Division of Pediatric Hematology-Oncology, Charles-Bruneau Cancer Center, CHU Sainte-Justine, Montréal, Québec, Canada.
Division of Pediatric Hematology-Oncology, Charles-Bruneau Cancer Center, CHU Sainte-Justine, Montréal, Québec, Canada.
Blood Rev. 2020 Nov;44:100677. doi: 10.1016/j.blre.2020.100677. Epub 2020 Mar 31.
Advances in genomics have deepened our understanding of the biology of acute lymphoblastic leukemia (ALL), defined novel molecular leukemia subtypes, discovered new prognostic biomarkers and paved the way to emerging molecularly targeted therapeutic avenues. Since its discovery, IKZF1 has generated significant interest within the leukemia scientific community.IKZF1 plays a critical role in lymphoid development and its alterations cooperate to mediate leukemogenesis. IKZF1 alterations are present in approximately 15% of childhood ALL, rise in prevalence among adults with ALL and become highly enriched within kinase-driven ALL. A cumulating body of literature has highlighted the adverse prognostic impact of IKZF1 alterations in both Philadelphia chromosome (Ph)-negative and Ph-driven ALL. IKZF1 alterations thus emerge as an important prognostic biomarker in ALL. This article aims to provide a state-of-the-art review focusing on the prognostic clinical relevance of IKZF1 alterations in ALL, as well as current and future therapeutic strategies targeting IKZF1-altered ALL.
基因组学的进展加深了我们对急性淋巴细胞白血病 (ALL) 生物学的理解，定义了新的分子白血病亚型，发现了新的预后生物标志物，并为新兴的分子靶向治疗方法铺平了道路。自发现以来，IKZF1 在白血病科学界引起了极大的兴趣。IKZF1 在淋巴样发育中发挥着关键作用，其改变共同介导白血病的发生。大约 15%的儿童 ALL 存在 IKZF1 改变，成人 ALL 中的发病率上升，并且在激酶驱动的 ALL 中高度富集。越来越多的文献强调了 IKZF1 改变在费城染色体 (Ph)-阴性和 Ph 驱动的 ALL 中的不良预后影响。因此，IKZF1 改变成为 ALL 中的一个重要预后生物标志物。本文旨在提供一篇最新的综述，重点关注 IKZF1 改变在 ALL 中的预后临床相关性，以及针对 IKZF1 改变的 ALL 的当前和未来治疗策略。
