Study on the Phenotype Polymorphism of CYP3A4 Gene in Chinese Children with Acute Leukemia.

In order to offer objective refering paramete for individualized chemotherapy, to clarify the distribution feature of CYP3A4 activity in Chinese children with acute leukemia and in healthy children, to explore the possible correlation between the activity of CYP3A4 gene and the predisposition or chemotherapy effect in acute leukemia children. High performance liquid chromatography (HPLC) was used to detecte the activity of CYP3A4 in 85 healthy children and 120 acute leukemia children, then analyzed the difference of phenotypebetween two groups. The activity coverage of CYP3A4 was 2.34~48.88 in healthy children and the average activity was 9.76±6.99. Among them, CYP3A4 activity was 11.88±8.88 in male group and 7.12±3.37 in female group, the former was obviously higher than the latter (P=0.0077). In less than 12-years group, CYP3A4 activity was 8.97±6.27, while it was 10.43±7.74 in more than 12-years group, there was no significant difference (P>0.05). The change scope of CYP3A4 activity was very large in children with acute lymphoblastic leukemia, from 2.00 to 585.72, the average activity was 53.52, with no dfference in sex and age. According to the clinical risk degree, the activity of CYP3A4 was 4.87±2.93 in standard-risk group, it was 31.63±19.20 in middle-risk group, the latter was significantly higher thanthe former (P=0.0004). Comparison based on WBC count at the beginning of preliminary diagnosis, the CYP3A4 activity was the lowest in WBC count less than 50 x 10⁹/L group, it was second in the group of WBC count between 50 x 10⁹/L to 100 x 10⁹/L, and the activity was the highest in WBC count more than 100 x 10⁹/L group. The mean activity of CYP3A4 in childern with acute lymphoblastic leukemia with P170 less than 5% was 17.56±13.44, while it was 87.62±49.28 in those children with P170 more than 5%Ä, there was statistic difference between the two group(P=0.022). The activity in those preliminary diagnosed children with BCR-ABL(+) or Ph (+) or t (4,11) abnormal karyotype (105.86±44.41) was higher than those with normal karyotype patients (47.61±22.63), P=0.0219. Comparison the activity of CYP3A4 between those chlidren with clinical presentation as prednisone good response (PGR) and those with prednisone poor response, the activity in former group (27.23±13.58) was obviously lower than that of latter group (114.12±48.39), P=0.0358. The average CYP3A4 activity in children with acute myelocytic leukemia (AML) was 13.97±10.84. Of them, it was 15.09±7.52 in AML children with diploid chromosome and only 2.95±1.39 in hypodiploidy group, obviously, the activity of former group higher than that of latter group (P=0.0132). The CYP3A4 activity was respectively 19.78±11.59 and 2.86±1.16 in normal LDH group and in increased LDH group, there was significant difference (P=0.0036). The AML children with exo-marrow infiltration when diagnosis, their CYP3A4 activity (6.50±3.05) was lower than those children with pure marrow infiltration (19.06±11.15), P=0.044. There may be no race difference between the CYP3A4 activity of Chinese healthy children and White people. Increased CYP3A4 activity has closed correlation with ALL risk factors. The general CYP3A4 activity in AML children group was lower than that of ALL chlidren group. Much higher or much lower CYP3A4 activity may produce adverse influence to individuals.