Discrete genetic subtypes and tumor microenvironment signatures correlate with peripheral T-cell lymphoma outcomes: LYMPHOMA

被引：0

作者：

Suehara, Yasuhito ^{[1
,2
]}

Sakamoto, Kana ^{[3
,4
]}

Fujisawa, Manabu ^{[2
,5
]}

Fukumoto, Kota ^{[1
]}

Abe, Yoshiaki ^{[1
,2
]}

Makishima, Kenichi ^{[1
]}

Suma, Sakurako ^{[1
]}

Sakamoto, Tatsuhiro ^{[1
,2
]}

Hattori, Keiichiro ^{[1
,2
]}

Sugio, Takeshi ^{[6
,7
]}

Kato, Koji ^{[6
]}

Akashi, Koichi ^{[6
]}

Matsue, Kosei ^{[8
]}

Narita, Kentaro ^{[3
,4
]}

Takeuchi, Kengo ^{[3
,4
,9
]}

Carreras, Joaquim ^{[10
]}

Nakamura, Naoya ^{[10
]}

Chiba, Kenichi ^{[11
]}

Shiraishi, Yuichi ^{[11
]}

Miyano, Satoru ^{[12
]}

Ogawa, Seishi ^{[13
,14
]}

Chiba, Shigeru ^{[1
,2
]}

Sakata-Yanagimoto, Mamiko ^{[1
,2
,15
]}

机构：

[1] Univ Tsukuba Hosp, Dept Hematol, Tsukuba, Japan

[2] Univ Tsukuba, Inst Med, Dept Hematol, Tsukuba, Japan

[3] Japanese Fdn Canc Res, Canc Inst, Pathol Project Mol Targets, Tokyo, Japan

[4] Japanese Fdn Canc Res, Canc Inst, Div Pathol, Tokyo, Japan

[5] BC Canc, Ctr Lymphoid Canc Dept, Vancouver, BC, Canada

[6] Kyushu Univ, Grad Sch Med Sci, Dept Med & Biosyst Sci, Fukuoka, Japan

[7] Stanford Univ, Dept Med, Div Oncol, Stanford, CA USA

[8] Kameda Med Ctr, Dept Internal Med, Div Hematol Oncol, Kamogawa, Japan

[9] Japanese Fdn Canc Res, Canc Inst Hosp, Dept Pathol, Tokyo, Japan

[10] Tokai Univ, Sch Med, Dept Pathol, Isehara, Japan

[11] Natl Canc Ctr, Res Inst, Tokyo, Japan

[12] Tokyo Med & Dent Univ, M&D Data Sci Ctr, Tokyo, Japan

[13] Kyoto Univ, Dept Pathol & Tumor Biol, Kyoto, Japan

[14] Kyoto Univ, Inst Adv Study Human Biol WPI ASHBi, Kyoto, Japan

[15] Univ Tsukuba, Transborder Med Res Ctr, Div Adv Hemato Oncol, Tsukuba, Japan

来源：

LEUKEMIA | 2025年 / 39卷 / 05期

基金：

日本学术振兴会;

关键词：

CLONAL HEMATOPOIESIS; TET2; MUTATIONS; SURVIVAL; RHOA; ACTIVATION; EXPRESSION; PHASE-2; EVENT; CHOP;

D O I：

10.1038/s41375-025-02563-0

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Peripheral T-cell lymphoma (PTCL) exhibits a diverse clinical spectrum, necessitating methods to categorize patients based on genomic abnormalities or tumor microenvironment (TME) profiles. We conducted an integrative multiomics study in 129 PTCL patients, performing whole-exome sequencing and identifying three genetic subtypes: C1, C2, and C3. C2 was characterized by loss of tumor suppressor genes and chromosomal instability, while C1 and C3 shared T follicular helper (TFH)-related genomic alterations, with C3 also showing a high incidence of IDH2 mutations and chromosome 5 gain. Compared to C1, survival was significantly worse in C2 (HR 2.52; 95% CI, 1.37-4.63) and C3 (HR 2.14; 95% CI, 1.17-3.89). We also estimated the proportions of immune cell fractions from the bulk RNA sequencing data using CIBERSORTx and classified TME signatures into the following hierarchical clusters: TME1 (characterized by increased B and TFH cells), TME2 (macrophages), and TME3 (activated mast cells). TME2 was associated with shorter survival (HR 3.4; 95% CI, 1.6-7.5) and was more frequent in C2 (64.3%) than in C1 (7.7%), whereas C1 had more TME3 signatures (80.8% vs. 28.6%). These findings highlight a significant relationship between genetic subtypes and TME signatures in PTCL, with important implications for clinical prognosis.

引用

页码：1184 / 1195

页数：12

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