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

Abstract

The online version of this article has a Supplementary Appendix. BackgroundThe 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 MethodsWe analyzed genetic characteristics associated with CD34 + cell mobilization in 112 healthy individuals receiving granulocyte colony-stimulating factor (filgrastim; 10 μg/kg; 5 days). ResultsGenetic 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 ¥10 6 /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 ¥10 6 (355 versus 495; P=0.002 and 522 versus 422; P=0.012, respectively) in the first apheresis. Of note, granulocyte colonystimulating 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 ¥10 6 /kg of donor and total CD34 + cells ¥10 6 (5.3 versus 6.7; P=0.02 and 399 versus 533; P=0.01, respectively). ConclusionsIn conclusion, genetic variability in molecules involved in migration and homing of CD34 + cells influences the degree of mobilization of these cells.

G-CSF in Healthy Allogeneic Stem Cell Donors

“…This result could be confirmed by Bogunia-Kubik et al [39] and Ben et al [40]. Martin-Antonio et al [41] reported the same finding and observed associations between mobilization ability and even more polymorphisms, including VCAM-1 und CD44. An analysis of our group could not show a significant association of the CXCL12-3′A allele with more efficient stem cell mobilization in 463 unrelated donors (Schmidt J, Bornhäuser M et al, submitted).…”

Transmissible cytotoxicity of multiple myeloma cells by cord blood-derived NK cells is mediated by vesicle trafficking

“…However, we still observed vesicle transfer from CB-NK to MM cells and also secondary transfer between MM cells (Figure 7b). Because CXCL12 tethers hemopoietic cells into the stroma, 28 we measured CXCL12 secretion by the stroma and observed a reduced CXCL12 secretion after the addition of MM cells or MM cells and CB-NK (Figure 7c, Po0.05), suggesting a possible role for CXCL12 in reducing the anti-MM cytotoxicity of CB-NK. Therefore we performed cytotoxicity assay adding AMD3100, which inhibits binding of CXCL12 to CXCR4 in hemopoietic cells.…”

A constitutional variant in the transcription factor EP300 strongly influences the clinical outcome of patients submitted to allo-SCT

“…RNA isolation was performed as previously described. 18 Real-time RT-PCR analysis for all the genes but P53 was carried out using the 7900HT Fast Real-Time PCR System (Applied Biosystems). For P53, real time RT-PCR reactions were done in a 25-mL volume containing complementary DNA generated from 10 ng of original RNA template, 300 nM each of specific forward and reverse primers (p53Fw: 5 0 -GCCCACTTCACCGTACTAACC-3 0 and p53Rv: 5 0 -GCCCAA CTGTAGAAACTACCA-3 0 ) and 12.5 mL of iQ-SYBR Green Supermix (Bio-Rad, Hercules, CA, USA).…”