Many transcription factors (TFs) function as tumor suppressor genes with heterozygous phenotypes, yet haploinsufficiency generally has an underappreciated role in neoplasia. This is no less true in myeloid cells, which are normally regulated by a delicately balanced and interconnected transcriptional network. Detailed understanding of TF dose in this circuitry sheds light on the leukemic transcriptome. In this review, we discuss the emerging features of haploinsufficient transcription factors (HITFs). We posit that: ( a) monoallelic and biallelic losses can have distinct cellular outcomes; ( b) the activity of a TF exists in a greater range than the traditional Mendelian genetic doses; and ( c) how a TF is deleted or mutated impacts the cellular phenotype. The net effect of a HITF is a myeloid differentiation block and increased intercellular heterogeneity in the course of myeloid neoplasia.

中文翻译：

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髓系肿瘤中单倍体不足的转录因子


许多转录因子 （TFs） 作为具有杂合子表型的肿瘤抑制基因发挥作用，但单倍体不足通常在肿瘤形成中的作用被低估。在髓系细胞中也是如此，髓系细胞通常由微妙平衡和互连的转录网络调节。在该回路中详细了解 TF 剂量有助于阐明白血病转录组。在这篇综述中，我们讨论了单倍体不足转录因子 （HITFs） 的新兴特征。我们假设：（a） 单等位基因和双等位基因丢失可以具有不同的细胞结果;（b） TF 的活性存在于比传统孟德尔遗传剂量更大的范围内;（ c） TF 的缺失或突变如何影响细胞表型。HITF 的净效应是髓系分化阻断和髓系肿瘤病程中细胞间异质性增加。