Minimal Residual Disease in Acute Myeloid Leukemia

Abstract

Acute myeloid leukemia (AML) is a biologically heterogeneous disease of the hematopoietic system characterized by a clonal accumulation of immature myeloid cells in the bone marrow. The management of this disease is clinically complex, with only approx 40% of the patients treated with conventional or highdose chemotherapy reaching a long-term complete remission (CR). Nonrandom chromosomal abnormalities are identified at the cytogenetic level in approx 55% of all adult primary or de novo AML patients and have long been recognized as important independent prognostic indicators for the achievement of CR, duration of first CR, and survival following intensive chemotherapy treatment (1,2). Among these recurrent aberrations, chromosome translocations and inversions often result in genomic structural rearrangements leading to the creation of chimeric fusion genes that, in turn, encode fusion transcripts readily detected in bone marrow (BM) and blood by highly sensitive molecular techniques such as the reverse transcription—polymerase chain reaction (RT-PCR). Because the fusion transcripts are thought to be specific to the leukemic cells, their detection in BM or blood from AML patients who achieve CR following intensive treatment has been used as a surrogate marker for minimal residual disease (MRD) (3–5). It was anticipated that those patients with a positive assay would inevitably relapse as a consequence of the treatment failure to completely eradicate the leukemogenic clone, whereas those patients with a negative RT-PCR status would remain in continuous CR (CCR).