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


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.
Martín-Antonio
Beatriz
B
Department of Hematology, Hospital Clinic University of Barcelona, Barcelona, Spain. bmartina@clinic.ub.es
Carmona
Magdalena
M
Falantes
Jose
J
Gil
Encarnación
E
Baez
Alicia
A
Suarez
María
M
Marín
Pedro
P
Espigado
Ildefonso
I
Urbano-Ispizua
Alvaro
A
D018952:Antigens, CD34 / Q000235:genetics*; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000235:genetics; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D016184:Receptors, Colony-Stimulating Factor / Q000235:genetics; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014019:Tissue Donors; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics*
D018952:Antigens, CD34; C497483:CD44 protein, human; C517047:CSF3R protein, human; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D018960:Hyaluronan Receptors; D012333:RNA, Messenger; D016184:Receptors, Colony-Stimulating Factor; D011994:Recombinant Proteins; D019010:Vascular Cell Adhesion Molecule-1; D016179:Granulocyte Colony-Stimulating Factor