Associations between quality of life, fatigue, and cytokine levels in patients aged 50+ with acute myeloid leukemia

Panju, Abbas H.; Danesh, Ali; Minden, Mark D.; Kelvin, David J.; Alibhai, Shabbir M.H.

doi:10.1007/s00520-008-0512-3

Cited by 33 publications

(22 citation statements)

References 39 publications

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“…Decreased expression of IL-5, an important regulator of microglia and infiltrating macrophages in the brain [69], was also identified in tumor-bearing mice and tumor-free mice receiving radiotherapy alone. Associations with IL-5 and cancer-related fatigue have previously been described clinically [70]. Tumor-free mice receiving only radiotherapy also demonstrated decreased cortical expression of IL-6, which has been widely recognized as one of the most important regulators of neuroimmune function and has been repeatedly associated with cancer-related neurological dysfunction [15, 71–73].…”

Section: Discussionmentioning

confidence: 93%

Neuroinflammatory and cognitive consequences of combined radiation and immunotherapy in a novel preclinical model

et al. 2016

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BackgroundCancer patients often report behavioral and cognitive changes following cancer treatment. These effects can be seen in patients who have not yet received treatment or have received only peripheral (non-brain) irradiation. Novel treatments combining radiotherapy (RT) and immunotherapy (IT) demonstrate remarkable efficacy with respect to tumor outcomes by enhancing the proinflammatory environment in the tumor. However, a proinflammatory environment in the brain mediates cognitive impairments in other neurological disorders and may affect brain function in cancer patients receiving these novel treatments. Currently, gaps exist as to whether these treatments impact the brain in individuals with or without tumors and with regard to the underlying mechanisms.ResultsCombined treatment with precision RT and checkpoint inhibitor IT achieved control of tumor growth. However, BALB/c mice receiving combined treatment demonstrated changes in measures of anxiety levels, regardless of tumor status. C57BL/6J mice with tumors demonstrated increased anxiety, except following combined treatment. Object recognition memory was impaired in C57BL/6J mice without tumors following combined treatment. All mice with tumors showed impaired object recognition, except those treated with RT alone. Mice with tumors demonstrated impaired amygdala-dependent cued fear memory, while maintaining hippocampus-dependent context fear memory. These behavioral alterations and cognitive impairments were accompanied by increased microglial activation in mice receiving immunotherapy alone or combined with RT. Finally, based on tumor status, there were significant changes in proinflammatory cytokines (IFN-γ, IL-6, IL-5, IL-2, IL-10) and a growth factor (FGF-basic).Materials and MethodsHere we test the hypothesis that IT combined with peripheral RT have detrimental behavioral and cognitive effects as a result of an enhanced proinflammatory environment in the brain. BALB/c mice with or without injected hind flank CT26 colorectal carcinoma or C57BL/6J mice with or without Lewis Lung carcinoma were used for all experiments. Checkpoint inhibitor IT, using an anti-CTLA-4 antibody, and precision CT-guided peripheral RT alone and combined were used to closely model clinical treatment. We assessed behavioral and cognitive performance and investigated the immune environment using immunohistochemistry and multiplex assays to analyze proinflammatory mediators.ConclusionsAlthough combined treatment achieved tumor growth control, it affected the brain and induced changes in measures of anxiety, cognitive impairments, and neuroinflammation.

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Section: Discussionmentioning

confidence: 93%

Neuroinflammatory and cognitive consequences of combined radiation and immunotherapy in a novel preclinical model

et al. 2016

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“…Seven of these studies showed significant associations between fatigue and an immunogenomic marker. Eleven different fatigue measures were used in the 10 longitudinal studies, with one study using multiple fatigue scales (Panju et al, 2009) and another using an interview to measure fatigue (Olson et al, 2002). Three of these fatigue questionnaires were administered and validated in non-English languages (Ahlberg et al, 2004; Geinitz et al, 2001; Reinertsen et al, 2011).…”

Section: Resultsmentioning

confidence: 99%

A systematic review of the association between immunogenomic markers and cancer-related fatigue

Saligan

Kim

2012

Brain, Behavior, and Immunity

139

107

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Fatigue, which is one of the most commonly reported symptoms in cancer, can negatively impact the functional status and the health-related quality of life of individuals. This paper systematically reviews 34 studies to determine patterns of associations between immunogenomic markers and levels of cancer-related fatigue (CRF). Findings from the longitudinal studies revealed that elevated fatigue symptoms especially of women with early stages of breast cancer were associated with high levels of neutrophil/monocyte, IL-1ra, and IL-6 during radiation therapy; high levels of CD4+, IL-1β, and IL-6 with stressing stimuli; high levels of IL-1β during chemotherapy; low NK cell levels after chemotherapy; and presence of homozygous IL-6 and TNF alleles. In the cross-sectional studies, associations between levels of fatigue and immune/inflammatory markers were not consistently found, especially when covariates such as BMI, ethnicity, menopausal status, and educational level were controlled in the statistical analyses. However, a number of genomic markers were observed to be elevated mostly in fatigued breast cancer survivors in the cross-sectional studies. Gaps in knowledge and recommendations for future research are discussed.

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“…Increased production of cytokines such as TNFa, IL-6 and IL-10 by leukemic blasts and immune system cells has been reported in AML patients, but their role in pathogenesis of these patients is still not well understood [79]. IL-6 leads to activation of STAT3/5 transcription factors followed by increased expression of Twist1/2 proteins, because STAT3/5 is an upstream activator of Twist (Fig.…”

Section: Expression and Alternation Of Twist In Hematological Malignamentioning

confidence: 97%

Twist as a new prognostic marker in hematological malignancies

et al. 2015

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Twist proteins are members of basic helix-loop-helix family and are major regulators of embryogenesis. In adult humans, Twist proteins are mainly expressed in precursor cells, including myogenic, osteoblastic, chondroblastic and myelomonocytic lineages, maintaining their undifferentiated state. In addition, they play important roles in lymphocyte function and maturation. Recently, several studies have reported regulatory roles for Twist in the function and development of hematopoietic cells as well as in survival and development of numerous hematological malignancies. It is activated by numerous signal transduction pathways, including Akt, nuclear factor κB, Wnt, signal transducer and activator of transcription 3, mitogen-activated protein kinase and Ras signaling. Activated Twist has an anti-apoptotic role and protects cancer cells from apoptotic cell death. In addition, overexpression of Twist promotes the process of epithelial-mesenchymal transition, which has an essential role in cancer metastasis. Hereby, we review the aberrant expression of Twist in hematopoietic malignancies such as leukemias, lymphomas and myelodysplastic syndrome, which is related with poor prognosis and drug resistance in these disorders. Inactivation of Twist by small RNAs technology or chemotherapeutic inhibitors targeting Twist and upstream or downstream molecules of Twist signaling pathways may be helpful in management of disease to improve treatment strategies in malignancies.

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Associations between quality of life, fatigue, and cytokine levels in patients aged 50+ with acute myeloid leukemia

Abstract: These preliminary data provide support for a larger controlled study of cytokines, fatigue, and QOL in patients with AML.

Cited by 33 publications

References 39 publications

Neuroinflammatory and cognitive consequences of combined radiation and immunotherapy in a novel preclinical model

Neuroinflammatory and cognitive consequences of combined radiation and immunotherapy in a novel preclinical model

A systematic review of the association between immunogenomic markers and cancer-related fatigue

Twist as a new prognostic marker in hematological malignancies

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