National Center for Tumor Diseases (NCT), Dresden, Germany.
Pediatric Hematology and Oncology, Department of Pediatrics, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany.
Blood. 2021 Oct 21;138(16):1412-1428. doi: 10.1182/blood.2020009895.
B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is the most common form of childhood cancer. Chemotherapy is associated with life-long health sequelae and fails in ∼20% of cases. Thus, prevention of leukemia would be preferable to treatment. Childhood leukemia frequently starts before birth, during fetal hematopoiesis. A first genetic hit (eg, the ETV6-RUNX1 gene fusion) leads to the expansion of preleukemic B-cell clones, which are detectable in healthy newborn cord blood (up to 5%). These preleukemic clones give rise to clinically overt leukemia in only ∼0.2% of carriers. Experimental evidence suggests that a major driver of conversion from the preleukemic to the leukemic state is exposure to immune challenges. Novel insights have shed light on immune host responses and how they shape the complex interplay between (1) inherited or acquired genetic predispositions, (2) exposure to infection, and (3) abnormal cytokine release from immunologically untrained cells. Here, we integrate the recently emerging concept of "trained immunity" into existing models of childhood BCP-ALL and suggest future avenues toward leukemia prevention.
B 细胞前体急性淋巴细胞白血病 (BCP-ALL) 是儿童中最常见的癌症形式。化疗与终身健康后遗症相关联，并且在大约 20%的病例中失败。因此，预防白血病优于治疗。儿童白血病通常在胎儿造血期间于出生前开始。第一个遗传打击（例如，ETV6-RUNX1 基因融合）导致白血病前 B 细胞克隆的扩增，这些克隆可在健康的新生儿脐带血中检测到（高达 5%）。这些白血病前克隆仅在约 0.2%的携带者中导致临床明显的白血病。实验证据表明，从白血病前状态向白血病状态转化的主要驱动因素是暴露于免疫挑战。新的见解揭示了免疫宿主反应以及它们如何塑造（1）遗传或获得的遗传易感性、（2）感染暴露和（3）免疫未训练细胞异常细胞因子释放之间的复杂相互作用。在这里，我们将最近出现的“训练免疫”概念纳入现有的儿童 BCP-ALL 模型，并提出了预防白血病的未来途径。
