Quantitative Analysis of AML1-ETO Fusion Transcripts in t(8;21) Positive AML Using Real-Time RT-PCR

Abstract

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy that requires urgent cytostatic treatment. The incidence of AML is approximately 2–4 new cases per 100,000 with a median age of about 65 years. Despite intensive treatment with cytotoxic drugs and bone marrow transplantation, long-term survival is less than 30% [1, 2]. In AML an early progenitor is transformed to a leukemic blast that proliferates in blood and bone marrow and suppresses normal hematopoiesis. In about 55% of cases the leukemic blasts show cytogenetic abnormalities that may be associated with distinct biological and clinical features. These specific cytogenetic abnormalities can be detected via laboratory techniques like classical cytogenetics, FISH, Southern blotting or PCR. The specific karyotype of the leukemic clone is not only one of the most important prognostic factors in AML, but it also facilitates monitoring of minimal residual disease at times of cytomorphologic remission when leukemic blasts may be undetectable by light microscopy. At primary diagnosis the estimated leukemic burden is about 10¹² malignant cells. Complete remission after chemotherapy is defined as the return to normal bone marrow cytomorphology with less than 5% myeloid blasts. However, in the state of cytomorphologic remission patients may still have 10¹⁰ leukemic blasts and relapse is a common cause of treatment failure [4]. The kinetics of leukemic regrowth and host factors like the immune response that influence residual leukemia remain largely unknown.