大颗粒淋巴细胞白血病中的克隆性造血
Clonal hematopoiesis in large granular lymphocytic leukemia.
作者信息
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
机构信息
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.
出版信息
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。