2. ACUTE MYELOGENOUS LEUKEMIA
(AML) is a clonal hematopoietic disorder resulting
from genetic alterations in normal hematopoietic
stem cells.
These changes alter normal hematopoietic growth
and differentiation, resulting in an accumulation of
large numbers of abnormal, immature myeloid cells
in the bone marrow and peripheral blood.
These cells are capable of dividing and
proliferating, but cannot differentiate into mature
hematopoietic cells.
AML is more common in men than women.
AML is the most common acute leukemia affecting
adults, and its incidence increases with age.
3. PATHOGENESIS
The malignant cell in AML is the myeloblast.
In normal hematopoiesis, the myeloblast is an
immature precursor of myeloid white blood cells; a
normal myeloblast will gradually mature into a
mature white blood cell.
In AML, though, a single myeloblast accumulates
genetic changes which "freeze" the cell in its
immature state and prevent differentiation.
4.
5.
6. CHROMOSOMAL TRANSLOCATION
The translocation fuses
the AML1 gene (also called
RUNX1) on chromosome 21
with the ETO gene (also
referred to as the RUNX1T1
gene that encodes the
CBFA2T1 protein) on
chromosome 8.
CBFA2T1 protein - This
protein has multiple effects
on the regulation of the
proliferation, the
differentiation, and the
viability of leukemic cells.
7. Bone marrow smear from a 23-year-old female with acute myeloblastic
leukemia with maturation associated with a t(8;21) chromosome abnormality.
The numerous myelocytes have abundant cytoplasm with prominent
specific granulation. One of the myeloblasts to the left of center contains
a prominent Auer rod.
*AUER ROD - are clumps of azurophilic granular material that form
elongated needles seen in the cytoplasm of leukemic blasts
8. SIGNS AND SYMPTOMS
Epistaxis
Bleeding gums
Bruising/contusions
Bone pain or tenderness
Fatigue
Fever
Heavy menstrual periods
Pallor
Shortness of breath (gets worse with exercise)
Skin rash or lesion
Swollen gums (rare)
Weight loss
10. DIAGNOSIS
Physical exam
CBC(Complete Blood Count) -
Peripheral blood smear- A procedure in which a sample of blood is checked for blast
cells, the number and kinds of white blood cells, the number of platelets, and changes in
the shape of blood cells.
Bone marrow aspiration and biopsy - The removal of bone marrow, blood, and a small
piece of bone by inserting a hollow needle into the hipbone or breastbone.
Cytogenetic analysis: A laboratory test in which the cells in a sample of blood or bone
marrow are viewed under a microscope to look for certain changes in the chromosomes.
Other tests, such as fluorescence in situ hybridization (FISH), may also be done to look
for certain changes in the chromosomes.
11. TREATMENT
First phase: Remission Induction
Chemotherapy - The goals of induction
chemotherapy are to eliminate leukemia
cells from the blood and bone marrow
and to induce a remission. A complete
remission is defined as having no visible
leukemia cells in the blood or bone
marrow and having normal blood counts
without the need of transfusions.
Second Phase: Consolidation
Chemotherapy - Once a patient
achieves a complete remission more
chemotherapy is needed to destroy any
residual leukemia in the body.
Consolidation chemotherapy can consist
of the following:
a) Additional cycles of intensive
chemotherapy.
b) A bone marrow transplant/stem cell
transplant using one's own blood or
marrow, called an autologous transplant.
c) A bone marrow transplant/stem cell
transplant using blood or marrow from a
donor, such as a brother or sister or
unrelated person. This is called an
allogeneic transplant.