Deficiency in blood cell
number and function
2. Invasion of vital organs
3. Systemic disturbances by
metabolic imbalance
12. 1-CBC Result
1-anemia (low Hb, PCV, RBC
2-Thrombocytopenia
3--WBC
Blood smear study
•RBC: Normocytic anemia
•PLTs:Low count - <10x109/l
•WBC:
•myeloblast 90%
•neutropenia
•Normal other cells 10%
•presence of Auer rods
presence of abnormal white
blood cells
<1.0x109/l to >200x109/l,
1. Normal count
2. Lower count
3. Higher count +
50% of patient has >100.000/cum
AML_Laboratory findings
13. Flowcytometry or immunophenotypinag AML
diagnosis
identify antigens present on the blast cells
Positive for
CD 13
CD 33
====
HLA-DR
CD34
Indication of AML
Indication of stem cells
14. 2-Bone marrow aspirate-and biopsy
myeloblast is the predominant cell
Decrease in normal
1. erythropoiesis,
2. myelopoiesis,
3. megakaryocytes
15.
16. 3-cytochemistery staining
1-Sudan black stain (SBB): Positive
2-Myeloperoxidase stain: (MPO): Positive
3- Specific Esterase (ES): Positive
Positive: MPO
Positive: ES
