MLL-ENL causes a reversible and myc-dependent block of myelomonocytic cell differentiation.

作者: Robert Karl Slany , Marco Birke , María-Paz García-Cuéllar , Silke Schreiner , Johann Greil

DOI:

关键词:

摘要: The translocation t(11;19) is a recurrent feature of subgroup acute leukemiasoccurring in infants. This event fuses the genes MLL and ENL creates leukemogenic oncoprotein MLL-ENL. We studied effect retroviral MLL-ENL expression primary mouse hematopoietic cells show here that requires Myc to establish reversible differentiation arrest myelomonocytic precursor population. MLL-ENL-transduced proliferated as immature myeloid presence interleukin 3. addition granulocyte colony-stimulating factor reversed maturation block set by induced development mature granulocytes macrophages accompanied growth arrest. Gene analysis indicated down-regulation proto-oncogene c-myc several target during factor-mediated differentiation. role transformation pathway was tested modulating effective protein concentrations transduced cells. Cotransduction dominant-negative neutralized precluded transformation. In contrast, constitutive cooperated with caused cell population an irreversible

参考文章(37)
Hideshi Yagi, Kenji Deguchi, Atsufumi Aono, Yoshihiko Tani, Tadamitsu Kishimoto, Toshihisa Komori, Growth Disturbance in Fetal Liver Hematopoiesis of Mll-Mutant Mice Blood. ,vol. 92, pp. 108- 117 ,(1998) , 10.1182/BLOOD.V92.1.108.413K11_108_117
RG Hawley, FH Lieu, AZ Fong, Teresa S Hawley, None, Versatile retroviral vectors for potential use in gene therapy. Gene Therapy. ,vol. 1, pp. 136- 138 ,(1994)
Jay L. Hess, Benjamin D. Yu, Bin Li, Rob Hanson, Stanley J. Korsmeyer, Defects in yolk sac hematopoiesis in Mll-null embryos Blood. ,vol. 90, pp. 1799- 1806 ,(1997) , 10.1182/BLOOD.V90.5.1799
Nidal Mahgoub, Robert I. Parker, Matthew R. Hosler, Pamelyn Close, Naomi J. Winick, Margaret Masterson, Kevin M. Shannon, Carolyn A. Felix, RAS mutations in pediatric leukemias withMLL gene rearrangements Genes, Chromosomes and Cancer. ,vol. 21, pp. 270- 275 ,(1998) , 10.1002/(SICI)1098-2264(199803)21:3<270::AID-GCC14>3.0.CO;2-T
Alan Forster, Teresa A Larson, Sarah Bell, Andrew N.J McKenzie, Gareth King, Terence H Rabbitts, Javier Corral, Isabelle Lavenir, Helen Impey, Alan J Warren, An Mll–AF9 Fusion Gene Made by Homologous Recombination Causes Acute Leukemia in Chimeric Mice: A Method to Create Fusion Oncogenes Cell. ,vol. 85, pp. 853- 861 ,(1996) , 10.1016/S0092-8674(00)81269-6
Maarten van Lohuizen, Sjef Verbeek, Blanca Scheljen, Ellen Wientjens, Hanneke van der Guidon, Anton Berns, Identification of cooperating oncogenes in Eμ-myc transgenic mice by provirus tagging Cell. ,vol. 65, pp. 737- 752 ,(1991) , 10.1016/0092-8674(91)90382-9
Y. Gu, T. Nakamura, H. Alder, R. Prasad, O. Canaani, G. Cimino, C.M. Croce, E. Canaani, The t(4;11) chromosome translocation of human acute leukemias fuses the ALL-1 gene, related to Drosophila trithorax, to the AF-4 gene Cell. ,vol. 71, pp. 701- 708 ,(1992) , 10.1016/0092-8674(92)90603-A
R. Prasad, T. Yano, C. Sorio, T. Nakamura, R. Rallapalli, Y. Gu, D. Leshkowitz, C. M. Croce, E. Canaani, Domains with transcriptional regulatory activity within the ALL1 and AF4 proteins involved in acute leukemia Proceedings of the National Academy of Sciences of the United States of America. ,vol. 92, pp. 12160- 12164 ,(1995) , 10.1073/PNAS.92.26.12160
L. Sun, N. Heerema, L. Crotty, X. Wu, C. Navara, A. Vassilev, M. Sensel, G. H. Reaman, F. M. Uckun, Expression of dominant-negative and mutant isoforms of the antileukemic transcription factor Ikaros in infant acute lymphoblastic leukemia Proceedings of the National Academy of Sciences of the United States of America. ,vol. 96, pp. 680- 685 ,(1999) , 10.1073/PNAS.96.2.680