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Blood, 1 February 2006, Vol. 107, No. 3, pp. 1166-1173.
Prepublished online as a Blood First Edition Paper on October 18, 2005; DOI 10.1182/blood-2005-06-2325.
Previous Article | Next Article 
Submitted June 10, 2005
Accepted September 27, 2005
AML engraftment in the NOD/SCID assay reflects the outcome of AML: implications for our understanding of the heterogeneity of AML
Daniel J Pearce, David Taussig, Kazem Zibara, Lan-Lan Smith, Christopher M Ridler, Claude Preudhomme, Bryan D Young, Ama Z Rohatiner, T A Lister, and Dominique Bonnet*
Hematopoietic Stem Cell Laboratory, London Research Institute, Cancer Research UK, London, United Kingdom
Hematopoietic Stem Cell Laboratory, London Research Institute, Cancer Research UK, London, United Kingdom; Cancer Research UK Medical Oncology Unit, St. Bartholomew's Hospital, London, United Kingdom
Hematopoietic Stem Cell Laboratory, London Research Institute, Cancer Research UK, London, United Kingdom; Medical Oncology Laboratory, Cancer Research UK, Queen Mary & St Bartholomew's Medical School, London, United Kingdom
Laboratoire d'hematologie A, Hopital Calmette, Lille, France
Medical Oncology Laboratory, Cancer Research UK, Queen Mary & St Bartholomew's Medical School, London, United Kingdom
Cancer Research UK Medical Oncology Unit, St. Bartholomew's Hospital, London, United Kingdom
* Corresponding author; email: dominique.bonnet{at}cacner.org.uk.
The non-obese diabetic/severe combined immunodeficient (NOD/SCID) assay is the current model for assessment of human normal and leukemic stem cells. We explored why 51% of 59 acute myeloid leukemia (AML) patients were unable to initiate leukemia in NOD/SCID mice. Increasing the cell dose, using more permissive recipients and alternative tissue sources, did not cause AML engraftment in most previously non-engrafting AML samples. Homing of AML cells to the marrow was the same between engrafters and non-engrafters. FLT-3 ITD and nucleophosmin mutations occurred at a similar frequency in engrafters and non-engrafters. The only variable that was related to engraftment ability was the karyotypically-defined risk stratification of individual AML cases. Interestingly, follow-up of younger patients with intermediate-risk AML revealed a significant difference in overall survival between NOD/SCID-engrafting and non-engrafting AMLs. Hence, the ability of AML to engraft in the NOD/SCID assay seems to be an inherent property of AML cells, independent of homing, conditioning or cell frequency/source, which is directly related to prognosis. Our results suggest an important difference between leukemic initiating cells between engrafting and non-engrafting AML cases that correlates with treatment response.

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