Clonal hematopoiesis of indeterminant potential (CHIP) is defined by the acquisition of driver mutations within hematopoietic stem cells (HSCs), that leads to clonal expansions. Factors that determine the extent of clonal expansion in CHIP remain poorly understood. Weinstock et al. developed a method named passenger-approximated clonal expansion rate (PACER) to ascertain clonal fitness. A genome-wide association study of PACER identified a polymorphism in the TCL1A promoter (rs2887399) as a modulator of clonal expansions in individuals with CHIP-associated mutations in ET2, ASXL1, SF3B1 or SRSF2 but not in DNMT3A. The TCL1A promoter is usually inaccessible in healthy hematopoietic stem cells. This repression is alleviated in the presence of certain driver mutations, leading to gene activation and clonal expansion. The common T allele of rs2887399 was associated with more limited de-repression, and clonal expansion of HSCs. These data offer the intriguing possibility that targeting TCL1A pharmacologically might restrain CHIP. Time will tell whether this is the case.

不确定潜能克隆造血 (CHIP) 的定义是造血干细胞 (HSC) 内获得驱动突变，从而导致克隆扩增。决定 CHIP 克隆扩增程度的因素仍知之甚少。温斯托克等人。开发了一种名为乘客近似克隆扩增率（PACER）的方法来确定克隆适应性。PACER 的全基因组关联研究发现，TCL1A启动子 (rs2887399) 中的多态性是在ET2、ASXL1、SF3B1或SRSF2中具有 CHIP 相关突变但在DNMT3A中没有的个体中克隆扩增的调节剂。TCL1A启动子在健康的造血干细胞中通常无法接近。这种抑制在某些驱动突变的存在下得到缓解，导致基因激活和克隆扩张。rs2887399 的常见 T 等位基因与更有限的 HSC 去抑制和克隆扩增相关。这些数据提供了一种有趣的可能性，即在药理学上靶向 TCL1A 可能会抑制 CHIP。时间会证明情况是否如此。