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Floeth, Matthias; Elges, Sandra; Gerss, Joachim; Schwoeppe, Christian; Kessler, Torsten; Herold, Tobias; Wardelmann, Eva; Berdel, Wolfgang E.; Lenz, Georg; Mikesch, Jan-Henrik; Hartmann, Wolfgang; Schliemann, Christoph; Angenendt, Linus (2020): Low-density lipoprotein receptor (LDLR) is an independent adverse prognostic factor in acute myeloid leukaemia. In: British Journal of Haematology, Vol. 192, No. 3: pp. 494-503
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Abstract

The low-density lipoprotein receptor (LDLR) is a membrane receptor that mediates the endocytosis of low-density lipoprotein (LDL). Uptake of LDL has been proposed to contribute to chemotherapy resistance of acute myeloid leukaemia (AML) cell lines in vitro. In the present study, we analysed LDLR expression and survival using bone marrow biopsies from 187 intensively treated patients with AML. Here, increasing LDLR expression was associated with decreasing overall (58 center dot 4%, 44 center dot 2%, and 24 center dot 4%;P = 0 center dot 0018), as well as event-free survival (41 center dot 7%, 18 center dot 1%, and 14 center dot 3%;P = 0 center dot 0077), and an increasing cumulative incidence of relapse (33 center dot 9%, 55 center dot 1%, and 71 center dot 4%;P = 0 center dot 0011). Associations of LDLR expression with survival were confirmed in 557 intensively treated patients from two international validation cohorts. In the analytic and validation cohorts, LDLR expression remained associated with outcome in multivariable regression analyses including the European LeukemiaNet genetic risk classification. Thus, LDLR predicts outcome of patients with AML beyond existing risk factors. Furthermore, we found low expression levels of LDLR in most healthy tissues, suggesting it as a promising target for antibody-based pharmacodelivery approaches in AML.