Buono Lorena, Iside Concetta, Pecoraro Giovanni, De Matteo Antonia, Beneduce Giuliana, Penta de Vera d'Aragona Roberta, Parasole Rosanna, Mirabelli Peppino, Vitagliano Luigi, Salvatore Marco, Smaldone Giovanni
IRCCS SYNLAB SDN, Via E. Gianturco 113, 80143 Naples, Italy.
Department of Pediatric Hemato-Oncology, Santobono-Pausilipon Children's Hospital, AORN, 80122 Naples, Italy.
J Clin Med. 2023 May 25;12(11):3669. doi: 10.3390/jcm12113669.
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.
急性白血病是最常见的儿童癌症。在大多数情况下,这种疾病是由B细胞(B-ALL)或较少见的T细胞祖细胞(T-ALL)的恶性转化引起的。最近,在患者和作为体外模型系统的连续细胞系中均检测到钾(K)通道四聚体化结构域含蛋白(KCTDs)这一新兴类别成员KCTD15的明显过表达。由于越来越多的证据表明KCTDs在癌症中发挥着关键但多样的作用,我们在此报告对其在B-ALL和T-ALL患者中的表达谱进行的详尽分析。尽管对于大多数KCTDs而言,在这些病理状态下未发现明显改变,但在转录组分析中,与健康受试者的值相比,该家族的一些成员检测到明显的上调和下调。其中,特别相关的是T-ALL患者中密切相关的KCTD1和KCTD15的上调。有趣的是,KCTD1在未受影响的对照和B-ALL患者中几乎均不表达。因此,该分析不仅代表了第一项在特定病理背景下同时评估所有KCTDs失调情况的研究,还提供了一种有望用于临床的T-ALL生物标志物。