Author Affiliations

  1. Beatriz Martín-Antonio1,*,
  2. Magdalena Carmona1,
  3. Jose Falantes1,
  4. Encarnación Gil1,
  5. Alicia Baez1,
  6. María Suarez2,
  7. Pedro Marín2,
  8. Ildefonso Espigado1 and
  9. Álvaro Urbano-Ispizua1,*
  1. 1 Hospital Universitario Virgen del Rocío, Hematology Department, Universidad de Sevilla, Instituto de Biomedicina de Sevilla (IBIS), Seville, Spain
  2. 2 Hospital Universitario Clinic, Hematology Department, Universidad de Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
  1. Correspondence: Beatriz Martín Antonio, Department of Hematology, Hospital Clinic University of Barcelona, Calle Casanova 143. 08034 Barcelona (Spain). E-mail: bmartina{at}clinic.ub.es
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Abstract

Background The number of CD34+ cells mobilized from bone marrow to peripheral blood after administration of granulocyte colony-stimulating factor varies greatly among healthy donors. This fact might be explained, at least in part, by constitutional differences in genes involved in the interactions tethering CD34+ cells to the bone marrow.

Design and Methods We analyzed genetic characteristics associated with CD34+ cell mobilization in 112 healthy individuals receiving granulocyte colony-stimulating factor (filgrastim; 10 μg/kg; 5 days).

Results Genetic variants in VCAM1 and in CD44 were associated with the number of CD34+ cells in peripheral blood after granulocyte colony-stimulating factor administration (P=0.02 and P=0.04, respectively), with the quantity of CD34+ cells ×106/kg of donor (4.6 versus 6.3; P<0.001 and 7 versus 5.6; P=0.025, respectively), and with total CD34+ cells ×106 (355 versus 495; P=0.002 and 522 versus 422; P=0.012, respectively) in the first apheresis. Of note, granulocyte colony-stimulating factor administration was associated with complete disappearance of VCAM1 mRNA expression in peripheral blood. Moreover, genetic variants in granulocyte colony-stimulating factor receptor (CSF3R) and in CXCL12 were associated with a lower and higher number of granulocyte colony-stimulating factor-mobilized CD34+ cells/μL in peripheral blood (81 versus 106; P=0.002 and 165 versus 98; P=0.02, respectively) and a genetic variant in CXCR4 was associated with a lower quantity of CD34+ cells ×106/kg of donor and total CD34+ cells ×106 (5.3 versus 6.7; P=0.02 and 399 versus 533; P=0.01, respectively).

Conclusions In conclusion, genetic variability in molecules involved in migration and homing of CD34+ cells influences the degree of mobilization of these cells.

  • Received April 16, 2010.
  • Revision received September 9, 2010.
  • Accepted September 13, 2010.
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