CXCL12 polymorphism and malignant cell dissemination/tissue infiltration in acute myeloid leukemia.
Stromal cell-derived factor 1 (SDF-1), a chemokine abundantly produced by the bone marrow microenvironment, and its receptor CXCR4 have crucial roles in malignant cell trafficking. In acute myeloid leukemia (AML), blasts invade the bloodstream and may localize in extramedullar sites, with variations from one patient to another. We hypothesized that a polymorphism in the SDF-1 coding gene (CXCL12 G801A) could influence blast dissemination and tissue infiltration in AML. CXCL12 G801A polymorphism was determined in 86 adult patients and 100 healthy volunteers. The allelic status and CXCR4 expression on bone marrow blasts were analyzed in relation to peripheral blood blast (PBB) counts and frequency of extramedullar tumor sites. 801A carrier status (801G/A, 801A/A) was found to be associated with a higher PBB count compared with 801G/G homozygous patients (P=0.031) and higher frequency of extramedullar tumor sites (odds ratio 2.92, 95% confidence interval 1.18-7.21, P=0.018). Moreover, the PBB count was correlated with CXCR4 expression (correlation coefficient 0.546, P=0.001) when considering 801A carriers. In conclusion, a polymorphism in the SDF-1 gene is shown for the first time to be associated with the clinical presentation of a malignant hematological disease and more generally with the risk of distant tissue infiltration by tumor cells.
Dommange
Florence
F
CHRU de Tours, Laboratoire d'Hématologie, Service d;Hématologie et Thérapie Cellulaire.
Cartron
Guillaume
G
Espanel
Claire
C
Gallay
Nathalie
N
Domenech
Jorge
J
Benboubker
Lotfi
L
Ohresser
Marc
M
Colombat
Philippe
P
Binet
Chistian
C
Watier
Herve
H
Herault
Olivier
O
D000208:Acute Disease; D001752:Blast Crisis; D001853:Bone Marrow / Q000473:pathology; D002455:Cell Division; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics*; D006801:Humans; D007951:Leukemia, Myeloid / Q000097:blood / Q000235:genetics* / Q000473:pathology*; D011110:Polymorphism, Genetic; D019718:Receptors, CXCR4 / Q000235:genetics; D017154:Stromal Cells / Q000473:pathology*
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D019718:Receptors, CXCR4