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

• Published in: Haematologica (Roma) 2011-01, Vol.96 (1), p.102-109
• Main Authors: MARTIN-ANTONIO, Beatriz, CARMONA, Magdalena, FALANTES, Jose, GIL, Encarnación, BAEZ, Alicia, SUAREZ, Maria, MARIN, Pedro, ESPIGADO, Ildefonso, URBANO-ISPIZUA, Alvaro
• Format: Article
• Language: English
• Subjects: Antigens, CD34 - genetics; Biological and medical sciences; Cells, Cultured; Chemokine CXCL12 - genetics; Granulocyte Colony-Stimulating Factor - administration & dosage; Hematologic and hematopoietic diseases; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cells - drug effects; Humans; Hyaluronan Receptors - genetics; Medical sciences; Original; Polymorphism, Single Nucleotide - genetics; Receptors, Colony-Stimulating Factor - genetics; Recombinant Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Tissue Donors; Vascular Cell Adhesion Molecule-1 - genetics
• ISSN: 0390-6078; 1592-8721
• DOI: 10.3324/haematol.2010.026401

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