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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骨髓肿瘤中单倍体转录因子不足


许多转录因子（TF）充当具有杂合表型的肿瘤抑制基因，但单倍体不足在肿瘤形成中的作用通常未被充分认识。对于骨髓细胞来说也是如此，骨髓细胞通常受到微妙平衡和相互关联的转录网络的调节。详细了解该电路中的 TF 剂量有助于了解白血病转录组。在这篇综述中，我们讨论了单倍体不足转录因子（HITF）的新特征。我们假设：（a）单等位基因和双等位基因的丢失可以产生不同的细胞结果； (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) 转录因子删除或突变如何影响细胞表型。 HITF 的净效应是在髓系肿瘤形成过程中阻碍髓系分化并增加细胞间异质性。