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IKZF1 在 B 细胞前体急性淋巴细胞白血病中的多面性。

The many faces of IKZF1 in B-cell precursor acute lymphoblastic leukemia.

机构信息

Laboratory of Pediatric Oncology, Radboud University Medical Center, Nijmegen, the Netherlands.

Laboratory of Pediatric Oncology, Radboud University Medical Center, Nijmegen, the Netherlands

出版信息

Haematologica. 2018 Apr;103(4):565-574. doi: 10.3324/haematol.2017.185603. Epub 2018 Mar 8.

Abstract

Transcription factor IKZF1 (IKAROS) acts as a critical regulator of lymphoid differentiation and is frequently deleted or mutated in B-cell precursor acute lymphoblastic leukemia. gene defects are associated with inferior treatment outcome in both childhood and adult B-cell precursor acute lymphoblastic leukemia and occur in more than 70% of -positive and -like cases of acute lymphoblastic leukemia. Over the past few years, much has been learned about the tumor suppressive function of IKZF1 during leukemia development and the molecular pathways that relate to its impact on treatment outcome. In this review, we provide a concise overview on the role of IKZF1 during normal lymphopoiesis and the pathways that contribute to leukemia pathogenesis as a consequence of altered IKZF1 function. Furthermore, we discuss different mechanisms by which alterations impose therapy resistance on leukemic cells, including enhanced cell adhesion and modulation of glucocorticoid response.

摘要

转录因子 IKZF1(IKAROS)是淋巴样分化的关键调节因子,在 B 细胞前体急性淋巴细胞白血病中经常缺失或突变。IKZF1 基因缺陷与儿童和成人 B 细胞前体急性淋巴细胞白血病的治疗效果差相关,并且发生在超过 70%的阳性和类似急性淋巴细胞白血病病例中。在过去的几年中,人们已经了解了 IKZF1 在白血病发生过程中的肿瘤抑制功能以及与其对治疗结果影响相关的分子途径。在这篇综述中,我们简要概述了 IKZF1 在正常淋巴生成过程中的作用,以及由于 IKZF1 功能改变而导致白血病发病机制的途径。此外,我们还讨论了改变如何通过增强细胞黏附和调节糖皮质激素反应等不同机制赋予白血病细胞对治疗的抗性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7c7/5865415/4c4edfd7f578/103565.fig1.jpg

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