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Haematologica. 2011 Jan;96(1):102-9. doi: 10.3324/haematol.2010.026401. Epub 2010 Sep 17.

Impact of constitutional polymorphisms in VCAM1 and CD44 on CD34+ cell collection yield after administration of granulocyte colony-stimulating factor to healthy donors.

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1
Department of Hematology, Hospital Clinic University of Barcelona, Barcelona, Spain. bmartina@clinic.ub.es

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.

PMID:
20851866
PMCID:
PMC3012773
DOI:
10.3324/haematol.2010.026401
[Indexed for MEDLINE]
Free PMC Article
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