Medical College of Nanchang University, Nanchang, 330000, China; Queen Mary University of London, London, E1 4NS, UK.
Biomed Pharmacother. 2020 Jun;126:110107. doi: 10.1016/j.biopha.2020.110107. Epub 2020 Apr 1.
T-cell prolymphocytic leukemia (T-PLL) is a rare mature T cell leukemia with aggressive clinical course, poor response to conventional therapies and high mortality rates. Classical cytogenetics and various genetic techniques have observed complex karyotypes and associated genes involved in the molecular pathogenesis of T-PLL, among which the proto-oncogene T-cell leukemia/lymphoma 1 (TCL1) as a hallmark of malignancy is hyper-activated and abnormally expressed in many T-PLL cases. Progress has been made to identify the presence of chromosomal rearrangements and subsequent changes in key molecular pathways typically involving Akt, which may hint cytogenetic mechanisms underlying the pathogenesis of T-PLL and indicate new treatment targets. In this article, we describe current insights of T-PLL with an emphasis on the potential role of TCL1 gene disorders and TCL1-Akt interactions in cell transformation and disease progression, followed by discussion on current treatment options and novel therapeutic approaches based on cytogenetics, which still remains to be explored for the effective management of T-PLL and other TCL1-driven hematological malignancies.
T 细胞前淋巴细胞白血病（T-PLL）是一种罕见的成熟 T 细胞白血病，具有侵袭性的临床病程、对常规治疗反应不佳和高死亡率。经典细胞遗传学和各种基因技术观察到复杂的核型和参与 T-PLL 分子发病机制的相关基因，其中原癌基因 T 细胞白血病/淋巴瘤 1（TCL1）作为恶性肿瘤的标志在许多 T-PLL 病例中被过度激活和异常表达。已经取得了进展来识别染色体重排的存在以及随后涉及 Akt 的关键分子途径的变化，这可能暗示 T-PLL 发病机制的细胞遗传学机制，并指出新的治疗靶点。本文描述了 T-PLL 的当前研究进展，重点介绍 TCL1 基因紊乱和 TCL1-Akt 相互作用在细胞转化和疾病进展中的潜在作用，随后讨论了基于细胞遗传学的当前治疗选择和新的治疗方法，这对于有效管理 T-PLL 和其他 TCL1 驱动的血液恶性肿瘤仍然有待探索。
