Kawashima Naomi, Gurnari Carmelo, Bravo-Perez Carlos, Kubota Yasuo, Pagliuca Simona, Guarnera Luca, Williams Nakisha D, Durmaz Arda, Ahmed Arooj, Dima Danai, Ullah Fauzia, Carraway Hetty E, Singh Abhay, Visconte Valeria, Maciejewski Jaroslaw P
Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.
Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.
Leukemia. 2025 Feb;39(2):451-459. doi: 10.1038/s41375-024-02460-y. Epub 2024 Nov 21.
Past studies described occasional patients with myeloid neoplasms (MN) and coexistent large granular lymphocytic leukemia (LGLL) or T-cell clonopathy of unknown significance (TCUS), which may represent expansion of myeloid clonal hematopoiesis (CH) as triggers or targets of clonal cytotoxic T cell reactions. We retrospectively analyzed 349 LGLL/TCUS patients, 672 MN patients, and 1443 CH individuals to establish the incidence, genetic landscape, and clinical phenotypes of CH in LGLL. We identified 8% of cases overlapping with MN, while CH was found in an additional 19% of cases (CH + /LGLL) of which TET2 (23%) and DNMT3A (14%) were the most common. In MN cohort, 3% of cases showed coexistent LGLL. The incidence of CH in LGLL was exceedingly higher than age-matched CH controls (P < 0.0001). By multivariate analysis, the presence of CH in LGLL (P = 0.026) was an independent risk factor for cytopenia in addition to older age (P = 0.003), splenomegaly (P = 0.015) and STAT3/5B mutations (P = 0.001). CH + /LGLL cases also showed a higher progression rate to MN than CH-/LGLL (10% vs. 2% at 5 years; P = 0.02). A close relationship between CH and LGLL suggests that cytopenia in LGLL may be not only related to LGLL but be also secondary to coexisting clonal cytopenia of unclear significance.
既往研究描述了偶见的骨髓肿瘤（MN）患者合并大颗粒淋巴细胞白血病（LGLL）或意义未明的T细胞克隆病（TCUS），这可能代表髓系克隆性造血（CH）的扩增是克隆性细胞毒性T细胞反应的触发因素或靶点。我们回顾性分析了349例LGLL/TCUS患者、672例MN患者和1443例CH个体，以确定LGLL中CH的发病率、基因图谱和临床表型。我们发现8%的病例与MN重叠，而在另外19%的病例（CH+/LGLL）中发现了CH，其中TET2（23%）和DNMT3A（14%）最为常见。在MN队列中，3%的病例显示合并LGLL。LGLL中CH的发病率显著高于年龄匹配的CH对照（P<0.0001）。多因素分析显示，除年龄较大（P=0.003）、脾肿大（P=0.015）和STAT3/5B突变（P=0.001）外，LGLL中CH的存在（P=0.026）是血细胞减少的独立危险因素。CH+/LGLL病例向MN进展的发生率也高于CH-/LGLL（5年时分别为10%和2%；P=0.02）。CH与LGLL之间的密切关系表明，LGLL中的血细胞减少可能不仅与LGLL有关，还继发于意义不明的共存克隆性血细胞减少。
