Anemia is frequently observed in patients with cancer owing to anticancer chemotherapy, radiation therapy, and inflammatory responses. This often leads to functional iron deficiency, characterized by adequate iron stores but impaired use of iron for red blood cell production. This condition, termed functional iron deficiency anemia (IDA), is identified by a ferritin level of 30–500 µg/dL and a transferrin saturation < 50%. Functional iron deficiency often develops with the prolonged use of erythropoiesis-stimulating agents, leading to a diminished response to anemia treatment. Although oral iron supplementation is common, intravenous iron is more effective and recommended in such cases. Recent studies have shown that ferric carboxymaltose (FCM) is effective in treating functional IDA in patients with cancer. However, because of its potential to induce asymptomatic severe phosphate deficiency, it is important to closely monitor phosphate levels in patients receiving FCM.

Acute myeloid leukemia (AML) is an aggressive blood cancer with poor clinical outcomes. Emerging data suggest that mitochondrial oxidative phosphorylation (mtOXPHOS) plays a significant role in AML tumorigenesis, progression, and resistance to chemotherapies. However, how the mtOXPHOS is regulated in AML cells is not well understood. In this study, we investigated the oncogenic functions of ERRα in AML by combining in silico, in vitro, and in vivo analyses and showed ERRα is a key regulator of mtOXPHOS in AML cells. The increased ERRα level was associated with worse clinical outcomes of AML patients. Single cell RNA-Seq analysis of human primary AML cells indicated that ERRα-expressing cancer cells had significantly higher mtOXPHOS enrichment scores. Blockade of ERRα by pharmacologic inhibitor (XCT-790) or gene silencing suppressed mtOXPHOS and increased anti-leukemic effects in vitro and in xenograft mouse models.

Fucoidan, a sulfated polysaccharide extracted from brown seaweed, has been proposed to effectively treat and prevent various viral infections. However, the mechanisms behind its antiviral activity are not completely understood. We investigate here the global transcriptional changes in bone marrow-derived dendritic cells (BMDCs) using RNA-Seq technology. Through both analysis of differentially expressed genes (DEG) and gene set enrichment analysis (GSEA), we found that fucoidan-treated BMDCs were enriched in virus-specific response pathways, including that of SARS-CoV-2, as well as pathways associated with nucleic acid-sensing receptors (RLR, TLR, NLR, STING), and type I interferon (IFN) production. We show that these transcriptome changes are driven by well-known regulators of the inflammatory response against viruses, including IRF, NF-κB, and STAT family transcription factors. Furthermore, 435 of the 950 upregulated DEGs are classified as type I IFN-stimulated genes (ISGs). Flow cytometric analysis additionally showed that fucoidan increased MHCII, CD80, and CD40 surface markers in BMDCs, indicative of greater antigen presentation and co-stimulation functionality. Our current study suggests that fucoidan transcriptionally activates PRR signaling, type I IFN production and signaling, ISGs production, and DC maturation, highlighting a potential mechanism of fucoidan-induced antiviral activity.

Lee MW, et al. J Korean Med Sci. 2022 Mar;37(11):e87. https://doi.org/10.3346/jkms.2022.37.e87

Post-transplantation cyclophosphamide (PTCy) and antithymocyte-globulin (ATG) are the most commonly used regimens for prophylaxis of graft-versus-host disease (GVHD). We compared these 2 regimens in human leukocyte antigen (HLA)-matched unrelated donor hematopoietic stem cell transplantation (HSCT) patients with hematological malignancies. We retrospectively analyzed consecutive adult patients with hematological malignancies who underwent HLA-matched unrelated donor-HSCT at Chungnam National University Hospital (Daejeon, South Korea) between January 2013 and January 2019. Patients who received a second transplantation or who had refractory disease were excluded. We included 34 patients (12 and 22 in the PTCy and ATG groups respectively). All graft sources were peripheral blood stem cells. The estimated 20-month overall survival rates were 75.0% for PTCy and 81.6% for ATG patients (P = .792), and the 20-month relapse rates were 41.7% and 34.3% (P = .491), respectively. The cumulative incidences of grade 2 to 4 acute GVHD were 16.7% and 30.6% (P = .551), respectively; the estimated 20-month limited and extensive chronic GVHD rates were 59.1% and 78.8% (P = .718), respectively; and the estimated 20-month extensive chronic GVHD rates were 12.5% and 16.7% (P = .718), respectively. The neutrophil engraftment time was similar in both groups [median (range), 15.0 (12.0–17.0) and 14.0 (12.0–19.0) days, respectively; P = .961]. However, ATG was more expensive than PTCy [median (range), US$4,062 (US$2,215–6,647) for ATG vs US$51.80 (US$43.20–69.20) for PTCy; P < .001]. In conclusion, PTCy and ATG afforded similar clinical outcomes after HLA-matched unrelated donor transplantation but PTCy was less expensive.

Autoimmune limbic encephalitis (LE) is a rare, but devastating complication of allogeneic hematopoietic stem cell transplantation (HSCT). There is currently limited evidence describing the risk factors, laboratory features, and underlying mechanisms of this neurologic adverse event. We retrospectively reviewed available clinical, imaging, and laboratory data from adult patients with hematological malignancies who underwent haploidentical HSCT with post-transplant cyclophosphamide (PTCy) at Chungnam National University Hospital from June 2016 to May 2020. Patients who developed LE were compared to those who did not based on clinical assessment, serum inflammatory biomarkers, and reconstitution of various T cell populations. Of 35 patients, 4 developed LE. There were no differences in patient demographics, donor demographics, or treatment conditions between patients that did and did not develop LE. Overall, patients with LE had worse clinical outcomes and overall survival than those without. In addition, they tended to have higher markers of systemic inflammation in the early post-transplant period, including fever, C-reactive protein (CRP), and cytokines. Remarkably, baseline interleukin-6 levels before HSCT were found to be higher in patients who developed LE than those who did not. In addition, analysis of T cell subsets showed impaired expansion of CD25+FOXP3+ regulatory T (Treg) cells in LE compared to non-LE patients despite appropriate reconstitution of the total CD4+ T cell population. Patients that developed LE within the first 30 days of HSCT were likely to have high serum IL-6 among other inflammatory cytokines coupled with suppression of regulatory T cell differentiation. Further work is needed on the mechanisms underlying impaired Treg expansion following HSCT and potential therapies.