The transcription factor MYB is frequently upregulated in T-cell acute lymphoblastic leukemia (T-ALL), a hematological malignancy originating from T-cell precursors. Here, we demonstrate that MYB plays a crucial role by regulating genes essential for T-ALL pathogenesis. Integrative analysis reveals a long MYB isoform, ENST00000367814.8, which is dominantly expressed and confers a proliferative advantage in T-ALL cells. Rapid depletion of MYB via dTAG-mediated protein degradation affects a large number of genes, which can be classified into early response or late response genes based on their kinetics. Early response genes include many genes involved in hematopoiesis, such as TAL1, RUNX1, GATA3, IKZF2, and CXCR4. Their expression can be recovered at later time-points, suggesting the presence of a negative feedback loop mechanism. In contrast, late response genes, which are continuously downregulated after MYB depletion, includes many genes involved in cell proliferation as well as TAL1 targets, thereby affecting the cellular phenotype.

转录因子 MYB 在 T 细胞急性淋巴细胞白血病 （T-ALL） 中经常上调，T-ALL 是一种起源于 T 细胞前体的血液系统恶性肿瘤。在这里，我们证明了 MYB 通过调节 T-ALL 发病机制所必需的基因起关键作用。整合分析揭示了一种长 MYB 亚型 ENST00000367814.8，它在 T-ALL 细胞中显性表达并赋予增殖优势。通过 dTAG 介导的蛋白质降解快速消耗 MYB 会影响大量基因，根据其动力学可分为早期反应基因或晚期反应基因。早期反应基因包括许多参与造血的基因，例如 TAL1、RUNX1、GATA3、IKZF2 和 CXCR4。它们的表达可以在以后的时间点恢复，表明存在负反馈循环机制。相比之下，在 MYB 耗竭后持续下调的迟发反应基因包括许多参与细胞增殖的基因以及 TAL1 靶标，从而影响细胞表型。