Contributed by Isil Z Yildiz, MD and Lydia C. Contis, MD FINAL DIAGNOSIS
Acute Myeloid Leukemia (AML) with t(8;21) (q22;q22); RUNX1-RUNX1T1.
CLINICAL COURSE
The patient remained in sepsis and critically ill, requiring prone positioning to maintain her ventilatory status and depending on vasopressors for cardiovascular stabilization. She received multiple red blood cell and platelet transfusions. She was treated with multiple antibiotics for bilateral pneumonia. Further imaging studies could not be performed given her critically ill state. She also required hemodialysis as she developed acute kidney injury secondary to acute tubular necrosis. She was taken for emergent head computerized tomography when her pupils were noted to be fixed and dilated. Head computerized tomography showed a large middle cerebral artery infarct with global diffuse injury and transtentorial herniation. She was pronounced dead due to stroke secondary to acute leukemia as the preliminary cause of death.
DISCUSSION
AML with t(8;21) (q22;q22); RUNX1-RUNX1T1 is subclassified within the acute myeloid leukemia (AML) with recurrent genetic abnormalities WHO classification of AML . It is defined by the presence of the translocation, a variant translocation or molecular RUNX1-RUNX1T1 fusion, regardless of blast count. It comprises approximately 5% of all AML and is seen predominantly in younger patients (1).
Acute myeloid leukemia with t(8;21)(q22;q22) is usually associated with a good response to chemotherapy and a high complete remission rate with long-term disease-free survival when treated with high dose cytarabine in the consolidation phase. Some factors appear to adversely affect prognosis including CD56 expression and the presence of KIT mutation (1).
Morphology
The common morphological features include the presence of large blasts with abundant basophilic cytoplasm, often containing numerous azurophilic granules and perinuclear clearing (hofs). Auer rods are frequently found and appear as a single long and sharp rod with tapered ends.Additional distinctive findings include salmon-colored cytoplasm with a rim of basophilia in maturing granulocytes, and dysplastic features of the mature granulocytes (1, 2).
Circulating blasts accompanied by cytopenias are common in peripheral blood. In the bone marrow, the blast count is variable and in some cases is less than the otherwise required 20%. In these cases, the presence of (8;21)(q22;q22) translocation allows for a diagnosis of AML. The bone marrow biopsy is hypercellular with evidence of granulocytic maturation (1,2).
Immunophenotype
The characteristic immunophenotypic profile of AML with the (8;21)(q22;q22) translocation display a characteristic immunophenotype with a subpopulation of blast cells showing high intensity expression of CD34, together with HLA-DR, myeloperoxidase (MPO) and CD13, but relatively weak expression of CD33.There are usually signs of granulocytic differentiation with subpopulations of cells showing granulocytic maturation demonstrated by CD15 and/or CD65 expression. CD56 is expressed in a fraction of cases and may have adverse prognostic significance. Diminished CD19 and positive CD56 expression on the leukemic blasts may suggest an accompanying underlying KIT activating mutation (1, 2).
Genetics
The t(8;21)(q22;q22) translocation is one of the most frequent recurrent chromosomal abnormalities in adult de novo AML, seen in about 6% of patients. The rearrangement disrupts the RUNX1 gene on chromosome 21 that codes for subunit alpha of core-binding factor and leads to the formation of a chimeric gene, RUNX1-RUNX1T1, also called AML1/ETO. The presence of this cytogenetic abnormality or gene rearrangement is associated with AML with maturation in the neutrophil lineage (FAB M2). The fusion protein represses the transcription of the p14ARF tumor suppressor gene, leading to knockout of the p53 pathway in these cells, blocking cellular growth arrest or apoptosis in response to activated oncogenes, and immortalizing hematopoietic progenitor/leukemia cells (3).
REFERENCES
Contributed by Isil Z Yildiz, MD and Lydia C. Contis, MD
  |
