Comparison of biochemical and immunological profile of pediatric patients with acute myeloid leukemia in relation to healthy individuals

Sanches, Fabiane La Flor Ziegler; Nitsch, Taís M.; Vilela, M. M. S.; Sgarbieri, Valdemiro Carlos

doi:10.1016/j.jped.2014.12.004

Cited by 9 publications

(3 citation statements)

References 14 publications

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“…[44][45][46] This may explain the fact that PC2 and PC3 exhibit some peaks related to amino acids with higher intensities in the healthy compared to leukemic groups, especially Tyr and Trp. The peaks of proteins and glutathione (linked to erythrocytes) are also found in lower intensities in the leukemic group, which was also observed by Sanches et al, 47 who carried out a study comparing the biochemical profile between leukemic patients and healthy individuals. The peak assigned to the amino acid Phe was highlighted in the first three loadings.…”

Section: Exploratory Analysissupporting

confidence: 79%

Spectral model for diagnosis of acute leukemias in whole blood and plasma through Raman spectroscopy

et al. 2018

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Acute leukemias are oncohematological diseases that compromise the bone marrow and have a complex diagnostic definition, leading to a high mortality when diagnosed late. This study proposed to determine the spectral differences between whole blood and plasma samples of healthy and leukemic subjects based on Raman spectroscopy (RS), correlating these differences with their resulting biochemical alterations and performing discriminant analysis of the samples (n ¼ 38 whole blood and n ¼ 40 plasma samples). Raman spectra were obtained using a dispersive Raman spectrometer (830-nm wavelength, 280-mW laser power, 30-s exposure time) with a Raman probe. The exploratory analysis based on principal component analysis (PCA) of the blood and plasma sample's spectra showed loading vectors with peaks related to amino acids, proteins, carbohydrates, lipids, and carotenoids, being the spectral differences related to amino acids and proteins for whole blood samples, and mainly carotenoids for plasma samples. Discriminant models based on partial least squares (PLS) and PCA were developed and classified the spectra as healthy or leukemic, with sensitivity of 91.9% (PLS) and 83.9% (PCA), specificity of 100% (both PLS and PCA), and overall accuracy of 96.5% (PLS) and 93.0% (PCA) for the whole blood spectra. In plasma, the sensitivity was 95.7% (PLS) and 11.6% (PCA), specificity of 98% (PLS) and 100% (PCA), and overall accuracy of 97.1% (PLS) and 64.1% (PCA). The study demonstrated that RS is a technique with potential to be applied in the diagnosis of acute leukemias in whole blood samples.

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Section: Exploratory Analysissupporting

confidence: 79%

Spectral model for diagnosis of acute leukemias in whole blood and plasma through Raman spectroscopy

et al. 2018

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“…11 Recently, a study of a small pediatric AML cohort showed that IL-6 levels in peripheral blood were elevated compared with healthy age-matched controls. 12 However, the cytokine milieu in the BM niche of pediatric patients with AML has not been investigated previously. This is partially due to a lack of available banked samples.…”

Section: Introductionmentioning

confidence: 99%

Interleukin-6 levels predict event-free survival in pediatric AML and suggest a mechanism of chemotherapy resistance

Stevens¹,

Miller

Munoz³

et al. 2017

Blood Advances

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Key Points• IL-6 levels in bone marrow predict event-free survival in pediatric AML.• Exogenous IL-6 protects AML blasts from chemotherapy-induced apoptosis.The tumor microenvironment can protect cancer cells from conventional anticancer therapies. Thus, targeting these protective mechanisms could eradicate therapy-resistant cancer cells and improve outcomes. Interleukin-6 (IL-6) provides extrinsic protection for several solid tumors and multiple myeloma. In pediatric acute myeloid leukemia (AML), IL-6-induced STAT3 signaling frequently becomes stronger at relapse, and increases in IL-6-induced STAT3 activity are associated with inferior survival after relapse. These findings suggested that the IL-6-induced STAT3 pathway may promote chemotherapy resistance and disease progression. Thus, we investigated the dysregulation of IL-6 levels in the bone marrow niche in pediatric patients with AML and the association between IL-6 levels and outcome. We measured levels of over 40 cytokines and growth factors in plasma from diagnostic bone marrow aspirates of 45 pediatric AML patients and 7 healthy sibling controls. Of the measured cytokines, only IL-6 levels were associated with event-free survival. Importantly, the effect of elevated IL-6 was most striking among children classified as having a low risk of relapse. In these patients, 5-year event-free survival was 82.5% 6 11% for patients with low IL-6 levels at diagnosis (n 5 14) compared with 17.3% 6 11% for patients with elevated IL-6 (n 5 13, log-rank P 5 .0003). In vitro, exogenous IL-6 reduced mitoxantrone-induced apoptosis in cell lines and primary pediatric AML samples. These results suggest that IL-6 levels at diagnosis could be used to help identify children at high risk of relapse, particularly those who are otherwise classified as low risk by current algorithms.Moreover, the IL-6 pathway could represent a target for overcoming environment-mediated chemotherapy resistance.

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“…High serum levels of IL-6 have also been observed in these cancer conditions. In particular, compared to healthy children and adolescents, pediatric patients with acute myeloid leukemia showed higher concentrations of IL-6 and TNFα [ 29 ]. Up-regulation of cytokines in the bone microenvironment may contribute to peripheral and central components of cancer-induced bone pain, as osteoclasts are derived from monocyte/macrophage hematopoietic lineage and express receptors for TNFα and IL-6 [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

STOP Pain Project—Opioid Response in Pediatric Cancer Patients and Gene Polymorphisms of Cytokine Pathways

et al. 2022

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Moderate to severe cancer pain treatment in children is based on the use of weak and strong opioids. Pharmacogenetics play a central role in developing personalized pain therapies, as well as avoiding treatment failure and/or intolerable adverse drug reactions. This observational study aimed to investigate the association between IL-6, IL-8, and TNFα genetic single nucleotide polymorphisms (SNPs) and response to opioid therapy in a cohort of pediatric cancer patients. Pain intensity before treatment (PIt0) significantly differed according to IL-6 rs1800797 SNP, with a higher PI for A/G and G/G individuals (p = 0.017), who required a higher dose of opioids (p = 0.047). Moreover, compared to G/G subjects, heterozygous or homozygous individuals for the A allele of IL-6 rs1800797 SNP had a lower risk of having a PIt0 > 4. Dose24h and Dosetot were both higher in G/G individuals for TNFα rs1800629 (p = 0.010 and p = 0.031, respectively), while risk of having a PIt0 > 4 and a ∆VAS > 2 was higher for G/G subjects for IL-6 rs1800795 SNP compared to carriers of the C allele. No statistically significant association between genotypes and safety outcomes was found. Thus, IL-6 and TNFα SNPs could be potential markers of baseline pain intensity and opioid dose requirements in pediatric cancer patients.

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Comparison of biochemical and immunological profile of pediatric patients with acute myeloid leukemia in relation to healthy individuals

Abstract: It was possible to characterize the biochemical and immunological profile of pediatric patients with AML, as well as highlight some significant differences in these parameters when comparing with healthy children and adolescents.

Cited by 9 publications

References 14 publications

Spectral model for diagnosis of acute leukemias in whole blood and plasma through Raman spectroscopy

Spectral model for diagnosis of acute leukemias in whole blood and plasma through Raman spectroscopy

Interleukin-6 levels predict event-free survival in pediatric AML and suggest a mechanism of chemotherapy resistance

STOP Pain Project—Opioid Response in Pediatric Cancer Patients and Gene Polymorphisms of Cytokine Pathways

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