DARS expression in BCR/ABL1-negative myeloproliferative neoplasms and its association with the immune microenvironment

Q: What was the primary goal of this study in BCR/ABL1-negative MPNs?

To determine DARS expression in patients with MPNs and to evaluate how DARS relates to circulating immune cell profiles and cytokines.

Q: How was DARS expression measured across MPN subtypes?

DARS expression in MPN subtypes (PV, ET, and PMF) was assessed at the protein level using immunohistochemical analysis.

Q: What immune-related associations were observed with DARS expression?

Higher DARS expression was linked to lower CD4+ T cells and a reduced CD4+/CD8+ ratio, as well as changes in CD68+ tumor-associated macrophages, while showing positive correlations with IL-2, IL-5, IL-6, and IFN-γ.

Sep 21, 2026

Uploaded by Noah

Aspartyl-tRNA synthetase (DARS) expression and its immune associations were investigated in BCR/ABL1-negative myeloproliferative neoplasms (MPNs). DARS protein levels were assessed by immunohistochemistry across PV, ET, and PMF subtypes, and circulating immune cells and cytokines were profiled by flow cytometry. DARS was significantly overexpressed in all MPN subtypes versus controls, with higher expression linked to splenomegaly. DARS correlated negatively with CD4+ T cells and the CD4+/CD8+ ratio, and with CD68+ tumor-associated macrophages, but positively with IL-2, IL-5, IL-6, and IFN-γ.

LanguageEnglish

CategoryResearch & Report

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Pages11

Reading Time28 min

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DARS expression in BCR/ABL1-negative MPNs

Immune cell and cytokine profiling

Clinical and immunological correlations

Background on MPNs and immune involvement

Current treatment challenges and unmet needs

Metabolic reprogramming and immune metabolism

DARS as an aminoacyl-tRNA synthetase in cancer

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN DARS expression in BCR/ ABL1‑negative myeloproliferative neoplasms and its association with the immune microenvironment Hao Xiong1,3, Minjing Liao4, Huitao Zhang2, Yanhong Li1, Jun Bai1, Jinping Zhang1, Lijuan Li1* & Liansheng Zhang1* DARS, encoding for aspartyl‑tRNA synthetase, is implicated in the pathogenesis of various cancers, including renal cell carcinoma, glioblastoma, colon cancer, and gastric cancer. Its role in BCR/ ABL1‑negative myeloproliferative neoplasms (MPNs), however, remains unexplored. This study aimed to elucidate the expression of DARS in patients with MPNs (PV 23, ET 19, PMF 16) through immunohistochemical analysis and to examine the profiles of circulating immune cells and cytokines using flow cytometry. Our findings indicate a significant overexpression of DARS in all MPNs subtypes at the protein level compared to controls (P < 0.05) . Notably, elevated DARS expression was linked to splenomegaly in MPNs patients. The expression of DARS showed a negative correlation with CD4+ T cells (R = − 0.451, P = 0.0004) and CD4+ T/CD8+ T cell ratio (R = − 0.3758, P = 0.0040), as well as with CD68+ tumor‑associated macrophages (R = 0.4037, P = 0.0017). Conversely, it was positively correlated with IL-2 (R = 0.5419, P < 0.001), IL-5 (R = 0.3161, P = 0.0166), IL-6 (R = 0.2992, P = 0.0238), and IFN-γ (R = 0.3873, P = 0.0029). These findings underscore a significant association between DARS expression in MPNs patients and specific clinical characteristics, as well as immune cell composition. Further investigation into the interplay between DARS and the immune microenvironment in MPNs could shed light on the underlying mechanisms of MPNs pathogenesis and immune dysregulation. Keywords Myeloproliferative neoplasms, Immune microenvironment, Immune metabolism, DARS The BCR/ABL1-negative myeloproliferative neoplasms (MPNs) are a group of clonal diseases that affect the hematopoietic stem and progenitor cells (HSPC) and are characterized by the abnormal proliferation of one or more myeloid cell lines1. Essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF) are common subtypes of MPNs. They all are acquired stem cell neoplasms that arise due to somatic“driver” mutations, including the JAK2V617F, CALR, and MPL mutations. Additional mutations are often determinants for myelofibrotic and leukemic transformation2. All these conditions, especially PMF, may progress toward a fibrotic involution of BM, frequently accompanied by cytopenia and splenomegaly and shorter overall survival (OS)3. To improve the quality of life and survival of MPNs patients, the current clinical focus is on reducing the thrombotic risk, relieving the symptom burden, improving the prognosis, and reducing transfusion requirements4. Conventional interventions and surgical treatments include phlebotomy, radiotherapy, splenectomy, and allogeneic hematopoietic stem cell transplantation5. However, these treatments are prone to complications such as hypovolemia, hypocalcemia, bleeding, and infection6,7. Allogeneic hematopoietic stem cell transplantation has the potential to cure MPNs but is associated with a high risk of developing graft-versus-host disease (GVHD) and postoperative mortality8. Current conventional drugs for the treatment of MPNs include hydroxyurea, interferon alpha, androgens, alkylating agents, immunomodulators, and anticoagulants9. However, 1Department of Hematology, The Second Hospital of Lanzhou University, Lanzhou, China. 2Department of General Practice, The Affiliated Hospital of Southwest Medical University, Luzhou, China. 3Stem Cell Immunity and Regeneration Key Laboratory of Luzhou, The Affiliated Hospital, Southwest Medical University, Luzhou, China. 4Second Clinical Medical College, Lanzhou University, Lanzhou, China. * email: [doctorjuan@sina.com](doctorjuan@sina.com); [doctorzhanglsh@sina.com](doctorzhanglsh@sin

FAQs

What was the primary goal of this study in BCR/ABL1-negative MPNs?

To determine DARS expression in patients with MPNs and to evaluate how DARS relates to circulating immune cell profiles and cytokines.

How was DARS expression measured across MPN subtypes?

DARS expression in MPN subtypes (PV, ET, and PMF) was assessed at the protein level using immunohistochemical analysis.

What immune-related associations were observed with DARS expression?

Higher DARS expression was linked to lower CD4+ T cells and a reduced CD4+/CD8+ ratio, as well as changes in CD68+ tumor-associated macrophages, while showing positive correlations with IL-2, IL-5, IL-6, and IFN-γ.

Sep 21, 2026

Uploaded by Noah