生物谷報(bào)道：4月27日的《科學(xué)》雜志報(bào)道,，一個(gè)新的小鼠模型幫助癌癥研究人員識(shí)別能在小鼠身上模仿白血病的人細(xì)胞類型,、并隨著疾病的進(jìn)展監(jiān)測這些細(xì)胞。這項(xiàng)研究也許能帶來根絕白血病啟動(dòng)細(xì)胞的更有效的白血病治療方法,。
小鼠模型在研究白血病上至關(guān)重要,，但是因?yàn)榘籽〖?xì)胞來自小鼠，這些模型的作用有限,。Frédéric Barabé和同事報(bào)告的這個(gè)新模型中,，原生人血細(xì)胞表達(dá)一個(gè)白血病融合基因的混合系、分化、在小鼠身上扎根,、最終導(dǎo)致與骨髓或淋巴有關(guān)的急性白血病,。因?yàn)檫@些小鼠身上的癌癥細(xì)胞具有人類疾病的特征，它們也許能為啟動(dòng)白血病和導(dǎo)致其發(fā)展的過程提供新的線索,。
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)].
原文出處：
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......
作者簡介：
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, University of Toronto
Princess Margaret Hospital
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.
