1. Acute Myeloid Leukemia
Ali Al Khader, M.D.
Faculty of Medicine
Al-Balqa’ Applied University

3. Overview Originate from transformed hematopoietic progenitors
…due to acquired oncogenic mutations that impede differentiation
…leading to:
Accumulation of immature myeloid forms (blasts) in the bone marrow suppresses normal hematopoiesis
The replacement of the marrow with blasts produces marrow failure and complications related to anemia, thrombocytopenia, and neutropenia

4. Overview, cont’d
Occurs at all ages, but the incidence rises throughout life, peaking after 60 years of age
The current WHO classification subdivides AML into four categories
…see next slide

6. Pathogenesis
Most AMLs harbor mutations in genes encoding transcription factors that are required for
normal myeloid cell differentiation
…defective maturation of early myeloid cells resulting in the accumulation of myeloid
precursors (blasts) in the marrow
Of particular interest is the (15;17) translocation in acute promyelocytic leukemia
…results in the fusion of the retinoic acid receptor α (RARA) gene on chromosome 17 and
the PML gene on chromosome 15
…the chimeric gene produces a PML/RARα fusion protein that blocks myeloid differentiation
at the promyelocytic stage
…probably in part by inhibiting the function of normal retinoic acid receptors
…Pharmacologic doses of all-trans retinoic acid (ATRA), an analogue of vitamin A can be
used…also its combination with arsenic trioxide (a salt that induces the degradation of the
PML/RARA fusion protein) can cure 80% of patients

7. Pathogenesis, cont’d
Some of the other mutations implicated in AML have no effect on differentiation but instead enhance cellular proliferation and survival
…examples: - FLT3, a receptor tyrosine kinase
- RAS

8. Morphology
By definition, in AML myeloid blasts or promyelocytes make up more than 20% of the bone marrow cellular component
Myeloblasts (precursors of granulocytes)
-delicate nuclear chromatin
-three to five nucleoli
-fine azurophilic cytoplasmic granules
-Auer rods, distinctive red-staining rod-like structures..may be present in myeloblasts
or more differentiated cells
…they are particularly numerous in acute promyelocytic leukemia
…Auer rods are specific for neoplastic myeloblasts and thus a helpful diagnostic
clue when present
In other subtypes of AML, monoblasts, erythroblasts, or megakaryoblasts predominate

9. Morphology, cont’d

10. Clinical notes
Splenomegaly and lymphadenopathy generally are less prominent than in ALL
On rare occasions AML mimics a lymphoma by manifesting as a discrete tissue mass (a so-called granulocytic sarcoma)

11. Clinical notes, cont’d
The overall survival in all patients is only 15% to 30% with conventional chemotherapy
t(8,21) and inv16 are good
Hematopoietic stem cell transplantation…sometimes used

12. Diagnosis The diagnosis and classification of AML are based on:
-morphologic
-histochemical
-immunophenotypic
-karyotypic findings
Of these, the karyotype (to detect translocations) is most predictive
of outcome

13. Immunohistochemistry (Immunophenotype of tumor cells)
myeloid-associated antigens:
…CD13, CD14, CD15, CD64, CD117 (cKIT), or CD33

14. Thank You