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Modeling the Initiation and Progression of Human Acute Leukemia in Mice
Ist Teil von
Science (American Association for the Advancement of Science), 2007-04, Vol.316 (5824), p.600-604
Ort / Verlag
Washington, DC: American Association for the Advancement of Science
Erscheinungsjahr
2007
Link zum Volltext
Quelle
Science magazine suite
Beschreibungen/Notizen
Our understanding of leukemia development and progression has been hampered by the lack of in vivo models in which disease is initiated from primary human hematopoietic cells. We showed that upon transplantation into immunodeficient mice, primitive human hematopoietic cells expressing a mixed-lineage leukemia (MLL) fusion gene generated myeloid or lymphoid acute leukemias, with features that recapitulated human diseases. Analysis of serially transplanted mice revealed that the disease is sustained by leukemia-initiating cells (L-ICs) that have evolved over time from a primitive cell type with a germline immunoglobulin heavy chain (IgH) gene configuration to a cell type containing rearranged IgH genes. The L-ICs retained both myeloid and lymphoid lineage potential and remained responsive to microenvironmental cues. The properties of these cells provide a biological basis for several clinical hallmarks of MLL leukemias.