Elevated plasma levels of IL-6 and MCP-1 selectively identify CML patients who better sustain molecular remission after TKI withdrawal

Pavlovsky, Carolina; Cordoba, Bianca Vasconcelos; Sánchez, María Belén; Moiraghi, Beatriz; Varela, Ana Inés; Custidiano, Rosario; Fernández, Isolda; Freitas, María Josefina; Ventriglia, Maria Verónica; Bendek, Georgina; Mariano, Romina; Osorio, María José Mela; Pavlovsky, Miguel Angel; Labanca, Ana García de; Foncuberta, Cecilia; Giere, Isabel; Vera, Masiel; Juni, Mariana; Mordoh, José; Ávalos, Julio César Sánchez; Cueto, Gerardo Rubén; Miranda, Sílvia Helena Galvão de; Levy, Estrella Mariel; Bianchini, Michele

doi:10.1186/s13045-023-01440-6

Cited by 5 publications

(4 citation statements)

References 11 publications

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“…The severity of infection can be partially identified by the expression level of IL-6 according to earlier research [36]. However, while the results from the present study align with the majority of studies confirming the detrimental signaling promoted by elevated levels of IL-6, another study demonstrated that low levels of IL-6 are associated with an 8-fold higher risk of relapse in patients in treatment-free remission (TFR) of CML [37].…”

Section: Discussionsupporting

confidence: 82%

Vitamin C Inhibits Lipopolysaccharide-Induced Hyperinflammatory State of Chronic Myeloid Leukemia Cells through Purinergic Signaling and Autophagy

Pires,

Brandão-Rangel,

Silva-Reis

et al. 2024

Nutrients

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Background: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the overproduction of white blood cells, leading to symptoms such as fatigue, infections, and other complications. CML patients must take measures to prevent infections to mitigate the exacerbation of cancer cell proliferation and comorbidities. Methods: This study investigated whether vitamin C can suppress the hyperinflammatory activation of K-562 cells induced by lipopolysaccharide (LPS) and whether purinergic signaling (ATP and P2X7 receptor) and autophagy play a role in it. Two different doses of vitamin C (5 µg/mL and 10 µg/mL) were employed, along with the lysosome inhibitor chloroquine (CQ; 100 µM), administered 2 h prior to LPS stimulation (10 ng/mL) for a duration of 22 h in K-562 cells (3 × 105 cells/mL/well). Results: Both doses of vitamin C reduced the release of interleukin-6 (IL-6) (5 µg/mL, p < 0.01 and 10 µg/mL, p < 0.01) and tumor necrosis factor (TNF) (5 µg/mL, p < 0.01 and 10 µg/mL, p < 0.01) induced by LPS. Furthermore, in LPS + CQ-stimulated cells, vitamin C at a concentration of 10 µg/mL inhibited the expression of LC3-II (p < 0.05). Conversely, both doses of vitamin C led to the release of the anti-inflammatory cytokine interleukin-10 (IL-10) (5 µg/mL, p < 0.01 and 10 µg/mL, p < 0.01), while only the 10 µg/mL dose of vitamin C induced the release of Klotho (10 µg/mL, p < 0.01). In addition, both doses of vitamin C reduced the accumulation of ATP (5 µg/mL, p < 0.01 and 10 µg/mL, p < 0.01) and decreased the expression of the P2X7 receptor at the mRNA level. Conclusions: Vitamin C inhibits the hyperinflammatory state induced by LPS in K-562 cells, primarily by inhibiting the ATP accumulation, P2X7 receptor expression, and autophagy signaling.

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Section: Discussionsupporting

confidence: 82%

Vitamin C Inhibits Lipopolysaccharide-Induced Hyperinflammatory State of Chronic Myeloid Leukemia Cells through Purinergic Signaling and Autophagy

Pires,

Brandão-Rangel,

Silva-Reis

et al. 2024

Nutrients

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“…For these patients, baseline characteristics and treatment information are shown in Figure 1C . Regarding clinical variables, only prior time in deep molecular response (DMR) and treatment duration were significantly associated with the probability of successful TFR in our cohort, as we have recently published ( 12 ). Since NK cell receptors play a key role in target recognition and transmission of activating or inhibitory signals after binding to their ligands, we thus decided to examine the expression of a large panel of NK cell receptors, both at the time of discontinuation as well as at specific subsequent time points (3 and 12 months).…”

Section: Resultssupporting

confidence: 54%

“…The study was conducted as a sub-study of the Argentina Stop Trial (AST) registered in the National Registry of Health Research (RENIS: ISO02688) ( 12 ). For this prospective, single-arm, open-label, nonrandomized trial, we enrolled 46 patients with CP-CML at 7 Argentinean centers in Buenos Aires city and 3 more provinces (Buenos Aires province, Mendoza and Entre Rios).…”

Section: Methodsmentioning

confidence: 99%

“…Argentine Stop Trial (AST) is to date the largest clinical trial of patients in Latin America who stopped across all types of TKIs. In this ongoing multicenter trial, we demonstrated the feasibility of TFR in our country and we described several novel potential biomarkers useful to improve patients’ selection for discontinuation ( 12 ).…”

Section: Introductionmentioning

confidence: 99%

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In-depth characterization of NK cell markers from CML patients who discontinued tyrosine kinase inhibitor therapy

Sanchez,

Vasconcelos Cordoba,

Pavlovsky

et al. 2023

Front. Immunol.

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IntroductionTreatment-free remission (TFR) in patients with chronic myeloid leukemia in chronic phase is considered a safe option if suitable molecular monitoring is available. However, the question arises as to which factors can contribute to the maintenance of TFR, and immunologic surveillance of the remaining leukemic cells is believed to be one of them. Argentina Stop Trial is an open-label, single-arm, multicenter trial assessing TFR after tyrosine kinase inhibitors interruption, that after more than 4 years showed a successful TFR rate of 63%.MethodsIn this context, we set up an immunological study by flow cytometry in order to analyze specific NK cell subsets from peripheral blood patient samples both at the time of discontinuation as well as during the subsequent months.ResultsAt the time of discontinuation, patients show a mature NK cell phenotype, probably associated to TKI treatment. However, 3 months after discontinuation, significant changes in several NK cell receptors occurred. Patients with a higher proportion of CD56dim NK and PD-1+ NK cells showed better chances of survival. More interestingly, non-relapsing patients also presented a subpopulation of NK cells with features associated with the expansion after cytomegalovirus infection (expression of CD57+NKG2C+), and higher proportion of NKp30 and NKp46 natural cytotoxicity receptors, which resulted in greater degranulation and associated with better survival (p<0.0001).DiscussionThis NK cell subset could have a protective role in patients who do not relapse, thus further characterization could be useful for patients in sustained deep molecular response.

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Investigating the potential risk of cadmium exposure on seizure severity and anxiety-like behaviors through the ferroptosis pathway in epileptic mice: An integrated multi-omics approach

Chang,

Jiang,

Dou

et al. 2024

Journal of Hazardous Materials

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Elevated plasma levels of IL-6 and MCP-1 selectively identify CML patients who better sustain molecular remission after TKI withdrawal

Cited by 5 publications

References 11 publications

Vitamin C Inhibits Lipopolysaccharide-Induced Hyperinflammatory State of Chronic Myeloid Leukemia Cells through Purinergic Signaling and Autophagy

Vitamin C Inhibits Lipopolysaccharide-Induced Hyperinflammatory State of Chronic Myeloid Leukemia Cells through Purinergic Signaling and Autophagy

In-depth characterization of NK cell markers from CML patients who discontinued tyrosine kinase inhibitor therapy

Investigating the potential risk of cadmium exposure on seizure severity and anxiety-like behaviors through the ferroptosis pathway in epileptic mice: An integrated multi-omics approach

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