Kelliher M A, McLaughlin J, Witte O N, Rosenberg N
Department of Pathology, Tufts University School of Medicine, Boston, MA 02111.
Proc Natl Acad Sci U S A. 1990 Sep;87(17):6649-53. doi: 10.1073/pnas.87.17.6649.
The v-abl gene in Abelson virus induces pre-B-cell lymphoma in mice while the BCR/ABL oncogene is associated with chronic myelogenous leukemia and some cases of acute lymphocytic leukemia in humans. Understanding the mechanisms by which these oncogenes affect various cell types has been hampered by a paucity of experimental systems that reproduce the range of biological effects associated with them. We have developed an experimental system in which murine hematopoietic stem cell populations are infected with either v-abl or BCR/ABL retroviruses and are used to reconstitute lethally irradiated mice. Irrespective of the form of activated abl, greater than 90% of the animals reconstituted with such cells develop tumors. About 50% of them develop a myeloproliferative syndrome that shares several features with the chronic phase of chronic myelogenous leukemia; the remaining animals succumb to pre-B-cell lymphomas. The myeloproliferative syndrome is characterized by large numbers of clonally derived, infected myeloid cells. This model will allow study of the mechanism by which activated abl genes affect hematopoietic precursors in chronic myelogenous leukemia. Furthermore, our results demonstrate that introduction of an activated abl gene into the appropriate target cell, not the structure of the gene, is the major determinant in myeloid cell specificity.
阿贝尔森病毒中的v-abl基因可在小鼠中诱发前B细胞淋巴瘤，而BCR/ABL癌基因与人类慢性粒细胞白血病及某些急性淋巴细胞白血病病例相关。由于缺乏能够重现与这些癌基因相关的一系列生物学效应的实验系统，了解这些癌基因影响各种细胞类型的机制受到了阻碍。我们开发了一种实验系统，其中用v-abl或BCR/ABL逆转录病毒感染小鼠造血干细胞群体，并用于重建经致死性照射的小鼠。无论激活的abl形式如何，用此类细胞重建的动物中超过90%会发生肿瘤。其中约50%会发展出一种骨髓增殖综合征，该综合征与慢性粒细胞白血病的慢性期有若干共同特征；其余动物死于前B细胞淋巴瘤。骨髓增殖综合征的特征是大量克隆衍生的受感染髓样细胞。该模型将有助于研究激活的abl基因在慢性粒细胞白血病中影响造血前体的机制。此外，我们的结果表明，将激活的abl基因导入适当的靶细胞，而非基因的结构，是髓样细胞特异性的主要决定因素。
