Circulating soluble LR11/SorLA levels are highly increased and ameliorated by chemotherapy in acute leukemias

Abstract

BackgroundLR11/SorLA, a receptor interacting with CD87 on monocytes and macrophages, is highly expressed on human immature hematopoietic stem cells. However, it is unknown whether LR11 is expressed on premature leukemic cells, and whether the levels of circulating soluble LR11 (sLR11) shed from leukemic cells correlate with disease state. MethodsThe expression of LR11 on leucocytes and leukemic cells was examined by flow cytometry. Serum sLR11 levels were measured by ELISA in patients with various hematological diseases, including 43 acute myeloid leukemia (AML) and 23 acute lymphoblastic leukemia (ALL) patients. Data were subjected to statistical analysis for validation of sLR11 levels and patients' clinical data. ResultsLR11 is specifically expressed in monocytes, and surface levels on leukemic cells are highly induced in both AML and ALL. sLR11 levels of acute leukemia patients were significantly increased (P<0.001) (ALL, 73.5±93.5ng/ml; AML, 26.8±29.1ng/ml) in comparison to controls (9.2±3.3ng/ml). Patients with AML and ALL in remission showed significantly decreased sLR11 levels to below 20ng/ml. ConclusionsLR11 and its released soluble form are strongly elevated in acute leukemias. Remarkably, this increase in circulating sLR11 levels is ameliorated at complete remission.