A Comprehensive Analysis of the Expression Profiles of KCTD Proteins in Acute Lymphoblastic Leukemia: Evidence of Selective Expression of KCTD1 in T-ALL

SIMPLE SUMMARY: Acute lymphoblastic leukemia is the most frequent tumor in childhood age. Recently, we associated KCTD protein family members with childhood ALL with particular reference to B-ALL. In this scenario, our aim was to assess the expression landscape of all KCTD family members in pediatric B-cell and T-cell leukemias compared with mononuclear cells derived from cord blood samples from healthy subjects. Our data allowed us to identify the KCTD1 protein as a potential new biomarker of T-ALL, raising interest for future clinical investigations and validating its role not only as a diagnostic marker, but also as a new potential therapeutic target. ABSTRACT: Acute leukemia is the most common pediatric cancer. In most cases, this disease results from the malignant transformation of either the B-cell (B-ALL) or, less frequently, T-cell progenitors (T-ALL). Recently, a marked overexpression of KCTD15, a member of the emerging class of the potassium (K) channel tetramerization domain-containing proteins (KCTDs) has been detected in both patients and continuous cell lines as in vitro model systems. Because there is growing evidence of the key, yet diversified, roles played by KCTDs in cancers, we here report an exhaustive analysis of their expression profiles in both B-ALL and T-ALL patients. Although for most KCTDs, no significant alterations were found in these pathological states, for some members of the family, significant up- and down-regulations were detected in comparison with the values found in healthy subjects in the transcriptome analysis. Among these, particularly relevant is the upregulation of the closely related KCTD1 and KCTD15 in T-ALL patients. Interestingly, KCTD1 is barely expressed in both unaffected controls and B-ALL patients. Therefore, not only does this analysis represent the first study in which the dysregulation of all KCTDs is simultaneously evaluated in specific pathological contexts, but it also provides a promising T-ALL biomarker that could be suitable for clinical applications.