Hemophagocytic lymphohistiocytosis (HLH), also defined as hemophagocytic syndrome (HPS), represents a potentially life-threatening hyperinflammatory syndrome, characterized by impaired function of ...cytotoxic T lymphocytes, natural killer cells and macrophages. The main clinical features of HLH are prolonged fever, hepatosplenomegaly, cytopenia, hypertriglyceridemia, hyperferritinemia and hemophagocytosis in bone marrow, liver, spleen or lymph nodes. Secondary HLH typically occurs in conjunction with severe infections, malignancies or autoimmune disorders and intensive chemotherapy, potentially complicating treatment of acute myeloid leukemia (AML) in around 10% of cases. Herein we report for the first time a case of HLH secondary to refractory/relapsed AML resolved after a second line treatment with azacitidine plus venetoclax, thus offering a new potential therapeutic perspective in the context of a life-threatening clinical scenario.
In the cure of cancer, a major cause of today's mortality, chemotherapy is the most common treatment, though serious frequent challenges are encountered by current anticancer drugs. We discovered ...that few‐layer graphene (FLG) dispersions have a specific killer action on monocytes, showing neither toxic nor activation effects on other immune cells. We confirmed the therapeutic application of graphene on an aggressive type of cancer that is myelomonocytic leukemia, where the monocytes are in their malignant form. We demonstrated that graphene has the unique ability to target and boost specifically the necrosis of monocytic cancer cells. Moreover, the comparison between FLG and a common chemotherapeutic drug, etoposide, confirmed the higher specificity and toxicity of FLG. Since current chemotherapy treatments of leukemia still cause serious problems, these findings open the way to new and safer therapeutic approaches.
Graphene‐based cancer drug: A specific cytotoxic effect of few‐layer graphene on primary human monocytes was discovered. This new biological property of graphene was exploited for cancer therapy. Graphene successfully and selectively boosts the necrosis of monocytoid cancer cells for acute myeloid leukemia and chronic myelomonocytic leukemia patients.
Human hematopoietic stem/progenitor cells (HSPCs) are pluripotent cells that gradually lose their self-renewal and regenerative potential, to give rise to mature cells of the hematopoietic system by ...differentiation. HSPC infusion is used to restore hematopoietic function in patients with a variety of onco-hematologic and immune-mediated disorders. The functionality of these cells is therefore of great importance to ensure the homeostasis of the hematopoietic system. Melatonin plays an important role as immunomodulatory and oncostatic hormone. In the present manuscript, we aimed at evaluating the activity of melatonin in modulating HSPC senescence, in the attempt to improve their hemopoietic regenerative potential. We exposed HSPCs to melatonin, in different conditions, and then analyzed the expression of genes regulating cell cycle and cell senescence. Moreover, we assessed cell senescence by β-galactosidase and telomerase activity. Our results showed the ability of melatonin to counteract HSPC senescence, thus paving the way for enhanced efficiency in their clinical application.
•HSPCs are pluripotent cells, able to differentiate into a series of multipotent progenitors.•Increased ROS production induces DNA damages and is implicated in a wide variety of onco-hematologic disorders.•Melatonin acts as free radical scavenger antioxidant and anti-senescence moleculemolecule.•Melatonin acts by blocking the formation and growth of metastatic cells, or by modifying the cellular microenvironment.
To the Editor:
Duncavage and colleagues (Sept. 13 issue)
1
address the molecular predictors of disease progression and survival among patients with myelodysplastic syndrome (MDS) who underwent ...allogeneic hematopoietic stem-cell transplantation. With the use of enhanced exome sequencing, they found that detection of at least one mutation with a maximum variant allele frequency of at least 0.5% at day 30 after transplantation was associated with a higher risk of progression than the absence of such a mutation. The article offers a new perspective on the understanding of the biologic properties of MDS that may be further explored in the context of . . .
Emerging evidence has proven that human endogenous retroviruses (HERVs) play a critical role in the pathogenesis of Acute Myeloid Leukemia (AML), whereas the specific HERVs influencing the prognosis ...of AML patients have yet to be fully understood.
In this study, a systematic exploration was achieved to identify potential prognostic HERVs for AML, sourced from TCGA and GTEx database. Differential analysis and functional enrichment studies were conducted using GO, KEGG, GSEA, and GSVA. The ESTIMATE algorithm was applied to explore the immune infiltration of HERVs in AML. A prognostic risk-score model was evaluated with predicted yearly accuracy using ROC analysis.
Two HERVs Suppressyn and Syncytin-2, were identified as promising prognostic biomarkers, with high discrimination ability based on ROC analysis between AML and healthy cohorts from TCGA. Their expression was notably higher in AML patients compared to those in healthy individuals but correlates with favorable clinical outcomes in sub-groups such as white race, lower WBC counts, favorable and intermediate risks, and NPM1 or IDH1 mutation. Suppressyn and Syncytin-2 participated in immune-related pathways and exhibited correlations with multiple immune infiltration cells, such as T cells, mast cells, and tumor-associated macrophages. Finally, we developed a prognostic risk-scoring model combining Suppressyn and Syncytin-2, where a high risk-score is associated with better prognosis.
Collectively, our findings revealed that Suppressyn and Syncytin-2 may act as valuable diagnostic and prognostic biomarkers for individuals with AML, while highlighting links between HERV activation, immunogenicity, and future therapeutic targets.
There is paucity of evidence-based data on health-related quality of life (HRQOL) outcomes of chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKIs). We performed a ...multicenter propensity-matched case-control study to compare HRQOL of newly diagnosed CML patients treated with front-line dasatinib (cases) or imatinib (controls). Patient-reported HRQOL was assessed with the EORTC QLQ-C30 and the EORTC QLQ-CML24 questionnaires. The impact on daily life scale of the EORTC QLQ-CML24 was selected a priori in the protocol as the primary HRQOL scale for the comparative analysis. Overall, 323 CML patients were enrolled of whom 223 in therapy with imatinib and 100 in therapy with dasatinib. Patients treated with dasatinib reported better disease-specific HRQOL outcomes in impact on daily life (Δ = 8.72, 95% confidence interval CI: 3.17-14.27, p = 0.002), satisfaction with social life (Δ = 13.45, 95% CI: 5.82-21.08, p = 0.001), and symptom burden (Δ = 7.69, 95% CI: 3.42-11.96, p = 0.001). Analysis by age groups showed that, in patients aged 60 years and over, differences favoring dasatinib were negligible across several cancer generic and disease-specific HRQOL domains. Our findings provide novel comparative HRQOL data that extends knowledge on safety and efficacy of these two TKIs and may help to facilitate first-line treatment decisions.
Nucleophosmin (
) gene mutations rarely occur in non-acute myeloid neoplasms (MNs) with <20% blasts. Among nearly 10,000 patients investigated so far, molecular analyses documented
mutations in ...around 2% of myelodysplastic syndrome (MDS) cases, mainly belonging to MDS with excess of blasts, and 3% of myelodysplastic/myeloproliferative neoplasm (MDS/MPN) cases, prevalently classified as chronic myelomonocytic leukemia. These uncommon malignancies are associated with an aggressive clinical course, relatively rapid progression to overt acute myeloid leukemia (AML) and poor survival outcomes, raising controversies on their classification as distinct clinico-pathologic entities. Furthermore, fit patients with
-mutated MNs with <20% blasts could benefit most from upfront intensive chemotherapy for AML rather than from moderate intensity MDS-directed therapies, although no firm conclusion can currently be drawn on best therapeutic approaches, due to the limited available data, obtained from small and mainly retrospective series. Caution is also suggested in definitely diagnosing
-mutated MNs with blast count <20%, since
-mutated AML cases frequently present dysplastic features and multilineage bone marrow cells showing abnormal cytoplasmic NPM1 protein delocalization by immunohistochemical staining, therefore belonging to
-mutated clone regardless of blast morphology. Further prospective studies are warranted to definitely assess whether
mutations may become sufficient to diagnose AML, irrespective of blast percentage.
Graphene oxide (GO) is attracting great interest in biomedical sciences. The impact of GO on immune cells is one fundamental area of study that is often overlooked, but critical in terms of clinical ...translation. This work investigates the effects of two types of thoroughly characterized GO sheets, different in their lateral dimension, on human peripheral immune cells provided from healthy donors using a wide range of assays. After evaluation of cell viability, the gene expression was analyzed, following GO exposure on 84 genes related to innate and adaptive immune responses. Exposure to GO small sheets was found to have a more significant impact on immune cells compared to GO large sheets, reflected in the upregulation of critical genes implicated in immune responses and the release of cytokines IL1β and TNFα. These findings were further confirmed by whole-genome microarray analysis of the impact of small GO sheets on T cells and monocytes. Activation in both cell types was underlined by the overexpression of genes such as CXCL10 and receptor CXCR3. Significant energy-dependent pathway modulation was identified. These findings can potentially pave the foundations for further design of graphene that can be used for immune modulation applications, for example in cancer immunotherapy.
PDF
