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Modeling the Initiation and Progression of Human Acute Leukemia in Mice
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Modeling the Initiation and Progression of Human Acute Leukemia in Mice
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Journal Article
Modeling the Initiation and Progression of Human Acute Leukemia in Mice
2007
Overview
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.
Publisher
American Association for the Advancement of Science,The American Association for the Advancement of Science
Subject
/ Biological and medical sciences
/ Blood
/ Cell Transformation, Neoplastic
/ Cells
/ Gene Rearrangement, B-Lymphocyte, Heavy Chain
/ genes
/ Hematologic and hematopoietic diseases
/ Hematopoietic Stem Cell Transplantation
/ Hematopoietic Stem Cells - metabolism
/ Humans
/ Immunoglobulin Heavy Chains - genetics
/ Leukemia
/ Leukemia, Lymphoid - pathology
/ Leukemia, Lymphoid - physiopathology
/ Leukemia, Myeloid - pathology
/ Leukemia, Myeloid - physiopathology
/ Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
/ Mice
/ Myeloid-Lymphoid Leukemia Protein - genetics
/ Oncogene Proteins, Fusion - genetics
/ Rodents
