Science：一种新的研究白血病的老鼠模型被建立
生物谷报道：
小鼠模型在研究白血病上至关重要，但是因为白血病细胞来自小鼠，这些模型的作用有限。Frédéric Barabé和同事报告的这个新模型中，原生人血细胞表达一个白血病融合基因的混合系、分化、在小鼠身上扎根、最终导致与骨髓或淋巴有关的急性白血病。因为这些小鼠身上的癌症细胞具有人类疾病的特征，它们也许能为启动白血病和导致其发展的过程提供新的线索。
Fig. 1. Morphology, tissue infiltration, and immunophenotype of MLL-induced ALL and AML. (A) Kaplan-Meier survival analysis of control and MLL-ENL mice. n, number of mice. (B) Blood smears and BM cytospins [May-Grünwald-Giemsa (MGG) staining] of representative mice injected with control cells, MLL-ENL transduced cells, and MLL-AF9 transduced cells. Scale bars, 10 µm. (C) Organ infiltration by lymphoblasts in a representative MLL-ENL mouse. Tissue sections are stained with hematoxylin and eosin (H&E) and with a human-specific antibody to CD45. Scale bars, 100 µm (lung, kidney, and testis) or 25 µm (brain). (D and E) Flow cytometric analysis of BM and blood from representative mice with MLL-induced B-ALL. The upper row in (D) shows the human erythroid cells (GlyA+ cells) and the human leukocytes (CD45+GlyA– cells) that compose the human graft; the cells of mouse origin are in the lower left quadrant (CD45–GlyA– cells). Contour plots are gated on all live cells [upper row in (D)] or on human CD45+ cells [(D), lower row, and (E)].
原文出处：
Modeling the Initiation and Progression of Human Acute Leukemia in Mice
Frédéric Barabé, James A. Kennedy, Kristin J. Hope, and John E. Dick
Science 27 April 2007 316: 600-604 [DOI: 10.1126/science.1139851] (in Reports)
......Kennedy 1 5 * Kristin J. Hope 1 5 John E. Dick 1 5 To whom correspondence should...and the Terry Fox Foundation (to J.E.D.). Supporting Online Material...James A. Kennedy, Kristin J. Hope, John E. Dick Supporting Online Material This......
作者简介：
John E. Dick, Ph.D.
Canada Research Chair in Stem Cell Biology
Director, Program in Stem Cell Biology,
Toronto General Research Institute, University Health Network
Dept of Molecular and Medical Genetics,
Princess Margaret
Hematopoietic development:
The long term objectives of my research program are: to understand the organization and developmental program of human hematopoietic stem cells; and to characterize how expression of key regulatory genes leads to leukemic transformation. We have developed novel in vivo assays for normal human hematopoietic stem cells by transplantation of normal human bone marrow into immune deficient mice. In addition to normal cells, we have established an animal model of human leukemia that is analogous to the progression of the disease in humans. These advances lay the foundation for a novel approach to create animal models of many human diseases providing a unique alternative to transgenic mice. We have also developed a system to genetically manipulate the human hematopoietic cells with retrovirus vectors expressing human growth regulatory genes and oncogenes. This will enable us to mark stem cells to follow their lineage development as well as to express a variety of growth regulatory genes to determine their role in the stem cell developmental program.
Publications:
Güenechea G*, Gan OI*, Dorrell C*, Dick, JE (2001) Distinct classes of human stem cells that differ in proliferative and self-renewal potential. Nature Immunology 2: 75-82 *first three authors made equal contribution to the work.
Pereira DS, Dorrell CS, Ito CY, Gan OI, Murdoch B, Rao VN, Zou JP, Reddy ESP, Dick JE (1998) Retroviral transduction of TLS-ERG initiates a leukemogenic program in normal human hematopietic cells. Proc. Natl. Acad.Sci. USA 95: 8239-8244.
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