Cerebrospinal Fluid IL-6, TNF-α and MCP-1 in Children with Acute Lymphoblastic Leukaemia during Chemotherapy

Protas, Piotr; Hołownia, Adam; Muszyńska-Rosłan, Katarzyna; Wielgat, Przemysław; Krawczuk‐Rybak, Maryna; Braszko, Jan J.

doi:10.1055/s-0031-1295477

Cited by 10 publications

(16 citation statements)

References 7 publications

(10 reference statements)

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“…We next sought to understand which signalling pathways might be mediating the protective effect of CSF. We hypothesized that either the re‐activation of ERK/MAP kinase signalling or PI‐3 kinase signalling may be important; the latter can be activated by factors in CSF such as IGF‐1 and IL‐6 (Bilic et al., ; Protas et al., ). To test the functional significance of these pathways, we combined PLX4720 treatment with either a MEK inhibitor, PD184352 or a pan PI‐3 kinase inhibitor, LY294002.…”

Section: Resultsmentioning

confidence: 99%

Extrinsic factors can mediate resistance to BRAF inhibition in central nervous system melanoma metastases

Seifert¹,

Hirata

Gore³

et al. 2015

Pigment Cell Melanoma Res

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SummaryHere, we retrospectively review imaging of 68 consecutive unselected patients with BRAF V600‐mutant metastatic melanoma for organ‐specific response and progression on vemurafenib. Complete or partial responses were less often seen in the central nervous system (CNS) (36%) and bone (16%) compared to lung (89%), subcutaneous (83%), spleen (71%), liver (85%) and lymph nodes/soft tissue (83%), P < 0.001. CNS was also the most common site of progression.Based on this, we tested in vitro the efficacy of the BRAF inhibitors PLX4720 and dabrafenib in the presence of cerebrospinal fluid (CSF). Exogenous CSF dramatically reduced cell death in response to both BRAF inhibitors. Effective cell killing was restored by co‐administration of a PI‐3 kinase inhibitor.We conclude that the efficacy of vemurafenib is variable in different organs with CNS being particularly prone to resistance. Extrinsic factors, such as ERK‐ and PI3K‐activating factors in CSF, may mediate BRAF inhibitor resistance in the CNS.

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Section: Resultsmentioning

confidence: 99%

Extrinsic factors can mediate resistance to BRAF inhibition in central nervous system melanoma metastases

Seifert¹,

Hirata

Gore³

et al. 2015

Pigment Cell Melanoma Res

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“…(Caron et al,2009) Other potential markers of oxidative stress include tumor necrosis factor- (TNF-)α, interleukins and c-reactive protein. (Mazur et al,2004; Protas et al,2011) Longitudinal studies are needed to determine whether the acute and chronic dysregulation of inflammatory biomarkers can predict long-term effects on ALL survivors’ cognitive function.…”

Section: Discussionmentioning

confidence: 99%

Neurocognitive outcomes in long-term survivors of childhood acute lymphoblastic leukemia treated on contemporary treatment protocols: A systematic review

Cheung

Krull

2015

Neuroscience & Biobehavioral Reviews

144

145

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The intensified administration of chemotherapeutic drugs has gradually replaced cranial radiation therapy (CRT) for the treatment of childhood acute lymphoblastic leukemia (ALL). While CRT is often implicated in neurocognitive impairment in ALL survivors, there is a paucity of literature that evaluates the persistence of neurocognitive deficits in long-term survivors of pediatric ALL who were treated with contemporary chemotherapy-only protocols. Results from this systematic review concurred to the probable cognitive-sparing effect of chemotherapy-based protocols over CRT in long-term survivors. However, coupled with multiple intrinsic and extrinsic factors, survivors who received chemotherapy treatment still suffered from apparent cognitive impairment, particularly in the attention and executive function domains. Notably, there is evidence to suggest that the late neurotoxic effect of methotrexate on survivors’ neurocognitive performance may be dose-related. This review also recommends future pharmacokinetic, neuroimaging and genetic studies to illuminate the multifactorial nature of this subject matter and discusses the potential value of neurochemical, physiological, inflammatory and genetic markers for the prediction of susceptibility to neurocognitive impairment in long-term survivors of childhood ALL.

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“…While elevated IL-6, IL-17, and IL-18 levels at birth have been associated with increased risk of developing B-cell ALL later in life, their exact role in ALL development, if any, is unknown [ 67 , 96 ]. Elevated levels of TNFα and CCL2 in the cerebrospinal fluid of patients with ALL were initially linked to a higher risk of relapse, but these levels were later found to be related to intrathecal chemotherapy [ 98 , 99 , 100 , 101 ].…”

Section: Potential Mechanisms By Which Obesity May Contribute To Amentioning

confidence: 99%

Is There a Causal Relationship between Childhood Obesity and Acute Lymphoblastic Leukemia? A Review

Dushnicky

Nazarali

Mir

et al. 2020

Cancers

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Childhood obesity is a growing epidemic with numerous global health implications. Over the past few years, novel insights have emerged about the contribution of adult obesity to cancer risk, but the evidence base is far more limited in children. While pediatric patients with acute lymphoblastic leukemia (ALL) are at risk of obesity, it is unclear if there are potential causal mechanisms by which obesity leads to ALL development. This review explores the endocrine, metabolic and immune dysregulation triggered by obesity and its potential role in pediatric ALL’s genesis. We describe possible mechanisms, including adipose tissue attraction and protection of lymphoblasts, and their impact on ALL chemotherapies’ pharmacokinetics. We also explore the potential contribution of cytokines, growth factors, natural killer cells and adipose stem cells to ALL initiation and propagation. While there are no current definite causal links between obesity and ALL, critical questions persist as to whether the adipose tissue microenvironment and endocrine actions can play a causal role in childhood ALL, and there is a need for more research to address these questions.

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Cerebrospinal Fluid IL-6, TNF-α and MCP-1 in Children with Acute Lymphoblastic Leukaemia during Chemotherapy

Cited by 10 publications

References 7 publications

Extrinsic factors can mediate resistance to BRAF inhibition in central nervous system melanoma metastases

Extrinsic factors can mediate resistance to BRAF inhibition in central nervous system melanoma metastases

Neurocognitive outcomes in long-term survivors of childhood acute lymphoblastic leukemia treated on contemporary treatment protocols: A systematic review

Is There a Causal Relationship between Childhood Obesity and Acute Lymphoblastic Leukemia? A Review

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