Clonal hematopoiesis in large granular lymphocytic leukemia

IF 12.8 1区 医学 Q1 HEMATOLOGY
Naomi Kawashima, Carmelo Gurnari, Carlos Bravo-Perez, Yasuo Kubota, Simona Pagliuca, Luca Guarnera, Nakisha D. Williams, Arda Durmaz, Arooj Ahmed, Danai Dima, Fauzia Ullah, Hetty E. Carraway, Abhay Singh, Valeria Visconte, Jaroslaw P. Maciejewski
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Abstract

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.

Abstract Image

大颗粒淋巴细胞白血病中的克隆性造血
过去的研究描述了偶尔出现的骨髓性肿瘤(MN)和大颗粒淋巴细胞白血病(LGLL)或意义不明的 T 细胞克隆病(TCUS)并存的患者,这可能代表骨髓克隆性造血(CH)的扩展,是克隆性细胞毒性 T 细胞反应的诱因或目标。我们对 349 例 LGLL/TCUS 患者、672 例 MN 患者和 1443 例 CH 患者进行了回顾性分析,以确定 CH 在 LGLL 中的发病率、遗传情况和临床表型。我们发现有 8% 的病例与 MN 重叠,另有 19% 的病例(CH + /LGLL)发现了 CH,其中最常见的是 TET2(23%)和 DNMT3A(14%)。在MN队列中,3%的病例同时存在LGLL。LGLL 中 CH 的发病率远远高于年龄匹配的 CH 对照组(P < 0.0001)。通过多变量分析,除年龄较大(P = 0.003)、脾脏肿大(P = 0.015)和 STAT3/5B 突变(P = 0.001)外,LGLL 中存在 CH(P = 0.026)也是导致全血细胞减少的独立危险因素。CH + /LGLL病例的MN进展率也高于CH-/LGLL病例(5年时10%对2%;P = 0.02)。CH 和 LGLL 之间的密切关系表明,LGLL 中的全血细胞减少症可能不仅与 LGLL 有关,还可能继发于并存的克隆性全血细胞减少症,但其意义并不明确。
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来源期刊
Leukemia
Leukemia 医学-血液学
CiteScore
18.10
自引率
3.50%
发文量
270
审稿时长
3-6 weeks
期刊介绍: Title: Leukemia Journal Overview: Publishes high-quality, peer-reviewed research Covers all aspects of research and treatment of leukemia and allied diseases Includes studies of normal hemopoiesis due to comparative relevance Topics of Interest: Oncogenes Growth factors Stem cells Leukemia genomics Cell cycle Signal transduction Molecular targets for therapy And more Content Types: Original research articles Reviews Letters Correspondence Comments elaborating on significant advances and covering topical issues
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