¹Division of Medical and Molecular Genetics, Guy's, King's and St Thomas' School of Medicine and Dept of Haematology, University College London Hospitals, London, UK

²Department of Cellular Biotechnologies and Hematology, Università la Sapienza, Rome, Italy

Correspondence to: D Grimwade, Division of Medical and Molecular Genetics, Guy's, King's and St Thomas' School of Medicine, Cancer Genetics Laboratory, 8th Floor, Guy's Tower, Guy's Hospital, London SE1 9RT, UK; Fax: 020 7 955 8762

Acute promyelocytic leukemia (APL) is characterized by a number of features that underpin the need for rapid and accurate diagnosis and demand a highly specific treatment approach. These include the potentially devastating coagulopathy, sensitivity to anthracycline-based chemotherapy regimens, as well as unique responses to all-trans retinoic acid and arsenic trioxide that have revolutionized therapy over the last decade. The chromosomal translocation t(15;17) which generates the PML-RAR fusion gene has long been considered the diagnostic hallmark of APL; however, this abnormality is not detected in approximately 10% cases with successful karyotype analysis. In the majority of these cases, the PML-RAR fusion gene is still formed, resulting from insertion events or more complex rearrangements. These cases share the beneficial response to retinoids and favorable prognosis of those with documented t(15;17), underscoring the clinical relevance of molecular analyses in diagnostic refinement. In other cases of t(15;17) negative APL, various chromosomal rearrangements involving 17q21 have been documented leading to fusion of RAR to alternative partners, namely PLZF, NPM, NuMA and STAT5b. The nature of the fusion partner has a significant bearing upon disease characteristics, including sensitivity to retinoids and arsenic trioxide. APL has provided an exciting treatment model for other forms of AML whereby therapeutic approach is directed towards cytogenetically and molecularly defined subgroups and further modified according to response as determined by minimal residual disease (MRD) monitoring. Recent studies suggest that rigorous MRD monitoring, coupled with pre-emptive therapy at the point of molecular relapse improves survival in the relatively small subgroup of PML-RAR positive patients with 'poor risk' disease. Advent of 'real-time' quantitative RT-PCR technology seems set to yield further improvements in the predictive value of MRD assessment, achieve more rapid sample throughput and facilitate inter- and intra-laboratory standardization, thereby enabling more reliable comparison of data between international trial groups.

Leukemia (2002) 16, 1959-1973. doi:10.1038/sj.leu.2402721

acute promyelocytic leukemia (APL); RT-PCR; minimal residual disease (MRD); real-time quantitative RT-PCR (RQ-PCR)