Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Oct;207(4):1357-1365.
doi: 10.1111/bjh.70059. Epub 2025 Jul 29.

Serum soluble interleukin-2 receptor levels in hairy cell leukaemia as a marker of tumour burden with prognostic value and as a tool for disease monitoring

Francesco Angotzi  1 , Alessandro Cellini  1 , Nicolò Danesin  1 , Simone Zoletto  1 , Andrea Serafin  1 , Chiara Adele Cavarretta  1 , Arianna Bevilacqua  1 , Laura Forlani  1 , Alessia Tonini  1 , Federica Frezzato  1 , Laura Bonaldi  2 , Marco Pizzi  3 , Diego Faggian  4 , Livio Trentin  1 , Andrea Visentin  1
Affiliations

Serum soluble interleukin-2 receptor levels in hairy cell leukaemia as a marker of tumour burden with prognostic value and as a tool for disease monitoring

Francesco Angotzi et al. Br J Haematol. 2025 Oct.

Abstract

Leukaemic cells from hairy cell leukaemia (HCL) secrete a soluble form of the interleukin-2 receptor (sIL-2R) which is measurable in serum. Previous evidence suggested that sIL-2R may correlate well with tumour burden and demonstrated a reduction in sIL-2R levels after therapy with recombinant interferon-α2. We evaluated the role of sIL-2R as a new prognostic factor and as a tool for disease monitoring. sIL-2R correlated well with other markers of neoplastic bulk and markedly decreased after treatment, with lower levels achieved in patients reaching complete remission (p = 0.002) or negative minimal residual disease (MRD, p = 0.034). Post-treatment levels ≤827 kU/L were strongly predictive of longer time to next treatment (TTNT) (median NR vs. 4.87 years; hazard ratio [HR]: 0.10; 95% confidence interval [CI]: 0.02-0.24; p < 0.001) and higher 5- and 10-year TTNT rates (5-year: 93% vs. 45%; 10-year: 83% vs. 11%). Furthermore, a ≥50% increase in sIL-2R levels over any 1-year interval during follow-up predicted impending relapse. In a context where patients with HCL are expected to achieve a life expectancy comparable to that of the general population, sIL-2R has the potential to serve as a non-invasive tool alongside MRD to predict relapse and to identify those patients who may fail to derive the most benefit from current treatments.

Keywords: hairy cell leukaemia; interleukins; purine analogues; residual disease.

PubMed Disclaimer

Conflict of interest statement

FA, AC, ND, SZ, CAC, LF, LB, FF; MP, AB, PF, AV and LT have no conflicts of interest to declare within this study.

Figures

FIGURE 1
FIGURE 1
Correlation of sIL‐2R levels with other markers of disease burden. (A, B) Boxplots showing correlation between median sIL‐2R levels and CD38 expression status (A) and with the presence/absence of splenomegaly (B); (C) correlation with spleen diameters; (D) correlation with the % of circulating hairy cells out of all WBCs; (E) correlation with beta‐2‐microglobulin levels; (F) correlation with the % of bone marrow infiltration; (G) correlation with WBC count; (H) correlation with LDH levels. LDH, lactate dehydrogenase; sIL‐2R, soluble form of the interleukin‐2 receptor; WBC, white blood cell count.
FIGURE 2
FIGURE 2
Boxplots comparing post‐therapy sIL‐2R levels according to response type (A) and MRD status (B). sIL‐2R, soluble form of the interleukin‐2 receptor.
FIGURE 3
FIGURE 3
Survival curves with predicted TTNT based on measured post‐therapy sIL‐2R levels at the time of response evaluation for the 827 kU/L cut‐off. In the whole cohort (A) and only in patients concomitantly achieving CR (B). CR, complete remission; sIL‐2R, soluble form of the interleukin‐2 receptor; TTNT, time to next treatment.
FIGURE 4
FIGURE 4
Survival curves showing predicted TTNT depending on the presence of a ≥50% increase in sIL‐2R levels during follow‐up (A) and predicted TTNT calculated from the time of the same increase in a landmark analysis (B). sIL‐2R, soluble form of the interleukin‐2 receptor; TTNT, time to next treatment. sIL‐2R, soluble form of the interleukin‐2 receptor; TTNT, time to next treatment.
See this image and copyright information in PMC

References

    1. Damoiseaux J. The IL‐2–IL‐2 receptor pathway in health and disease: the role of the soluble IL‐2 receptor. Clin Immunol. 2020;218:108515. - PubMed
    1. Brusko TM, Wasserfall CH, Hulme MA, Cabrera R, Schatz D, Atkinson MA. Influence of membrane CD25 stability on T lymphocyte activity: implications for immunoregulation. PLoS One. 2009;4(11):e7980. - PMC - PubMed
    1. Lindqvist CA, Christiansson LH, Simonsson B, Enblad G, Olsson‐Strömberg U, Loskog ASI. T regulatory cells control T‐cell proliferation partly by the release of soluble CD25 in patients with B‐cell malignancies. Immunology. 2010;131(3):371–376. - PMC - PubMed
    1. Chilosi M, Pizzolo G, Semenzato G, Cetto GL. Detection of a soluble form of the receptor for interleukin 2 in the serum of patients with hairy cell Leukaemia. Int J Biol Markers. 1986;1(2):101–104. - PubMed
    1. Chilosi M, Semenzato G, Cetto G, Ambrosetti A, Fiore‐Donati L, Perona G, et al. Soluble Interleukin‐2 receptors in the sera of patients with hairy cell leukemia: relationship with the effect of recombinant α‐interferon therapy on clinical parameters and natural killer in vitro activity. Blood. 1987;70(5):1530–1535. - PubMed

LinkOut - more resources