ACUTE MYELOGENOUS LEUKEMIA (AML)

Tesoro, Willianne C.

DMD-2D

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.

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.

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.

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

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

PATIENTS WITH AML

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.

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.