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Blood, 1 September 2008, Vol. 112, No. 5, pp. 1683-1686. Prepublished online as a Blood First Edition Paper on June 18, 2008; DOI 10.1182/blood-2008-03-147090. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-03-147090v1 112/5/1683    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Zhang, X. Articles by Pang, Q. Search for Related Content PubMed PubMed Citation Articles by Zhang, X. Articles by Pang, Q. Related Collections Related Articles in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 21, 2008 Accepted June 2, 2008 Defective homing is associated with altered Cdc42 activity in cells from Fanconi anemia group A patients Xiaoling Zhang, Xun Shang, Fukun Guo, Kim Murphy, Michelle Kirby, Patrick Kelly, Lilith Reeves, Franklin O Smith, David A Williams, Yi Zheng, and Qishen Pang* Experimental Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States Hematology Clinical Research & Development, Wyeth Research, Cambridge, MA, United States Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States Division of Hematology/Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States Division of Hematology/Oncology, Children's Hospital Boston, Boston, MA, United States * Corresponding author; email: qishen.pang{at}cchmc.org. Previous studies showed that Fanconi anemia (FA) murine stem cells have defective reconstitution after bone marrow (BM) transplantation. The mechanism underlying this defect is not known. Here we report defective homing of FA patient BM progenitors transplanted in mouse models. Using cells from patients carrying mutations in FA complementation group A (FA-A), we show that when transplanted into NOD/SCID recipient mice, FA-A BM cells exhibited impaired homing activity. FA-A cells also showed defects in both cell-cell and cell-matrix adhesion. Complementation of FA-A deficiency by re-expression of FANCA readily restored adhesion of FA-A cells. A significant decrease in the activity of the Rho GTPase Cdc42 was found associated with these defective functions in patient-derived cells, and expression of a constitutively active Cdc42 mutant was able to rescue the adhesion defect of FA-A cells. These results provide the first evidence that FA proteins influence human BM progenitor homing and adhesion via the small GTPase Cdc42-regulated signaling pathway. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Articles in Blood Online: Is hematopoietic stem cell homing deficient in Fanconi anemia? Lee O'Neill, Amy M. Skinner, and Peter Kurre Blood 2009 113: 5361. [Full Text] [PDF] Response: Homing defect in hematopoietic cells from Fanconi anemia patients Xiaoling Zhang and Qishen Pang Blood 2009 113: 5362. [Full Text] [PDF] This article has been cited by other articles: L. O'Neill, A. M. Skinner, and P. Kurre Is hematopoietic stem cell homing deficient in Fanconi anemia? Blood, May 21, 2009; 113(21): 5361 - 5361. [Full Text] [PDF] X. Zhang and Q. Pang Response: Homing defect in hematopoietic cells from Fanconi anemia patients Blood, May 21, 2009; 113(21): 5362 - 5362. [Full Text] [PDF]

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