Impact of constitutional polymorphisms in VCAM1 and CD44 on CD34+ cell collection yield after administration of granulocyte colony-stimulating factor to healthy donors.
Haematologica
; 96(1): 102-9, 2011 Jan.
Article
in En
| MEDLINE
| ID: mdl-20851866
ABSTRACT
UNLABELLED 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Granulocyte Colony-Stimulating Factor
/
Vascular Cell Adhesion Molecule-1
/
Hyaluronan Receptors
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Antigens, CD34
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Hematopoietic Stem Cell Mobilization
/
Polymorphism, Single Nucleotide
Limits:
Humans
Language:
En
Journal:
Haematologica
Year:
2011
Document type:
Article
Affiliation country:
Spain
Publication country:
IT
/
ITALIA
/
ITALY
/
ITÁLIA