Defective homing is associated with altered Cdc42 activity in cells from patients with Fanconi anemia group A

Xiaoling Zhang, Xun Shang, Fukun Guo, Kim Murphy, Michelle Kirby, Patrick Kelly, Lilith Reeves, Franklin O. Smith, David A. Williams, Yi Zheng, Qishen Pang

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

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 into mouse models. Using cells from patients carrying mutations in FA complementation group A (FA-A), we show that when transplanted into nonobese diabetic/severe combined immunodeficiency (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 reexpression 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.

Original languageEnglish (US)
Pages (from-to)1683-1686
Number of pages4
JournalBlood
Volume112
Issue number5
DOIs
StatePublished - Sep 1 2008
Externally publishedYes

Fingerprint

Fanconi Anemia
Bone
Adhesion
Defects
Fanconi Anemia Complementation Group Proteins
rho GTP-Binding Proteins
Monomeric GTP-Binding Proteins
Stem cells
Cells
Bone Marrow
Cell-Matrix Junctions
Severe Combined Immunodeficiency
Bone Marrow Transplantation
Bone Marrow Cells
Stem Cells
Mutation

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Zhang, X., Shang, X., Guo, F., Murphy, K., Kirby, M., Kelly, P., ... Pang, Q. (2008). Defective homing is associated with altered Cdc42 activity in cells from patients with Fanconi anemia group A. Blood, 112(5), 1683-1686. https://doi.org/10.1182/blood-2008-03-147090

Defective homing is associated with altered Cdc42 activity in cells from patients with Fanconi anemia group A. / Zhang, Xiaoling; Shang, Xun; Guo, Fukun; Murphy, Kim; Kirby, Michelle; Kelly, Patrick; Reeves, Lilith; Smith, Franklin O.; Williams, David A.; Zheng, Yi; Pang, Qishen.

In: Blood, Vol. 112, No. 5, 01.09.2008, p. 1683-1686.

Research output: Contribution to journalArticle

Zhang, X, Shang, X, Guo, F, Murphy, K, Kirby, M, Kelly, P, Reeves, L, Smith, FO, Williams, DA, Zheng, Y & Pang, Q 2008, 'Defective homing is associated with altered Cdc42 activity in cells from patients with Fanconi anemia group A', Blood, vol. 112, no. 5, pp. 1683-1686. https://doi.org/10.1182/blood-2008-03-147090
Zhang, Xiaoling ; Shang, Xun ; Guo, Fukun ; Murphy, Kim ; Kirby, Michelle ; Kelly, Patrick ; Reeves, Lilith ; Smith, Franklin O. ; Williams, David A. ; Zheng, Yi ; Pang, Qishen. / Defective homing is associated with altered Cdc42 activity in cells from patients with Fanconi anemia group A. In: Blood. 2008 ; Vol. 112, No. 5. pp. 1683-1686.
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