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 preemptive 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 intralaboratory standardization, thereby enabling more reliable comparison of data between international trial groups. Leukemia (2002Leukemia ( ) 16, 1959Leukemia ( -1973
Clinical featuresAcute promyelocytic leukemia (APL) is associated with a number of features that emphasize the need for rapid and accurate diagnosis and demand a highly specific treatment approach. Of critical importance is the potentially severe coagulopathy that often accompanies the disease, which can induce thrombotic and more often hemorrhagic complications, that are the most prevalent clinical features at presentation. The coagulopathy is frequently triggered or further exacerbated by initiation of chemotherapy, and led to the demise of up to a quarter of patients in early studies. However, increased awareness of this problem, prompt initiation of ATRA-based therapy, together with improvements in supportive care have seen a reduction in induction death rates to approximately 10% or less in more recent clinical studies.