Page 19 - Haematologica June

Editorials
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9. Ott CJ, Kopp N, Bird L, et al. BET bromodomain inhibition targets both
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NSG-S mice for acute myeloid leukemia, yes. For myelodysplastic syndrome, no.
Emmanuel Griessinger,1,2 Michael Andreeff3,4
1INSERM U1065, Mediterranean Centre for Molecular Medicine (C3M), Team 4 Leukemia: Molecular Addictions, Resistances & Leukemic Stem Cells, Nice, France; 2Faculté de Médecine, Université de Nice Sophia Antipolis, France; 3Section of Molecular Hematology and Therapy, Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA and 4Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX, USA
E-mail: emmanuel.griessinger@gmail.com or mandreef@mdanderson.org doi:10.3324/haematol.2018.193847
Research on primary patient cells is a compelling chal- lenge for scientists. Although initially limited to short experiments over hours or days, engrafting these primary human cells in immunodeficient mice today allows even more informative investigation to be carried out over weeks and months. This experiment is fascinat- ing, probably first because it gives rise to personal and moral questions about the patient’s avatar. Also, in basic research, the xenograft is the model to be used to reveal the stemness properties of a certain population of cancer cells.1 Although today there are some ex vivo alternatives, the xenograft remains the gold standard technique to study cancer stem cells which are responsible for cancer initiation propagation, maintenance and evolution. Uncovering the presence of primary human leukemic cells in a sample of mouse tissue 10-16 weeks after injection, demonstrating the initial engraftment of leukemia initiating cells (LICs) causes an exhilarating sensation known to only a few lucky scientists. Absence of graft triggers the opposite sen- sation of complete disappointment, which has led several teams to focus their attention on this particular problem with the xenograft approach. In this issue of Haematologica, Krevvata et al. put forward fundamental new insights to
help improve xenograft of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).2
Myelodysplastic syndrome and acute myeloid leukemia are myeloid neoplasms that disrupt normal hematopoiesis. This group of myeloid leukemias could be considered as a continuum consisting of a multitude of different leukemias, including all possible myeloid abnor- malities. This results in a wide range of severity and patient overall survival (OS). MDS patients have globally better OS than AML patients, and some MDS evolve inevitably towards AML. Interestingly, the first attempts at AML/MDS xenograft quickly revealed, through the repartition of samples engrafting and non-engrafting the mice, that the engraftment potential was perfectly linked with the aggressiveness of the leukemia, since AML sam- ples are usually more easy to engraft than MDSs.3,4 Many independent studies have offered different reasons for engraftment failure, but none can satisfactorily explain it. Possible explanations are either related to the host immune environment or to the defect of the grafted cells or to the graft and host compatibility.
The innate and adaptive immune response of the host environment is an obvious and very clear obstacle for the
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