Open Access
ARTICLE
P2RX1 Influences the Prognosis of Ph+/Ph-Like ALL through Energy and Calcium Metabolism
Xiangmei Ye1,2,3, Baoyi Yang4, Xin Zhang5, Luyuan Yang1, Likun Zhang5, Qin Ren1, Xiaobing Li1, Leiguang Feng1, Lanlan Wei3,6,7,*, Peng Song1, Yuqing Ye8, Xin Lian9, Yujuan Gao9, Haidi Tang1, Zhiyu Liu1
1 Department of Laboratory Diagnostics, The First Affiliated Hospital of Harbin Medical University, Harbin, 150000, China
2 Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, 150000, China
3 Department of Pathogenic Microbiology, Harbin Medical University, Harbin, 150000, China
4 Third Department of Surgery, The First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin, 150000, China
5 Central Laboratory, The First Affiliated Hospital of Harbin Medical University, Harbin, 150000, China
6 National Clinical Research Center for Infectious Diseases, The Third People’s Hospital of Shenzhen, Shenzhen, 518000, China
7 The Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, 518000, China
8 Guangzhou Xuekang Lu Daopei Biotechnology, Guangzhou, 510000, China
9 Department of Hematology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150000, China
* Corresponding Author: Lanlan Wei. Email: 
(This article belongs to the Special Issue: The Metabolic Reprogramming and Its Intervention in Tumorigenesis)
Oncology Research https://doi.org/10.32604/or.2025.068814
Received 06 June 2025; Accepted 11 October 2025; Published online 14 November 2025
Abstract
Objectives: Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia and Philadelphia-like B-cell acute lymphoblastic leukemia (Ph+/Ph-like ALL) constitute the majority of relapsed/refractory B-ALL (R/R B-ALL) cases, highlighting an urgent need to discover new therapeutic targets. This study aims to elucidate the mechanisms underlying poor prognosis in Ph+/Ph-like ALL through transcriptome sequencing and functional cytological assays, with the goal of informing new clinical treatment strategies. Results: Transcriptomic analysis of Ph+/Ph-like ALL patients revealed that low expression of P2X Purinoceptor 1 (P2RX1) was associated with unfavorable outcomes. Specifically, patients with poor prognosis and low P2RX1 expression exhibited downregulation of genes involved in energy and calcium metabolism pathways, along with upregulation of genes governing key cellular processes such as cell proliferation (e.g., MYC), cell cycle progression (e.g., CCND2), and apoptosis inhibition (e.g., DASP6). Cellular experiments demonstrated that SUP-B15 cells overexpressing P2RX1 displayed elevated intracellular levels of ATP, calcium, and glucose, together with enhanced glycolytic capacity, compared to empty vector controls. Treatment of SUP-B15 cells with dexamethasone (Dex), Imatinib, or their combination significantly suppressed proliferation and promoted apoptosis, which was accompanied by increases in intracellular ATP, calcium, and glucose. Moreover, exogenous ATP administration (a P2RX1 agonist) enhanced apoptosis and inhibited proliferation in control cells. Conversely, treatment with NF449 (a P2RX1 inhibitor) increased proliferation in both P2RX1-overexpressing and control SUP-B15 cells. Conclusion: Our findings indicate that P2RX1 may exert this function through modulating energy metabolism and calcium homeostasis, resulting in elevated intracellular calcium levels. Sustained elevation of calcium promotes apoptosis, whereas exogenous ATP activates P2RX1, enhances calcium influx, and attenuates the suppression of apoptosis associated with P2RX1 underexpression, ultimately correlating with improved treatment response.
Keywords
Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL); Philadelphia chromosome-like B-cell acute lymphoblastic leukemia (Ph-like ALL); transcriptome sequencing; P2X purinoceptor 1
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