Patients with acute promyelocytic leukemia (APL) often present with potentially lifethreatening
hemorrhagic diathesis. The underlying pathomechanisms of APLassociated
coagulopathy are complex. However, two pathways considered to be APLspecific
had been identified: 1) annexin A2 (ANXA2)-associated hyperfibrinolysis and 2)
podoplanin (PDPN)-mediated platelet activation and aggregation. In contrast, since
disseminated intravascular coagulation (DIC) is far less frequent in patients with non-
APL acute myeloid leukemia (AML), the pathophysiology of AML-associated hemorrhagic
disorders is not well understood. Furthermore, the potential threat of coagulopathy in non-
APL AML patients may be underestimated. Herein, we report a patient with non-APL AML
presenting with severe coagulopathy with hyperfibrinolysis. Since his clinical course
resembled a prototypical APL-associated hemorrhagic disorder, we hypothesized
pathophysiological similarities. Performing multiparametric flow cytometry (MFC) and
immunofluorescence imaging (IF) studies, we found the patient’s bone-marrow
mononuclear cells (BM-MNC) to express ANXA2 - a biomarker previously thought to be
APL-specific. In addition, whole-exome sequencing (WES) on sorted BM-MNC (leukemiaassociated
immunophenotype (LAIP)1: ANXAlo, LAIP2: ANXAhi) demonstrated high intratumor
heterogeneity. Since ANXA2 regulation is not well understood, further research to
determine the coagulopathy-initiating events in AML and APL is indicated. Moreover,
ANXA2 and PDPN MFC assessment as a tool to determine the risk of life-threatening DIC
in AML and APL patients should be evaluated.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:84358 |
| Date | 28 March 2023 |
| Creators | Ruhnke, Leo, Stölzel, Friedrich, Wagenführ, Lisa, Altmann, Heidi, Platzbecker, Uwe, Herold, Sylvia, Rump, Andreas, Schröck, Evelin, Bornhäuser, Martin, Schetelig, Johannes, von Bonin, Malte |
| Publisher | Frontiers Research Foundation |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 2234-943X, 666014 |
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