Circulating HMGB1 is increased in myelodysplastic syndrome but not in other bone marrow failure syndromes: proof-of-concept cross-sectional study.

Autor:	Apodaca-Chávez E; Departamento de Hematología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico., Demichelis-Gómez R; Departamento de Hematología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico., Rosas-López A; Departamento de Hematología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico., Mejía-Domínguez NR; Departamento de Hematología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico., Galvan-López I; Departamento de Hematología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico., Addorosio M; Center for Biomedical Science, Feinstein Institutes for Medical Research, Manhasset, NY, USA., Tracey KJ; Center for Biomedical Science, Feinstein Institutes for Medical Research, Manhasset, NY, USA., Valdés-Ferrer SI; Departmento de Infectología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.; Departmento de Neurología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Tlalpan, 14080, Mexico City, Mexico.; Center for Biomedical Science, Feinstein Institutes for Medical Research, Manhasset, NY, USA.
Jazyk:	angličtina
Zdroj:	Therapeutic advances in hematology [Ther Adv Hematol] 2022 Oct 10; Vol. 13, pp. 20406207221125990. Date of Electronic Publication: 2022 Oct 10 (Print Publication: 2022).
DOI:	10.1177/20406207221125990
Abstrakt:	Background: Myelodysplastic syndrome (MDS) is associated with persistent immune activation. High mobility group box-1 (HMGB1) is a ubiquitous, functionally diverse, non-histone intranuclear protein. During acute and chronic inflammatory states, HMGB1 is actively released by inflammatory cells, further amplifying the inflammatory response. A role in MDS and other hypoplastic bone marrow (BM) disorders is incompletely understood. Objectives: The objective of the study is to evaluate whether circulating HMGB1 is elevated in patients with MDS and other BM failure syndromes [namely, aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH)]. Design: This is a observational, cross-sectional, single-center, exploratory study. Methods: We evaluated circulating concentrations of HMGB1, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in patients with MDS and age-matched hematologically healthy controls as well as patients with AA and PNH. Results: We included 66 patients with MDS and 65 age-matched controls as well as 44 patients with other BM failures (AA = 27, PNH = 17). Circulating levels of HMGB1 were higher in patients with MDS [median, 4.9 ng/ml; interquartile range (IQR): 2.3-8.1] than in AA (median, 2.6 ng/ml; IQR: 1.7-3.7), PNH (median, 1.7 ng/ml; IQR: 0.9-2.5), and age-matched healthy individuals (median, 1.9 ng/ml; IQR: 0.9-2.5) ( p  = 0.0001). We observed higher concentrations of HMGB1 in the very low/low-risk MDS patients than in the intermediate/high/very high-risk ones ( p  = 0.046). Finally, in comparison with patients with AA, those with hypocellular MDS (h-MDS) had significantly higher levels of circulating HMGB1 ( n  = 14; median concentration, 5.6 ng/ml, IQR: 2.8-7.3; p  = 0.006). We determined a circulating HMGB1 value of 4.095 ng/ml as a diagnostic cutoff differentiator between h-MDS and AA. Conclusion: These observations indicate that circulating HMGB1 is increased in patients with MDS. HMGB1 (but not IL-1β or TNF-α) differentiated between MDS and other BM failures, suggesting that HMGB1 may be mechanistically involved in MDS and a druggable target to decrease inflammation in MDS. Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. (© The Author(s), 2022.)
Databáze:	MEDLINE
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