TLE1 as an indicator of adverse prognosis in pediatric acute lymphoblastic leukemia.

Purpose: Acute lymphoblastic leukemia (ALL) is the most common type of cancer in children, and despite the high rate of cure (over 80%) it still has a big impact on morbidity and mortality. The Transducin-like enhancer of split 1 (TLE1), a transcriptional corepressor, has been described as dysregulated and recently emerged as a tumor marker in several cancer types, including hematologic malignancies.

Methods: In the present study TLE1 gene expression was evaluated by RT-qPCR. A total of 60 consecutive pathological ALL samples and 8 normal bone marrow samples were included. Associations between TLE1 levels and clinicopathological features were estimated using Mann-Whitney tests.

Results: TLE1 mRNA levels were significantly diminished in ALL samples when compared to normal counterparts (fold change -1.45, p-value 0.039). Lower TLE1 expression levels were associated with poorer prognostic features such as age at diagnosis (<1 or >9 years-old), absence of the Common Acute Lymphoblastic Leukemia Antigen (CALLA) and high white cell count. Considering immunophenotype, decreased expression of TLE1 was only evident for T-cell ALL, what was validated using gene expression profiling data available in public repositories. No associations with event or overall survival were observed. However, TLE1 expression was statistically different between patients who achieved complete clinical remission (CCR) from those that relapsed or died.

Conclusion: These data are of particular interest and give support for a plausible role of TLE1 as a tumor suppressor in T-cell ALL. Moreover, the prognostic value of this corepressor may assist ALL treatment stratification and suggest the need of alternative regimens.