Howard Hughes Medical Institute and Department of Pathology, New York University School of Medicine, New York, NY;
Blood. 2014 Apr 17;123(16):2451-9. doi: 10.1182/blood-2013-08-355818. Epub 2014 Mar 7.
The Notch signaling pathway is a regulator of self-renewal and differentiation in several tissues and cell types. Notch is a binary cell-fate determinant, and its hyperactivation has been implicated as oncogenic in several cancers including breast cancer and T-cell acute lymphoblastic leukemia (T-ALL). Recently, several studies also unraveled tumor-suppressor roles for Notch signaling in different tissues, including tissues where it was before recognized as an oncogene in specific lineages. Whereas involvement of Notch as an oncogene in several lymphoid malignancies (T-ALL, B-chronic lymphocytic leukemia, splenic marginal zone lymphoma) is well characterized, there is growing evidence involving Notch signaling as a tumor suppressor in myeloid malignancies. It therefore appears that Notch signaling pathway's oncogenic or tumor-suppressor abilities are highly context dependent. In this review, we summarize and discuss latest advances in the understanding of this dual role in hematopoiesis and the possible consequences for the treatment of hematologic malignancies.
Notch 信号通路是几种组织和细胞类型中自我更新和分化的调节因子。Notch 是一种二元细胞命运决定因子，其过度激活已被认为与几种癌症（包括乳腺癌和 T 细胞急性淋巴细胞白血病（T-ALL））的致癌有关。最近，几项研究还揭示了 Notch 信号在不同组织中的肿瘤抑制作用，包括在特定谱系中以前被认为是癌基因的组织。虽然 Notch 作为几种淋巴恶性肿瘤（T-ALL、B 慢性淋巴细胞白血病、脾边缘区淋巴瘤）的癌基因的参与已得到很好的描述，但越来越多的证据表明 Notch 信号作为髓系恶性肿瘤的肿瘤抑制因子。因此，Notch 信号通路的致癌或肿瘤抑制能力似乎高度依赖于上下文。在这篇综述中，我们总结并讨论了在造血过程中对这种双重作用的最新认识，以及对血液恶性肿瘤治疗的可能影响。
