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Acute myeloid leukemia

Revisiting thrombocytopenia in acute promyelocytic leukemia

Leukemia volume 32, pages 1477–1478 (2018)Cite this article

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Acute promyelocytic leukemia (APL), which accounts for 10–15% of acute myeloid leukemia (AML) cases, is one of the true success stories in oncology, as targeted therapeutic approaches have converted this former lethal disease into a disease from which the vast majority of patients is cured. Historically, this unique and highly lethal leukemia subtype was characterized by fatal bleeding events as documented by early studies in the 1950s with median survival rates often below 1 month [1]. This progress in the clinical management of APL would not have been possible without a tremendous progress in understanding the underlying biology of this distinct leukemia subtype, which paved the way for developing oncoprotein—targeted approaches [2]. Recent clinical trials have shown excellent results for low- or intermediate-risk APL patients receiving a chemo-free combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) with an event-free survival and overall survival at 50 months of 97.3% and 99.2%, respectively [3]. However, especially in high risk, as well as frail patients APL still bears considerable early mortality through hemorrhagic complications caused by the development of a coagulopathy [4]. The risk of early death from hemorrhage has been estimated at 5–29% and contributing factors are abnormal coagulation parameters, including a prolonged prothrombin time, partial thromboplastin time, decreased fibrinogen levels, as well as thrombocytopenia. Thrombocytopenia is frequently found in APL patients and together with the white blood cell count determines the risk group [5]. Despite the clinically well-documented coagulopathy and the underlying molecular mechanisms of thrombocytopenia, caused by APL cells are not fully understood.

In this issue of Leukemia, Lavallée et al. [8] reported on intriguing findings, characterizing Podoplanin (PDPN), a gene involved in platelet aggregation, as a protein specifically expressed in human APL and being able to cause thrombocytopenia and prolonged bleeding time in a xenograft model of human AML cell lines.

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Funding

F.K. was supported by grants from the Deutsche Krebshilfe grant 109420 (Max-Eder program); fellowship 2010/04 by the European Hematology Association; and by the Deutsche Forschungsgemeinschaft (DFG) (SFB 1074, project A5) and the Wilhelm Sander Stiftung (2015.153.1). C.B. is supported by grants by the Deutsche Forschungsgemeinschaft (DFG) (SFB 1074, project A4 and SFB 1279 project B1 and C6).

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  1. Department of Internal Medicine III, University Hospital Ulm, Ulm, 89081, Germany

    Florian Kuchenbauer

  2. Comprehensive Cancer Centre Ulm, Institute of Experimental Cancer Research, University Hospital Ulm, Ulm, 89081, Germany

    Christian Buske

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  1. Florian Kuchenbauer
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Correspondence to Florian Kuchenbauer or Christian Buske.

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Kuchenbauer, F., Buske, C. Revisiting thrombocytopenia in acute promyelocytic leukemia. Leukemia 32, 1477–1478 (2018). https://doi.org/10.1038/s41375-018-0105-1

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