LAUSR

Therapeutic progress in acute myeloid leukemia (AML) has been frustratingly slow over the last four decades. The 5-year overall survival (OS) of AML patients younger than 60 years improved from around 20% in the 1980s to 45% in the first decade of the new millenium. Long-term survival of AML patients is extremely poor. Only 17% of AML patients younger than 60 years and just 2.4% of AML patients older than 60 who had been treated with chemotherapy only are disease free 10 years after diagnosis. However, there has been one exception. Acute promyelocytic leukemia (APML), a subgroup of AML, has seen an improvement in 5-year OS from around 30% in 1989 to more than 95% in 2016. Remarkably, these survival figures were achieved using a chemotherapy-free regimen. It is obvious that our ability to cure APML is based on an in depth understanding of the genetics and biology of APML. Unfortunately, we have come to realize in the last decade that AML is not a single disease entity but a genetically extremely diverse group of malignant diseases affecting the hematopoietic stem cell. In one landmark genomic study of 200 AML samples, 237 genes were found to be mutated in more than one sample. In this special, themed issue, we have attempted to shed light on several aspects of AML and look at this disease from several different angles. These include a look at clonal hematopoiesis and preleukemia by Hartmann and Metzeler, a review about clonal evolution by Vosberg and Greif, and an overview of leukemia stem cells and the cell of origin of leukemia by Chopra and Bohlander. Thoms, Beck, and Pimanda elegantly summarize our knowledge about disturbed transcription factor networks in AML. It is an exciting time in AML treatment and research. Recently, after decades of “playing” around by combining and varying the dosing of unspecific cytotoxic drugs, we have seen the arrival of a plethora of new drugs for AML treatment. Barbosa, Li, Adams, and Deshpande take a look at the disturbances of the TP53 pathway, and Taylor and Lee describe the perturbances of splicing regulation. Both reviews discuss how the changes in the TP53 and the splicing pathways can be leveraged to develop novel treatments. Lastly, a comprehensive, up-to-date overview of new drugs that have recently become available for AML treatment and of new AML treatment strategies is presented by Tiong and Wei. Of course, the topics covered here are far from exhaustive, as can be expected in a fast moving research field. Important areas, like the role of the bone marrow microenvironment or the current status of immunotherapy in AML is not covered. Nevertheless, we hope that you will enjoy reading this collection of review articles and that it will inspire you to develop new ideas and concepts that will promote our understanding of AML biology and eventually lead to a cure for this disease. We especially want to thank all the authors and reviewers for their efforts to write and review these articles and for sharing their valuable insights and expertise.