Frequency and dynamics of leukemia-initiating cells during short-term ex-vivo culture informs outcomes in acute myeloid leukemia patients
Authors listEmmanuel Griessinger Fernando Dos Anjos Afonso Jacques Vargaftig David C Taussig François Lassailly Thomas Prebet Véronique Imbert Marielle Nebout Norbert Vey Christian Chabannon Andrew Filby Frederic Bollet-Quivogne John G Gribben Jean-François Peyron Dominique Bonnet
Acute myeloid leukemia (AML) is sustained by a subpopulation of rare leukemia-initiating cells (LIC) detected in the xenograft assay by their capacity to self-renew and to generate non-LICs in vivo The xenotransplantation model captures functional properties of LICs that have clinical prognostic value. However, the long duration of this in vivo assay has hampered its use as a prognostic tool. Here, we show, using an ex vivo coculture system, that intermediate and poor risk AML patient samples at diagnosis have a 5 to 7 times higher frequency of leukemic long-term culture-initiating cells (L-LTC-IC) compared with the good risk group. We defined a fluorescence dilution factor (FDF) parameter that monitors sample proliferation over 1 week and established a strong correlation of this parameter with the L-LTC-IC frequency. A higher FDF was found for poor prognostic AMLs or for samples capable of engrafting NSG mice compared with good risk AMLs or nonengrafters. Importantly, FDF could classify normal karyotype intermediate risk patients into two groups with a significant difference in their overall survival, thus making this nongenetic and non-in vivo approach a new clinically relevant tool for better diagnosis of AML patients. Cancer Res; 76(8); 2082-6. ©2016 AACR.
Journal Cancer Research
Issue number 8