Schmied Laurent, Olofsen Patricia A, Lundberg Pontus, Tzankov Alexandar, Kleber Martina, Halter Jörg, Uhr Mario, Valk Peter J M, Touw Ivo P, Passweg Jakob, Drexler Beatrice
Division of Hematology and.
Division of Internal Medicine, University Hospital Basel, Basel, Switzerland.
Blood Adv. 2020 Nov 10;4(21):5540-5546. doi: 10.1182/bloodadvances.2020001541.
Acquired aplastic anemia and severe congenital neutropenia (SCN) are bone marrow (BM) failure syndromes of different origin, however, they share a common risk for secondary leukemic transformation. Here, we present a patient with severe aplastic anemia (SAA) evolving to secondary chronic neutrophilic leukemia (CNL; SAA-CNL). We show that SAA-CNL shares multiple somatic driver mutations in CSF3R, RUNX1, and EZH2/SUZ12 with cases of SCN that transformed to myelodysplastic syndrome or acute myeloid leukemia (AML). This molecular connection between SAA-CNL and SCN progressing to AML (SCN-AML) prompted us to perform a comparative transcriptome analysis on nonleukemic CD34high hematopoietic stem and progenitor cells, which showed transcriptional profiles that resemble indicative of interferon-driven proinflammatory responses. These findings provide further insights in the mechanisms underlying leukemic transformation in BM failure syndromes.
获得性再生障碍性贫血和严重先天性中性粒细胞减少症（SCN）是起源不同的骨髓（BM）衰竭综合征，然而，它们具有继发性白血病转化的共同风险。在此，我们报告一名严重再生障碍性贫血（SAA）演变为继发性慢性中性粒细胞白血病（CNL；SAA-CNL）的患者。我们发现，SAA-CNL与转化为骨髓增生异常综合征或急性髓系白血病（AML）的SCN病例在CSF3R、RUNX1和EZH2/SUZ12中存在多个体细胞驱动突变。SAA-CNL与进展为AML的SCN（SCN-AML）之间的这种分子联系促使我们对非白血病性CD34高造血干细胞和祖细胞进行比较转录组分析，结果显示转录谱类似于干扰素驱动的促炎反应。这些发现为骨髓衰竭综合征中白血病转化的潜在机制提供了进一步的见解。
