Granulocyte-Macrophage Progenitors as Candidate Leukemic Stem Cells in Blast-Crisis CML

作者: Catriona H.M. Jamieson , Laurie E. Ailles , Scott J. Dylla , Manja Muijtjens , Carol Jones

DOI: 10.1056/NEJMOA040258

关键词: Stem cellCateninCancer researchImmunologyImatinib mesylateBiologyHaematopoiesisLymphoid enhancer-binding factor 1LeukemiaProgenitor cellMyeloid

摘要: methods We used fluorescence-activated cell sorting to isolate hematopoietic stem cells, common myeloid progenitors, granulocyte–macrophage and megakaryocyte–erythroid progenitors from marrow during several phases of CML normal marrow. BCR-ABL, b -catenin , LEF-1 transcripts were compared by means a quantitative reverse-transcriptase–polymerase-chain-reaction assay in cells progenitors. Confocal fluorescence microscopy lymphoid enhancer factor/T-cell factor reporter detect nuclear these cells. In vitro replating assays identify self-renewing as candidate leukemic the dependence self-renewal on activation was tested lentiviral transduction with axin, an inhibitor pathway. results The progenitor pool patients blast crisis imatinib-resistant expanded, expressed had elevated levels Unlike formed self-renewing, replatable colonies, capacity reduced enforced expression axin. conclusions Activation appears enhance activity potential

参考文章(58)
Karl Willert, Jeffrey D. Brown, Esther Danenberg, Andrew W. Duncan, Irving L. Weissman, Tannishtha Reya, John R. Yates, Roel Nusse, Wnt proteins are lipid-modified and can act as stem cell growth factors Nature. ,vol. 423, pp. 448- 452 ,(2003) , 10.1038/NATURE01611
C. M. Baum, I. L. Weissman, A. S. Tsukamoto, A. M. Buckle, B. Peault, Isolation of a candidate human hematopoietic stem-cell population Proceedings of the National Academy of Sciences of the United States of America. ,vol. 89, pp. 2804- 2808 ,(1992) , 10.1073/PNAS.89.7.2804
Jos Domen, Irving L. Weissman, Hematopoietic stem cells need two signals to prevent apoptosis; BCL-2 can provide one of these, Kitl/c-Kit signaling the other. Journal of Experimental Medicine. ,vol. 192, pp. 1707- 1718 ,(2000) , 10.1084/JEM.192.12.1707
C Sirard, T Lapidot, J Vormoor, JD Cashman, M Doedens, B Murdoch, N Jamal, H Messner, L Addey, M Minden, P Laraya, A Keating, A Eaves, PM Lansdorp, CJ Eaves, JE Dick, Normal and leukemic SCID-repopulating cells (SRC) coexist in the bone marrow and peripheral blood from CML patients in chronic phase, whereas leukemic SRC are detected in blast crisis. Blood. ,vol. 87, pp. 1539- 1548 ,(1996) , 10.1182/BLOOD.V87.4.1539.BLOODJOURNAL8741539
Hanna K. A. Mikkola, Jenny Klintman, Haidi Yang, Hanno Hock, Thorsten M. Schlaeger, Yuko Fujiwara, Stuart H. Orkin, Haematopoietic stem cells retain long-term repopulating activity and multipotency in the absence of stem-cell leukaemia SCL/ tal-1 gene Nature. ,vol. 421, pp. 547- 551 ,(2003) , 10.1038/NATURE01345
Roel Nusse, Albert van Ooyen, David Cox, Yuen Kai T. Fung, Harold Varmus, Mode of proviral activation of a putative mammary oncogene ( int -1) on mouse chromosome 15 Nature. ,vol. 307, pp. 131- 136 ,(1984) , 10.1038/307131A0
Erming Tian, Fenghuang Zhan, Ronald Walker, Erik Rasmussen, Yupo Ma, Bart Barlogie, John D. Shaughnessy, The Role of the Wnt-Signaling Antagonist DKK1 in the Development of Osteolytic Lesions in Multiple Myeloma New England Journal of Medicine. ,vol. 349, pp. 2483- 2494 ,(2003) , 10.1056/NEJMOA030847
T. Lugo, A. Pendergast, A. Muller, O. Witte, Tyrosine kinase activity and transformation potency of bcr-abl oncogene products. Science. ,vol. 247, pp. 1079- 1082 ,(1990) , 10.1126/SCIENCE.2408149