Authors:
B. González (México City, MX)
F. Manzanares (México City, MX)
M. Valencia (México City, MX)
H. Flores (México City, MX)
A. Delgado (México City, MX)
G. Sánchez (México City, MX)
D. Senitzer (California, US)
C. Gorodezky (Mexico City. MEXICO, MX)
ALL accounts for >30% of all malignancies diagnosed before the age of 15 years. The disease is multifactorial, and an important role for inherited genetic variation has been suggested for its development. A spectrum of HLA associations were reported and polymorphisms at the killer cell immunoglobulin-like receptors (KIR) influence ALL development as well. KIR genes present on NK cells, regulate their functions through interactions with their HLA ligands, and are also documented to be involved in the destruction of leukemic cells. We addressed this issue by performing a case-control study in Mexican Mestizo patients with ALL, looking for the involvement of KIR3DL1 and its Bw4, A23, A24 & A32 ligands with the development of ALL. DNA was extracted from peripheral blood with the Maxwell16 instrument from 137 patients (90% were children) and 356 healthy controls. KIR3DL1 was detected using a PCR-SSP technique. HLA typing was done using a Luminex PCR-SSOP method. Frequencies of KIR3DL1 and KIR-HLA ligands were compared between patients and controls, using the Chi2 test. A low frequency of 3DL1 in patients vs. controls (80.3% vs. 88.5%; p=0.018; OR=0.530) was shown; however, no difference was observed for Bw4 or for A23, A24 & A32 (p=0.24) or for 3DL1 with any of its ligands (p=0.34). We previously reported protection associated with KIR2DS4 (p=0.002), KIR2DL2 (p=0.001), KIR2DS2 (p=0.0001) and KIR2DS3 (p=0.002) but not KIR3DL1, having typed then, only 66 patients. However, when increasing the number to 137, KIR3DL1 was clearly shown to be a protective gene. We thus conclude, that 3DL1 confers a low risk for ALL development in Mexicans. These data agree with those reported in Chinese populations, but differ from data found in Canadian whites and Indians and in admixed Hispanics from California (which include different races). Activating KIR2DS1-C2, 2DS2-C1 and 3DS1-Bw4 were risk genes in Indians only. Ethnicity differences clearly influence the genetic distribution of KIR genes and their ligands, therefore, probably their associations too. Undoubtedly, KIR3DL1 plays an important role in the expression and clearance of ALL in Mexicans. Moreover, these results are consistent across different ALL phenotypes, as shown in white Canadians. The importance of typing a greater sample size of patients is evident.