Exp Hematol. 2017 Dec 15. pii: S0301-472X(17)30900-1. doi: 10.1016/j.exphem.2017.12.002. [Epub ahead of print]

Acute myeloid leukemia xenograft success prediction: saving time.

Griessinger E¹, Vargaftig J², Horswell S³, Taussig DC⁴, Gribben J⁵, Bonnet D⁶.

Abstract

Xenograft assay allows the functional analysis of Leukemia Initiating Cells (LICs) of acute myeloid leukemia (AML) primary samples. However 40% of samples derived from better outcome patients, fail to engraft immunodeficient mice recipient when following conventional protocols. At diagnosis, the engraftment of intermediate risk group samples cannot be anticipated. In this study, we decided to further explore the reasons of the xenograft success or failure. No differences of extracellular phenotype nor of apoptosis or in cell cycle profile could distinguish samples engrafting (E) from samples non-engrafting NSG mice (NE). Ex-vivo long-term culture assay (LTC) also showed after five weeks a lower content in Leukemic-LTC-Initiating Cells for the NE samples associated with a lower expansion rate capacity. One-week co-cultures with mesenchymal or osteoblastic or endothelial cells did not influence proliferation rate suggesting that E and NE samples are genuinely fast or slow expanding independently of external cue. Consistently engraftment success for some NE samples was observed when analyzing recipient mice six-month later than the conventional three-month period. Eventually we implemented a flow cytometry-based assay, which allow predicting in one week the fast or delayed engraftment potential of a non-characterized Acute Myeloid Leukemia (AML) sample. This approach will be especially useful for selecting intermediate risk group patient samples and for restricting the experimental duration to a three-month period and eventually to reduce the number of animals, the cost and the effort of unnecessary xenograft failures.