Department of Genetics, Ribeirão Preto Medical School/University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil.
Department of Pediatrics, Ribeirão Preto Medical School/University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil.
Clin Med Insights Oncol. 2014 Aug 24;8:95-100. doi: 10.4137/CMO.S10242. eCollection 2014.
Great improvements have been made in acute lymphoblastic leukemia (ALL) treatment in the past decades, especially due to the use of l-asparaginase (l-ASP). Despite the significant success rate, several side effects mainly caused by toxicity, asparaginase silent inactivation, and cellular resistance, encourage an open debate regarding the optimal dosage and formulation of l-ASP. Alternative sources of asparaginases have been constantly investigated in order to overcome hypersensitivity clinical toxicity. Additionally, genomic modulation as gene expression profiling, genetic polymorphisms, and epigenetic changes is also being investigated concerning their role in cellular resistance to l-ASP. Understanding the mechanisms that mediate the resistance to l-ASP treatment may bring new insights into ALL pathobiology and contribute to the development of more effective treatment strategies. In summary, this review presents an overview on l-ASP data and focuses on cellular mechanisms underlying resistance and alternative therapies for the use of asparaginase in childhood ALL treatment.
在过去的几十年中，急性淋巴细胞白血病（ALL）的治疗取得了重大进展，特别是由于使用了 L-天冬酰胺酶（l-ASP）。尽管成功率显著，但由于毒性、天冬酰胺酶沉默失活和细胞耐药性等几个主要副作用，人们对 l-ASP 的最佳剂量和制剂仍存在争议。为了克服过敏反应的临床毒性，人们一直在不断寻找替代来源的天冬酰胺酶。此外，还研究了基因组调节，如基因表达谱、遗传多态性和表观遗传变化，以了解它们在细胞对 l-ASP 耐药性中的作用。了解介导对 l-ASP 治疗耐药性的机制可能会为 ALL 的病理生物学带来新的见解，并有助于开发更有效的治疗策略。总之，本文综述了 l-ASP 的相关数据，并重点介绍了细胞耐药性的机制以及用于儿童 ALL 治疗的替代天冬酰胺酶疗法。
