Anna Østergaard, Judith M Boer, Frank N van Leeuwen, Rob Pieters, Monique L Den Boer
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引用次数: 0
摘要
急性淋巴细胞白血病(ALL)是儿童和青少年中最常见的恶性肿瘤,近几十年来,儿童的存活率已上升到90%以上,这主要归功于风险适应疗法的引入。因此,了解影响复发风险的因素非常重要。转录因子IKAROS是淋巴细胞发育的调节因子,其编码基因IKZF1的改变在ALL中很常见,并与较高的复发风险相关。这篇简明综述将讨论 IKAROS 的正常功能,以及基因改变对 ALL 的影响,如能量限制的缓解和对抗白血病药物反应的改变。除了生物学方面,还将讨论基因改变对不同亚型 ALL 的临床影响。最后,还将探讨治疗IKZF1基因改变的ALL的可能性,包括细胞信号抑制剂和免疫疗法等新型疗法。
IKZF1 in acute lymphoblastic leukemia: the rise before the fall?
Acute lymphoblastic leukemia (ALL) is the most common malignancy in children and adolescents and in recent decades, the survival rates have risen to >90% in children largely due the introduction of risk adapted therapy. Therefore, knowledge of factors influencing risk of relapse is important. The transcription factor IKAROS is a regulator of lymphocyte development and alterations of its coding gene, IKZF1, are frequent in ALL and are associated with higher relapse risk. This concise review will discuss the normal function of IKAROS together with the effect of gene alterations in ALL such as relieved energy restriction and altered response to anti-leukemic drugs. Besides the biology, the clinical impact of gene alterations in the different subtypes of ALL will be discussed. Finally, possibilities for treating ALL with IKZF1 alterations will be considered including novel therapies like cell signaling inhibitors and immunotherapy.
期刊介绍:
Leukemia & Lymphoma in its fourth decade continues to provide an international forum for publication of high quality clinical, translational, and basic science research, and original observations relating to all aspects of hematological malignancies. The scope ranges from clinical and clinico-pathological investigations to fundamental research in disease biology, mechanisms of action of novel agents, development of combination chemotherapy, pharmacology and pharmacogenomics as well as ethics and epidemiology. Submissions of unique clinical observations or confirmatory studies are considered and published as Letters to the Editor