| ObjectiveTo study the expression of caudal-related homeodomain transcription 2 (CDX2) gene in Childhood Leukemia and its clinical implications , as well as the comparison with those of Wilms'tumor 1 (WT1) gene.MothedsBoth of the genes were detected by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) in the bone marrow(BM) and peripheral blood(PB) samples of 60 cases of childhood leukemia---39 cases of non-remission AL concluded by 35 cases of the newly diagnosed (25 cases of ALL, 10 cases of AML) and 4 cases of the relapsed,18 cases of the remission as well as 3 cases of CML. In addition ,17 cases of adult leukemia (5 cases of ALL,8 cases of AML,3 cases of CML and 1 case of CLL) and 25 cases of healthy people were enrolled as control. By following up 11 cases of AL patients for eight to thirteen months ,with the same time detection on the expression level of CDX2 and WT1 during different periods of treatment ,we intend to compare and analyse the two genes'role in MRD detection and ultimately predict the fisibility of MRD detection by using CDX2.Results1. The expression of CDX2 in the newly diagnosed leukemia of the children group and adult group.In 38 cases of the newly diagnosed leukemia children,the overexpression of CDX2 was found in 28, with the total positive rate being 80.0%(28/35)in acute leukemia(AL),and to be exact, the positive rate being 88.0% in acute lymphocytic leukemia(ALL) and 60.0% in acute myeloid leukemia (AML) ,which showed no statistical difference (P =0.084, P >0.05), and so was the expression level (0.6181±0.2342 vs 0.6230±0.2441) between the two group (t=0.055,P >0.05);CDX2 was also detectable in 1 of 3 chronic myeloid leukemia (CML) patients. In 17 cases of adult leukemia, the overexpression of CDX2 was found in 69.2% (9/13)AL, 1/3 CML and 1/1 chronic lymphocytic leukemia (CLL). The positive rates of CDX2 in AL between children group and adult group (80.0% vs 69.2%)are no statistically difference(P =0.334,P >0.05), and so was the expression level (0.5910±0.2225 vs 0.5981±0.2862) between the two group (t=0.025,P >0.05); those in AML (60.0% vs 87.5% ) are no statistically difference as well(P =0.225,P >0.05), while those in ALL(88.0% vs 40%)are statistically significant difference. Compared with children AL group ,CDX2 gene was negatively expressed in all the 25 samples of healthy people, which revealed statistically significant difference ( =37.5, P <0.005<0.01),and the expression level of CDX2 in AL,ALL and AML was much highe(r0.5910±0.2225,0.6181±0.2342,0.6230±0.2441).The expression level of CDX2 in the newly diagnosed AL group was lower than that in the relapsed group(0.5910±0.2225 vs 0.7733±0.0465)(t=2.912, P <0.05).2.Comparison of positive rate between CDX2 and WT1 in pediatric AL.In childhood AL, the positive rates of CDX2 between non-remission group and remission group (82.1% vs 0%) had statistically significant difference( =33.67, P <0.005<0.01);those between non-remission group and control group (82.1% vs 0%) also showed statistically significant difference( =41, P <0.01);those between ALL group and AML group in the non-remission (89.3% vs 63.6%) were no statistically difference(P=0.083,P>0.05). The positive rates between CDX2 and WT1 in non-remission group (48.7% vs 82.1%) had statistically significant difference(P=0.049,P<0.05),those in ALL group (46.4% vs 89.3%) also showed statistically significant difference(P<0.05),while those in AML group(54.5% vs 63.6%) were no statistically difference(P<0.05).3.The significances of CDX2,WT1 in clinical response to treatment.In the newly diagnosed AL children, rates of complete remission(CR) in the CDX2 positively expressed patients and negatively expressed ones (96.4% vs 100%) showed no statistically difference (P>0.05),CR rates between CDX2 and WT1 negtively expressed patients were no statistically difference (P>0.05),and so was the two in positively expressed groups (P>0.05).For CDX2 and WT1,the comparison of CR rates between the double positive group and the double negative group was no statistically difference (P>0.05), and so were the both positive group and the single positive group (P>0.05), the single positive group and the double negative group (P>0.05). All of patients achieved CR except one double positive expressed patient who was nominated as high risk for reaching no CR at the chemotherapy day of 19th and termination of induction.4. The correlation between the expression of CDX2 and that of WT1 in children ALIn the CDX2 positively and negatively expressed patients, positive rates of WT1 were 46.7%(15/32)and 57.1%(4/7),which suggested no statistically correlation between the expression of CDX2 and that of WT1 in children AL.5.The dynamic monitoring of CDX2 during the progression of ALNine newly diagnosed AL patients with positive CDX2 expression were followed up for 8 to 14 months. CDX2 in 5 patients gradually turned negative during day 13～19 and the remained four turned negative after induction. However, in CDX2 negatively expressed AL patients,CDX2 remained negative at CR till present. In 7 WT1 positively expressed patients, 5 of them turned WT1-negative during day 13～19, one of the other 2 turned WT1-negative after induction, the expression level of WT1 in the remaining one decreaced significantly but didn't turned negative. All of them have kept CR till now.6.Comparison of the CDX2 expression in BM and PBDetecting samples of BM and PB from the same period of 9 newly diagnosed AL patients by semi-quantitative RT-PCR, the average CDX2 expression level was (0.4083±0.2279),(0.4124±0.1749),the comparison was no statistically difference(t= 0.0428,P>0.05).Conclusion1. CDX2 gene is highly expressed in the overwhelming children with AL and with CL, which is similar to adults with leukemia.2. In children with AL and ALL, positive rates of CDX2 are significantly higher than those of WT1, the expressions of CDX2 and WT1 have no correlation.3. Expression of CDX2 has no relation with the responses to treatment in AL and this value shows no significant difference between CDX2 and WT1.4. CDX2 gene to some extent has direct relation with the load of leukemia cells as progression and it shows a certain significance in MRD detection, which might be of better value than WT1 in the field of childhood leukemia.5. To detect CDX2 expression by using PB sample instead of BM in newly diagnosed patients is feasible. |
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