title: Frequency and Dynamics of Leukemia-Initiating Cells during Short-term Ex Vivo Culture Informs Outcomes in Acute Myeloid Leukemia Patients.
abstract: 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.
authors.affiliation: INSERM U1065, C3M, Team 4, Inflammation, Cancer, Cancer Stem Cells, Nice, France. Cancer Research UK, London Research Institute, The Francis Crick Institute, London, United Kingdom. dominique.bonnet@crick.ac.uk Emmanuel.GRIESSINGER@unice.fr.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Griessinger
authors.affiliation: Haematopoeitic Stem Cell Laboratory, The Francis Crick Institute, London, United Kingdom.
authors.forename: Fernando
authors.initials: F
authors.lastname: Anjos-Afonso
authors.affiliation: Cancer Research UK, London Research Institute, The Francis Crick Institute, London, United Kingdom.
authors.forename: Jacques
authors.initials: J
authors.lastname: Vargaftig
authors.affiliation: Centre of Haemato-Oncology, Cancer Research UK Clinical Centre, Barts Cancer Institute, St Bartholomew's Hospital, Queen Mary University of London, London, United Kingdom.
authors.forename: David C
authors.initials: DC
authors.lastname: Taussig
authors.affiliation: Cancer Research UK, London Research Institute, The Francis Crick Institute, London, United Kingdom.
authors.forename: François
authors.initials: F
authors.lastname: Lassailly
authors.affiliation: Haemato-Oncology Division, Paoli-Calmette Institute, Marseille, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Prebet
authors.affiliation: INSERM U1065, C3M, Team 4, Inflammation, Cancer, Cancer Stem Cells, Nice, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Imbert
authors.affiliation: INSERM U1065, C3M, Team 4, Inflammation, Cancer, Cancer Stem Cells, Nice, France.
authors.forename: Marielle
authors.initials: M
authors.lastname: Nebout
authors.affiliation: Haemato-Oncology Division, Paoli-Calmette Institute, Marseille, France.
authors.forename: Norbert
authors.initials: N
authors.lastname: Vey
authors.affiliation: Haemato-Oncology Division, Paoli-Calmette Institute, Marseille, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Chabannon
authors.affiliation: FACS Services, The Francis Crick Institute, London, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Filby
authors.affiliation: Neurophysiology Laboratory, Faculty of Medicine, Brussels University, Brussels, Belgium.
authors.forename: Frederic
authors.initials: F
authors.lastname: Bollet-Quivogne
authors.affiliation: Centre of Haemato-Oncology, Cancer Research UK Clinical Centre, Barts Cancer Institute, St Bartholomew's Hospital, Queen Mary University of London, London, United Kingdom.
authors.forename: John G
authors.initials: JG
authors.lastname: Gribben
authors.affiliation: INSERM U1065, C3M, Team 4, Inflammation, Cancer, Cancer Stem Cells, Nice, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Peyron
authors.affiliation: Cancer Research UK, London Research Institute, The Francis Crick Institute, London, United Kingdom. Haematopoeitic Stem Cell Laboratory, The Francis Crick Institute, London, United Kingdom. dominique.bonnet@crick.ac.uk Emmanuel.GRIESSINGER@unice.fr.
authors.forename: Dominique
authors.initials: D
authors.lastname: Bonnet
mesh_terms: D049109:Cell Proliferation / Q000502:physiology; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D008297:Male; D014411:Neoplastic Stem Cells / Q000473:pathology*; D011379:Prognosis; D014407:Tumor Cells, Cultured