Long-Term Malignant Hematopoiesis in Human Acute Leukemia Bone Marrow Biopsies Implanted in Severe Combined Immunodeficiency Mice
Faezeh Legrand,
Ibrahim Khazaal,
Michel Peuchmaur,
Odile Fenneteau,
Hélène Cavé,
Pierre Rohrlich,
Etienne Vilmer, and
Bruno Péault
From the Institut d'Embryologie Cellulaire et Moléculaire, Centre National de la Recherche Scientifique Unité Propre de Recherche (CNRS UPR) UPR 9064, Nogent-sur-Marne; and Hôpital Robert Debré, Paris, France.
Bone marrow (BM) trephine biopsies from 15 pediatric patients with acute lymphoid (ALL) or myeloid (AML) leukemia were engrafted subcutaneously into severe combined immunodeficiency (SCID) mice conditioned by 200 cGy total-body irradiation. Implants were harvested 5 to 19 weeks later for histologic, cytologic, and/or flow cytometric analysis of the residing marrow. Eighteen of 19 grafts contained viable human leukemic cells to various extents as assessed by one or more of these methods. Thirteen of 14 implants analyzed by flow cytometry included high numbers of tumor cells, accounting for 85% to 100% of the total nucleated cells in seven of them. Histologically, engrafted marrow samples exhibited areas of blastic infiltration, and tumor-specific gene rearrangements were retrieved in long-term engrafted biopsies. Importantly, engrafted mice remained perfectly healthy even 5 months posttransplantation, and no human tumor cell dissemination was detected in the hematolymphoid and nonhematopoietic tissues at the time of autopsy. These results demonstrate that human malignant hematopoiesis can be sustained long-term in its original, intact marrow stromal environment transplanted in appropriately conditioned immunodeficient mice.
Blood, Vol. 90 No. 5 (September 1), 1997:
pp. 2001-2009
© 1997 by The American Society of Hematology.
