Investigation of the Roles of Interleukin-15 in T-cell Acute Lymphoblastic Leukemia

Chenyang LI; Han ZHANG

Article Contents

Article Navigation > Journal of Kunming Medical University > 2026 > Uncorrected proof

Chenyang LI, Han ZHANG. Investigation of the Roles of Interleukin-15 in T-cell Acute Lymphoblastic Leukemia[J]. Journal of Kunming Medical University.

Citation:

Chenyang LI, Han ZHANG. Investigation of the Roles of Interleukin-15 in T-cell Acute Lymphoblastic Leukemia[J]. Journal of Kunming Medical University.

Chenyang LI, Han ZHANG. Investigation of the Roles of Interleukin-15 in T-cell Acute Lymphoblastic Leukemia[J]. Journal of Kunming Medical University.

Citation:

Chenyang LI, Han ZHANG. Investigation of the Roles of Interleukin-15 in T-cell Acute Lymphoblastic Leukemia[J]. Journal of Kunming Medical University.

PDF( 3581 KB)

Investigation of the Roles of Interleukin-15 in T-cell Acute Lymphoblastic Leukemia

Chenyang LI,
Han ZHANG^,

Institute of medical biology，Chinese Academy of Medical Science & Peking Union Medical College，Yunnan Kunming 650118，China

Received Date: 2026-01-20
Available Online: 2026-04-26

Abstract

Abstract

Objective To preliminarily investigate the molecular mechanisms of interleukin-15 （IL-15） in T-cell acute lymphoblastic leukemia （T-ALL）. Methods Open-access T-ALL datasets syn54032669 （n = 1335） and GSE33315 （n = 38） were used to analyze the correlation between IL-15 levels and clinical features including survival and minimal residual disease （MRD）; DESeq2 package in R was used to identify differentially expressed genes between IL-15-high and IL-15-low groups; packages including clusterProfiler were utilized to perform enrichment analyses; Annexin V/7-AAD staining and cell growth curves were performed to analyze the effects of IL-15 on the apoptosis and growth of T-ALL cells; real-time quantitative PCR and Western blot were performed to validate the effects of IL-15 on PI3K/AKT pathway and transcription of downstream genes. Results T-ALL patients with high IL-15 levels had longer overall survival （P < 0.05） and event-free survival （P = 0.074） but lower MRD levels （P < 0.0001）; IL-15 increased the proportion of early apoptotic cells but failed to inhibit the growth of T-ALL cells; IL-15 remarkably inhibited the transcription of neurotrophic receptor tyrosine kinase 1 （NTRK1）（P < 0.01） and fibroblast growth factor 9 （FGF9）（P < 0.05）, and also NTRK1-mediated activation of PI3K/AKT pathway; T-ALL patients with high NTRK1 and FGF9 levels had worse prognosis （P < 0.05）. Conclusion IL-15 exerts tumor suppressor-like functions by repressing the transcription of NTRK1 and FGF9, as well as inhibiting PI3K-AKT pathway activated by NTRK1 in T-ALL.
- T-cell acute lymphoblastic leukemia,
- Interleukin-15,
- PI3K/AKT pathway,
- Clinical prognosis

FullText(HTML)

References(42)

References

[1]	Pölönen P, Mullighan C G, Teachey D T. Classification and risk stratification in T-lineage acute lymphoblastic leukemia[J]. Blood, 2025, 145(14): 1464-1474. doi: 10.1182/blood.2023022920
[2]	李海金, 李慧园, 刘新妙, 等. 儿童高白细胞性急性淋巴细胞白血病的临床特征及预后分析[J]. 昆明医科大学学报, 2024, 45(7): 105-112. doi: 10.12259/j.issn.2095-610X.S20240716
[3]	Ruiz Pérez M, Vandenabeele P, Tougaard P. The thymus road to a T cell: migration, selection, and atrophy[J]. Front Immunol, 2024, 15: 1443910. doi: 10.3389/fimmu.2024.1443910
[4]	Huang J, Long Z, Jia R, et al. The Broad Immunomodulatory Effects of IL-7 and Its Application In Vaccines[J]. Front Immunol, 2021, 12: 680442. doi: 10.3389/fimmu.2021.680442
[5]	Chen D, Tang T X, Deng H, et al. Interleukin-7 Biology and Its Effects on Immune Cells: Mediator of Generation, Differentiation, Survival, and Homeostasis[J]. Front Immunol, 2021, 12: 747324. doi: 10.3389/fimmu.2021.747324
[6]	Wang C, Kong L, Kim S, et al. The Role of IL-7 and IL-7R in Cancer Pathophysiology and Immunotherapy[J]. Int J Mol Sci, 2022, 23(18): 10412. doi: 10.3390/ijms231810412
[7]	张雪绒, 苏永涛. CXC型趋化因子及其受体在糖尿病足溃疡中的表达及作用机制[J]. 河北医科大学学报, 2025, 46(5): 572-576. doi: 10.3969/j.issn.1007-3205.2025.05.013
[8]	Gower M, Li X, Aguilar-Navarro A G, et al. An inflammatory state defines a high-risk T-lineage acute lymphoblastic leukemia subgroup[J]. Sci Transl Med, 2025, 17(779): eadr2012. doi: 10.1126/scitranslmed.adr2012
[9]	Solati H, Zareinejad M, Ghavami A, et al. IL-35 and IL-18 Serum Levels in Children With Acute Lymphoblastic Leukemia: The Relationship With Prognostic Factors[J]. J Pediatr Hematol Oncol, 2020, 42(4): 281-286. doi: 10.1097/MPH.0000000000001667
[10]	Courtois L, Cabannes-Hamy A, Kim R, et al. IL-7 receptor expression is frequent in T-cell acute lymphoblastic leukemia and predicts sensitivity to JAK inhibition[J]. Blood, 2023, 142(2): 158-171. doi: 10.1097/01.hs9.0000968188.30640.78
[11]	Lenk L, Baccelli I, Laqua A, et al. The IL-7R antagonist lusvertikimab reduces leukemic burden in xenograft ALL via antibody-dependent cellular phagocytosis[J]. Blood, 2024, 143(26): 2735-2748. doi: 10.1182/blood.2023021088
[12]	Tremblay C S, Saw J, Boyle J A, et al. STAT5 activation promotes progression and chemotherapy resistance in early T-cell precursor acute lymphoblastic leukemia[J]. Blood, 2023, 142(3): 274-289. doi: 10.1016/j.exphem.2023.06.310
[13]	Lee H, Park S H, Shin E C. IL-15 in T-Cell Responses and Immunopathogenesis[J]. Immune Netw, 2024, 24(1): e11. doi: 10.4110/in.2024.24.e11
[14]	Ma S, Caligiuri M A, Yu J. Harnessing IL-15 signaling to potentiate NK cell-mediated cancer immunotherapy[J]. Trends Immunol, 2022, 43(10): 833-847. doi: 10.1016/j.it.2022.08.004
[15]	Tieu R, Zeng Q, Zhao D, et al. Tissue-resident memory T cell maintenance during antigen persistence requires both cognate antigen and interleukin-15[J]. Sci Immunol, 2023, 8(82): eadd8454. doi: 10.1126/sciimmunol.add8454
[16]	Apert C, Galindo-Albarrán A O, Castan S, et al. IL-2 and IL-15 drive intrathymic development of distinct periphery-seeding CD4⁺Foxp3⁺ regulatory T lymphocytes[J]. Front Immunol, 2022, 13: 965303. doi: 10.3389/fimmu.2022.965303
[17]	Sindaco P, Pandey H, Isabelle C, et al. The role of interleukin-15 in the development and treatment of hematological malignancies[J]. Front Immunol, 2023, 14: 1141208. doi: 10.3389/fimmu.2023.1141208
[18]	Nandi M, Ghosh A, Akbari S A, et al. IL-15 prevents the development of T-ALL from aberrant thymocytes with impaired DNA repair functions and increased NOTCH1 activation[J]. Cancers, 2023, 15(3): 671. doi: 10.3390/cancers15030671
[19]	Stajer M, Horacek J M, Kupsa T, et al. The role of chemokines and interleukins in acute lymphoblastic leukemia: a systematic review[J]. J Appl Biomed, 2024, 22(4): 165-184. doi: 10.32725/jab.2024.024
[20]	Wang T, Chen B, Meng T, et al. Identification and immunoprofiling of key prognostic genes in the tumor microenvironment of hepatocellular carcinoma[J]. Bioengineered, 2021, 12(1): 1555-1575. doi: 10.1080/21655979.2021.1918538
[21]	Costea J, Rauwolf K K, Zafferani P, et al. Role of stem-like cells in chemotherapy resistance and relapse in pediatric T-cell acute lymphoblastic leukemia[J]. Nat Commun, 2025, 16(1): 5413. doi: 10.1038/s41467-025-61222-1
[22]	Park J E, Botting R A, Domínguez Conde C, et al. A cell atlas of human thymic development defines T cell repertoire formation[J]. Science, 2020, 367(6480): eaay3224. doi: 10.1126/science.aay3224
[23]	刘琴, 杨坤, 牛振鹏, 等. 异藤黄酚对急性淋巴细胞白血病Jurkat细胞增殖和凋亡的影响及机制[J]. 贵州医科大学学报, 2023, 48(11): 1273-1281+1291.
[24]	Thielemans N, Demeyer S, Mentens N, et al. TAL1 cooperates with PI3K/AKT pathway activation in T-cell acute lymphoblastic leukemia[J]. Haematologica, 2022, 107(10): 2304-2317. doi: 10.3324/haematol.2021.279718
[25]	Chen C, Xu J, Sussman J H, et al. Single-cell panleukemia signatures of HSPC-like blasts predict drug response and clinical outcome[J]. Blood, 2025, 145(23): 2685-2700. doi: 10.1182/blood.2024027270
[26]	Liu Y, Du Z, Li L, et al. scRNA-seq reveals an immune microenvironment and JUN-mediated NK cell exhaustion in relapsed T-ALL[J]. Cell Rep Med, 2025, 6(5): 102098. doi: 10.1016/j.xcrm.2025.102098
[27]	Cui M, Ding X, Jiang Y, et al. PDGFC secreted by cancer-associated fibroblasts promotes epithelial-mesenchymal transition and immunosuppression in lung adenocarcinoma[J]. Acta Biochim Biophys Sin, 2025, 57(10): 1625-1635. doi: 10.3724/abbs.2025042
[28]	Akiyama T, Yasuda T, Uchihara T, et al. Stromal Reprogramming through Dual PDGFRα/β Blockade Boosts the Efficacy of Anti-PD-1 Immunotherapy in Fibrotic Tumors[J]. Cancer Res, 2023, 83(5): 753-770. doi: 10.1158/0008-5472.CAN-22-1890
[29]	De Coninck S, De Smedt R, Lintermans B, et al. Targeting hyperactive platelet-derived growth factor receptor-β signaling in T-cell acute lymphoblastic leukemia and lymphoma[J]. Haematologica, 2024, 109(5): 1373-1384. doi: 10.1016/j.exphem.2022.07.122
[30]	Paolino J, Dimitrov B, Apsel Winger B, et al. Integration of genomic sequencing drives therapeutic targeting of PDGFRA in T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma[J]. Clin Cancer Res, 2023, 29(22): 4613-4626. doi: 10.1158/1078-0432.CCR-22-2562
[31]	Jiang T, Wang G, Liu Y, et al. Development of small-molecule tropomyosin receptor kinase (TRK) inhibitors for NTRK fusion cancers[J]. Acta Pharm Sin B, 2021, 11(2): 355-372. doi: 10.1016/j.apsb.2020.05.004
[32]	Jiang J, Bai J, Qin T, et al. NGF from pancreatic stellate cells induces pancreatic cancer proliferation and invasion by PI3K/AKT/GSK signal pathway[J]. J Cell Mol Med, 2020, 24(10): 5901-5910. doi: 10.1111/jcmm.15265
[33]	Li H, Wei H, Zhen T, et al. Novel NOTCH2-NTRK1 fusion confers osimertinib resistance in EGFR-mutant non-small cell lung cancer by interacting with EGFR[J]. Transl Oncol, 2026, 63: 102577. doi: 10.1016/j.tranon.2025.102577
[34]	Fan Y, Zhang B, Du X, et al. Regulating Tumorigenicity and Cancer Metastasis through TRKA Signaling[J]. Curr Cancer Drug Targets, 2024, 24(3): 271-287. doi: 10.2174/1568009623666230904150957
[35]	Kyriakidis I, Mantadakis E, Stiakaki E, et al. Infectious Complications of Targeted Therapies in Children with Leukemias and Lymphomas[J]. Cancers, 2022, 14(20): 5022. doi: 10.3390/cancers14205022
[36]	Quinlan L, Page E C, Rehn J, et al. High expression of NTRK1 in ETV6: : RUNX1 positive acute lymphoblastic leukaemia drives factor independence and sensitivity to larotrectinib[J]. Pediatr Blood Cancer, 2025, 72(11): e31983. doi: 10.1002/pbc.31983
[37]	Chen M, Liang H, Wu M, et al. Fgf9 regulates bone marrow mesenchymal stem cell fate and bone-fat balance in osteoporosis by PI3K/AKT/Hippo and MEK/ERK signaling[J]. Int J Biol Sci, 2024, 20(9): 3461-3479. doi: 10.7150/ijbs.94863
[38]	Yin H, Staples S C R, Pickering J G. The fundamentals of fibroblast growth factor 9[J]. Differentiation, 2024, 139: 100731. doi: 10.1016/j.diff.2023.09.004
[39]	Ishioka K, Yasuda H, Hamamoto J, et al. Upregulation of FGF9 in Lung Adenocarcinoma Transdifferentiation to Small Cell Lung Cancer[J]. Cancer Res, 2021, 81(14): 3916-3929. doi: 10.1158/0008-5472.CAN-20-4048
[40]	Zhang B, Liu Y, Yu J, et al. Upregulation of FGF9 and NOVA1 in cancer-associated fibroblasts promotes cell proliferation, invasion and migration of triple negative breast cancer[J]. Drug Dev Res, 2024, 85(3): e22185. doi: 10.1002/ddr.22185
[41]	Zhang L, Zhang Q, Teng D, et al. FGF9 recruits β-catenin to increase hepatic ECM synthesis and promote NASH-driven HCC[J]. Adv Sci, 2023, 10(28): 2301166. doi: 10.1002/advs.202301166
[42]	Dawidowska M, Maćkowska-Maślak N, Drobna-Śledzińska M, et al. Small RNA-seq reveals similar miRNA transcriptome in children and young adults with T-ALL and indicates miR-143-3p as novel candidate tumor suppressor in this leukemia[J]. Int J Mol Sci, 2022, 23(17): 10117. doi: 10.3390/ijms231710117

Relative Articles(20)

Relative Articles

[1]	Ningxin ZHANG, Li LI, Shan LIU, Jianyun NIE. Advances in Squalene Epoxidase as A Potential Therapeutic Target in Breast Cancer. Journal of Kunming Medical University, doi: 10.12259/j.issn.2095-610X.S20260401
[2]	Yaru SUN, Guangli SHENG, Xuan ZHANG. Research Progress of PI3K Signaling Pathway Inhibitors in the Treatment of Pulmonary Fibrosis. Journal of Kunming Medical University, doi: 10.12259/j.issn.2095-610X.S20250620
[3]	Haixing ZHANG, Jingyun ZHANG, Dandan XU, Lu CAO, Jingjing LI. The Mechanism of miR-23 Regulating PI3K/AKT/mTOR Pathway to Improve Myocardial Angiogenesis in Hypertensive Heart Failure Rats. Journal of Kunming Medical University, doi: 10.12259/j.issn.2095-610X.S20251105
[4]	Zhixiao LI, Xia ZHENG, Chunling LI, Qingsheng LIU, Heng ZHANG. The Molecular Mechanism of miR-205-5p Targeting ERBB3 to Regulate PI3K/AKT/mTOR Pathway and Inhibit Angiogenesis in Hemorrhoids. Journal of Kunming Medical University, doi: 10.12259/j.issn.2095-610X.S20240604
[5]	Chunyan LIU, Bingqing CHANG, Chao LI, Xin REN, Xiaoqin LIU. The Relationship between T Lymphocyte Subsets and Pathological Characteristics of Acute Myeloid Leukemia and the Value of Predicting Chemotherapy Prognosis. Journal of Kunming Medical University, doi: 10.12259/j.issn.2095-610X.S20240518
[6]	Qi NIE, Li LIU, Yue TIAN, Xiaoyan MAO, Qulian GUO, Xin TIAN. Abnormal Clinical Features and Prognosis of ACTH in Pediatric Acute B Lymphocytic Leukemia. Journal of Kunming Medical University, doi: 10.12259/j.issn.2095-610X.S20241012
[7]	Haijin LI, Huiyuan LI, Xinmiao LIU, Yue TIAN, Na LI, Zhengcheng DUAN, Xin TIAN. Clinical Features and Prognosiss of Pediatric Acute Lymphoblastic Leukemia with Hyperleukocytosis. Journal of Kunming Medical University, doi: 10.12259/j.issn.2095-610X.S20240716
[8]	Ying LIU, Shujie SONG, Lin WU. Clinical and Pathological Characteristics of Extrapleural Solitary Fibrous Tumor. Journal of Kunming Medical University, doi: 10.12259/j.issn.2095-610X.S20240117
[9]	Shulan SHI, Lijuan QIU, Liyue KUI, Min SU, Bailing ZHOU, Rongjie LI, Jianming SUN. Diagnostic Value of Interleukin-6，Interleukin-10，High-sensitivity C-reactive Protein and Procalcitonin in Children with Acute Lymphoblastic Leukemia Complicated by Infection. Journal of Kunming Medical University, doi: 10.12259/j.issn.2095-610X.S20230115
[10]	Weimin LIU, Yiqun MA, Zhuo TIAN, Yang TANG. Regulatory Role of PI3K/Akt Signaling Pathway in Hypertrophic Scar. Journal of Kunming Medical University, doi: 10.12259/j.issn.2095-610X.S20230313
[11]	Zhu Li Ping , Sun Jing . . Journal of Kunming Medical University,
[12]	Sun Jian Ming , He Xi Jun , Li Chang Feng , Li Hui Ying , Li Ren Qiu , Pu Ming , Su Qin . . Journal of Kunming Medical University,
[13]	Sun Jian Ming , Dong Fang . Adverse Reactions in Children with Acute Lymphoblastic Leukemia after Chemotherapy. Journal of Kunming Medical University,
[14]	Wang Ya Nan , Li Zhi Gang , Zhang Chao , Li Shu De , Li Tao , Peng Jian Zhi . Homocysteine Suppress PI3K/Akt Signaling Pathway via Promoting the Expression of TRB3 in Adipose Tissue. Journal of Kunming Medical University,
[15]	Lv Chao Shao . Impact on the Expression of CD123 on K562 Cells Induced by rhIFN-γ. Journal of Kunming Medical University,
[16]	Shen Xiu Fen , Xue Li , Fan Shou Rui , He Xiao Juan , Wang Xue Jiao , Yu Jing Xing , Xia Mei Hua , Yin Lie Fen . Application of Serum VEGF-C,VEGFR-2 and VEGFR-3 Expression Level in Monitoring Curative Effects and Prognosis of Acute Leukemia. Journal of Kunming Medical University,
[17]	Gu Fang Na . . Journal of Kunming Medical University,
[18]	Sun Jian Ming . . Journal of Kunming Medical University,
[19]	. . Journal of Kunming Medical University,
[20]	Yao Jin . . Journal of Kunming Medical University,