Sal-Like Protein 4 Transcription Factor: A Significant Diagnostic Biomarker Involved in Childhood ALL Resistance and Relapse.

PURPOSE

() is a stem cell transcription factor that plays an essential role in the maintenance and self-renewal of embryonic and hematopoietic stem cells, functioning as an oncogene in several cancers. However, the role of in the biological behavior of childhood acute lymphoblastic leukemia and its relationship with multidrug resistance and relapse has remained largely unknown.

PATIENTS AND METHODS

Quantitative real-time polymerase chain reaction (qRT-PCR) was used to characterize the expression pattern of in the bone marrow samples of 43 patients with Philadelphia negative ALL and 18 children in the non-cancer control group. The presence of minimal residual disease was measured a year after the initial therapy using SSCP (single-strand conformation polymorphism). In addition, the correlation between the expression of and in relapsed patients was analyzed statistically.

RESULTS

Results showed an overexpression of in de novo patients compared with the control group (=0.0001, AUC= 0.93), indicating the importance of this gene in the induction of leukemia. A significant increase in the ABCA3 expression levels was revealed in the relapsed patients, in comparison with the drug-sensitive group ( = 0.0005). The leukemogenetic effect of can be related to the effect of this gene on the maintenance of pluripotency in cancer stem cells. Results also suggest that the expression of can be considered as a diagnostic marker for pediatric ALL. Moreover, expression levels in the minimal residual disease positive (mrd+) ALL group was significantly higher than those in the mrd- group (p=0.0001, AUC= 0.92).

CONCLUSION

These data demonstrate the prognostic impact of in childhood ALL. Our findings also indicated a direct correlation between the mRNA expression levels of and transporter in the relapsed group of ALL patients (r=0.7). These results describe a possible mechanism by which may lead to the development of multidrug resistance.