Strong Homology Between Colonizing and Bloodstream Carbapenem-Resistant Acinetobacter Spp.: Implications for Empiric Antibiotic Therapy in Hematological Patients.

Objective: This study aimed to assess the impact of colonization status on the outcomes of Acinetobacter spp. bloodstream infection (BSI) and investigate the homology and within-host evolution between colonizing and bloodstream carbapenem-resistant Acinetobacter spp. (CRA) to inform antibiotic therapeutic decisions. Methods: We analyzed clinical outcomes of 46 hematological patients with Acinetobacter spp. BSI and performed whole-genome sequencing on the remaining CRA isolates. Results: Among the patients, 39.1% (n=18) had prior Acinetobacter spp. colonization. Colonized patients had higher rates of polymicrobial BSI (50.0% vs 21.4%, P=0.044) and CRA BSI (72.2% vs 17.9%, P<0.001), resulting in elevated inflammatory markers and increased 30-day mortality. Each of the eight pairs of the remaining respiratory colonizing and bloodstream CRA strains belonged to the same genomospecies. Each pair exhibited definitive agreement in at least 21 of the 22 most representative antibiotic susceptibility tests. The minimum spanning tree based on multilocus sequence typing (MLST) and phylogenetic trees based on MLST and single nucleotide polymorphism (SNP) all indicated that each pair shared the same minimum branch. Very few non-synonymous SNPs in genic regions were identified during the transition from respiratory colonization to bloodstream infection, with minimal changes in virulence genes. Homology analysis suggested that CRA BSI originated from colonizing isolates in the respiratory tract. Conclusion: Strict infection control measures are needed to manage Acinetobacter spp. colonisation in hematological patients. Appropriate empirical therapy can be administered for suspected CRA BSI based on the antimicrobial minimum inhibitory concentration of CRA colonising the respiratory tract.

Minimal residual disease monitoring in childhood Philadelphia chromosome-positive acute lymphoblastic leukemia: prognostic significance and correlation between multiparameter flow cytometry and real-time quantitative polymerase chain reaction

Not available.

Gene expression prognostic of early relapse risk in low-risk B-cell acute lymphoblastic leukaemia in children.

ETV6::RUNX1 is the most common fusion gene in childhood acute lymphoblastic leukaemia (ALL) and is associated with favorable outcomes, especially in low-risk children. However, as many as 10% of children relapse within 3 years, and such early relapses have poor survival. Identifying children at risk for early relapse is an important challenge. We interrogated data from 87 children with low-risk ETV6::RUNX1-positive B-cell ALL and with available preserved bone marrow samples (discovery cohort). We profiled somatic point mutations in a panel of 559 genes and genome-wide transcriptome and single-nucleotide variants. We found high TIMD4 expression (> 85th-percentile value) at diagnosis was the most important independent prognostic factor of early relapse (hazard ratio [HR] = 5.07 [1.76, 14.62]; p = 0.03). In an independent validation cohort of low-risk ETV6::RUNX1-positive B-cell ALL (N = 68) high TIMD4 expression at diagnosis had an HR = 4.78 [1.07, 21.36] (p = 0.04) for early relapse. In another validation cohort including 78 children with low-risk ETV6::RUNX1-negative B-cell ALL, high TIMD4 expression at diagnosis had an HR = 3.93 [1.31, 11.79] (p = 0.01). Our results suggest high TIMD4 expression at diagnosis in low-risk B-cell ALL in children might be associated with high risk for early relapse.

Single-cell systems pharmacology identifies development-driven drug response and combination therapy in B cell acute lymphoblastic leukemia.

Leukemia can arise at various stages of the hematopoietic differentiation hierarchy, but the impact of developmental arrest on drug sensitivity is unclear. Applying network-based analyses to single-cell transcriptomes of human B cells, we define genome-wide signaling circuitry for each B cell differentiation stage. Using this reference, we comprehensively map the developmental states of B cell acute lymphoblastic leukemia (B-ALL), revealing its strong correlation with sensitivity to asparaginase, a commonly used chemotherapeutic agent. Single-cell multi-omics analyses of primary B-ALL blasts reveal marked intra-leukemia heterogeneity in asparaginase response: resistance is linked to pre-pro-B-like cells, with sensitivity associated with the pro-B-like population. By targeting BCL2, a driver within the pre-pro-B-like cell signaling network, we find that venetoclax significantly potentiates asparaginase efficacy in vitro and in vivo. These findings demonstrate a single-cell systems pharmacology framework to predict effective combination therapies based on intra-leukemia heterogeneity in developmental state, with potentially broad applications beyond B-ALL.

Outcome of infants with acute lymphoblastic leukemia treated with the Chinese Children's Cancer Group Acute Lymphoblastic Leukemia 2015 study protocol.

Not available.

The elevation of red blood cell distribution width is an independent prognostic factor for juvenile myelomonocytic leukemia.

Juvenile myelomonocytic leukemia (JMML) is a disorder characterized by the simultaneous presence of myeloproliferative and myelodysplastic features, primarily affecting infants and young children. Due to the heterogeneous genetic background among patients, the current clinical and laboratory prognostic features are insufficient for accurately predicting outcomes. Thus, there is a pressing need to identify novel prognostic indicators. Red cell distribution width (RDW) is a critical parameter reflecting the variability in erythrocyte size. Recent studies have emphasized that elevated RDW serves as a valuable predictive marker for unfavorable outcomes across various diseases. However, the prognostic role of RDW in JMML remains unclear. Patients with JMML from our single-center cohort between January 2008 and December 2019 were included. Overall, 77 patients were eligible. Multivariate Cox proportional hazard models showed that patients with red cell distribution width coefficient of variation (RDW-CV) >17.35% at diagnosis were susceptible to much worse overall survival rate (hazard ratio [HR] = 5.22, confidence interval [CI] = 1.50-18.21, P = .010). Besides, the combination of RDW elevation and protein phosphatase non-receptor type 11 (PTPN11) mutation was likely to predict a subgroup with the worst outcomes in our cohort. RDW is an independent prognostic variable in JMML subjects. RDW may be regarded as an inexpensive biomarker to predict the clinical outcome in patients with JMML.

[Two cases of cytopenia associated with multiple malformations]. / 血细胞减少伴多发畸形2例.

The first patient, a 10-year-old girl, presented with pancytopenia and recurrent epistaxis, along with a history of repeated upper respiratory infections, café-au-lait spots, and microcephaly. Genetic testing revealed compound heterozygous mutations in the DNA ligase IV (LIG4) gene, leading to a diagnosis of LIG4 syndrome. The second patient, a 6-year-old girl, was seen for persistent thrombocytopenia lasting over two years and was noted to have short stature, hyperpigmented skin, and hand malformations. She had a positive result from chromosome breakage test. She was diagnosed with Fanconi anemia complementation group A. Despite similar clinical presentations, the two children were diagnosed with different disorders, suggesting that children with hemocytopenia and malformations should not only be evaluated for hematological diseases but also be screened for other potential underlying conditions such as immune system disorders.

Efficacy, Safety, and Population Pharmacokinetics of Eltrombopag in Children with Different Severities of Aplastic Anemia.

Eltrombopag was approved as a first-line treatment for patients older than 2 years old with severe aplastic anemia (SAA). However, data on eltrombopag in children with different types of aplastic anemia (AA), especially non-severe AA (NSAA), are limited. We performed a prospective, single-arm, and observational study to investigate eltrombopag's efficacy, safety, and pharmacokinetics in children with NSAA, SAA, and very severe AA (VSAA). The efficacy and safety were assessed every 3 months. The population pharmacokinetic (PPK) model was used to depict the pharmacokinetic profile of eltrombopag. Twenty-three AA children with an average age of 7.9 (range of 3.0-14.0) years were enrolled. The response (complete and partial response) rate was 12.5%, 50.0%, and 100.0% after 3, 6, and 12 months in patients with NSAA. For patients with SAA and VSAA, these response rates were 46.7%, 61.5%, and 87.5%. Hepatotoxicity occurred in one patient. Fifty-three blood samples were used to build the PPK model. Body weight was the only covariate for apparent clearance (CL/F) and volume of distribution. The allele-T carrier of adenosine triphosphate-binding cassette transporter G2 was found to increase eltrombopag's clearance. However, when normalized by weight, the clearance between the wild-type and variant showed no statistical difference. In patients with response, children with NSAA exhibited lower area under the curve from time zero to infinity, higher CL/F, and higher weight-adjusted CL/F than those with SAA or VSAA. However, the differences were not statistically significant. The results may support further individualized treatment of eltrombopag in children with AA.

Biodegradation of microplastics derived from controlled release fertilizer coating: Selective microbial colonization and metabolism in plastisphere.

Coated controlled-release fertilizers (CRFs) are widely used in agriculture, and the persistent presence of residual polymer coating has raised environmental concerns. This study investigates the underlying degradation dynamics of microplastics (MPs) derived from three typical materials used in CRFs, including polyethylene (PE), epoxy (EP), and polyurethane (PU), through a soil degradation test. The formation of surface biofilm, the succession process, and metabolic characteristics of microbial community are revealed by laser scanning confocal microscope, 16S rRNA sequencing, and non-targeted metabolomics analysis. The weight loss rates of PE, EP, and PU after 807 days of degradation were 16.70 %, 2.79 %, and 4.86 %, respectively. Significant secondary MPs were produced with tears and holes appeared in the coating cross sections and pyrolysis products were produced such as ethers, acids, and esters for PE; alkanes, olefins and their branched-chain derivatives for EP; and short-chain fatty acids and benzene molecules for PU. The coating surface selectively recruited the bacteria of Chujaibacter and Ralstonia and fungus of Fusarium and Penicillium, forming biofilm composed of lipids, proteins, and living cells. The metabolism of amino acids and polymers was enhanced to protect against MP-induced stress. The metabolites or intermediates of organic acids and derivatives, oxygen-contained organic compounds, and benzenoids on CRF surface increased significantly compared with soil, but there were no significant differences among different coating types. This study provides insights to the underlying mechanisms of biodegradation and microenvironmental changes of MPs in soil.

Decitabine-containing conditioning improved outcomes for children with higher-risk myelodysplastic syndrome undergoing allogeneic hematopoietic stem cell transplantation.

Myelodysplastic syndrome (MDS) is a rare clonal hematopoietic disorder in children. The risk stratification system and treatment strategy for adults are unfit for children. The role of hypomethylating agents (HMAs) in higher-risk childhood MDS has not been identified. This study aimed to investigate the outcomes of hematopoietic stem cell transplantation (HSCT) in children with higher-risk MDS at one single center. A retrospective study was conducted in children with higher-risk MDS undergoing HSCT between September 2019 and March 2023 at Blood Diseases Hospital CAMS. The clinical characteristics and transplantation information were reviewed and analyzed. A total of 27 patients were analyzed, including 11 with MDS with excess blasts (MDS-EB), 14 with MDS-EB in transformation (MDS-EBt) or acute myeloid leukemia with myelodysplasia-related changes (AML-MRC), and 2 with therapy-related MDS/AML (t-MDS/AML). Eight patients harbored monosomy 7. Before transplantation, induction therapy was administered to 25 patients, and 19 of them achieved bone marrow blasts <5% before HSCT. The stem cell source was unmanipulated-related bone marrow or peripheral blood stem cells for nineteen patients and unrelated cord blood for eight. All patients received decitabine-containing and Bu/Cy-based myeloablative conditioning; 26 patients achieved initial engraftment. The cumulative incidences of grade II-IV and grade III-IV acute graft-versus-host disease (GvHD) at 100 days were 65.4% and 42.3%, respectively. The incidence of cGvHD was 38.5%. The median follow-up was 26 (range 4-49) months after transplantation. By the end of follow-up, two patients died of complications and two died of disease progression. The probability of 3-year overall survival (OS) was 84.8% (95%CI, 71.1 to 98.5%). In summary, decitabine-containing myeloablative conditioning resulted in excellent outcomes for children with higher-risk MDS undergoing allogeneic HSCT.

Disruption of mitochondrial energy metabolism is a putative pathogenesis of Diamond-Blackfan anemia.

Energy metabolism in the context of erythropoiesis and related diseases remains largely unexplored. Here, we developed a primary cell model by differentiating hematopoietic stem progenitor cells toward the erythroid lineage and suppressing the mitochondrial oxidative phosphorylation (OXPHOS) pathway. OXPHOS suppression led to differentiation failure of erythroid progenitors and defects in ribosome biogenesis. Ran GTPase-activating protein 1 (RanGAP1) was identified as a target of mitochondrial OXPHOS for ribosomal defects during erythropoiesis. Overexpression of RanGAP1 largely alleviated erythroid defects resulting from OXPHOS suppression. Coenzyme Q10, an activator of OXPHOS, largely rescued erythroid defects and increased RanGAP1 expression. Patients with Diamond-Blackfan anemia (DBA) exhibited OXPHOS suppression and a concomitant suppression of ribosome biogenesis. RNA-seq analysis implied that the substantial mutation (approximately 10%) in OXPHOS genes accounts for OXPHOS suppression in these patients. Conclusively, OXPHOS disruption and the associated disruptive mitochondrial energy metabolism are linked to the pathogenesis of DBA.

Cardiac cell senescence: molecular mechanisms, key proteins and therapeutic targets.

Cardiac aging, particularly cardiac cell senescence, is a natural process that occurs as we age. Heart function gradually declines in old age, leading to continuous heart failure, even in people without a prior history of heart disease. To address this issue and improve cardiac cell function, it is crucial to investigate the molecular mechanisms underlying cardiac senescence. This review summarizes the main mechanisms and key proteins involved in cardiac cell senescence. This review further discusses the molecular modulators of cellular senescence in aging hearts. Furthermore, the discussion will encompass comprehensive descriptions of the key drugs, modes of action and potential targets for intervention in cardiac senescence. By offering a fresh perspective and comprehensive insights into the molecular mechanisms of cardiac senescence, this review seeks to provide a fresh perspective and important theoretical foundations for the development of drugs targeting this condition.

Early Detection of Molecular Residual Disease and Risk Stratification for Children with Acute Myeloid Leukemia via Circulating Tumor DNA.

PURPOSE: Patient-tailored minimal residual disease (MRD) monitoring based on circulating tumor DNA (ctDNA) sequencing of leukemia-specific mutations enables early detection of relapse for pre-emptive treatment, but its utilization in pediatric acute myelogenous leukemia (AML) is scarce. Thus, we aim to examine the role of ctDNA as a prognostic biomarker in monitoring response to the treatment of pediatric AML. EXPERIMENTAL DESIGN: A prospective longitudinal study with 50 children with AML was launched, and sequential bone marrow (BM) and matched plasma samples were collected. The concordance of mutations by next-generation sequencing-based BM-DNA and ctDNA was evaluated. In addition, progression-free survival (PFS) and overall survival (OS) were estimated. RESULTS: In 195 sample pairs from 50 patients, the concordance of leukemia-specific mutations between ctDNA and BM-DNA was 92.8%. Patients with undetectable ctDNA were linked to improved OS and PFS versus detectable ctDNA in the last sampling (both P < 0.001). Patients who cleared their ctDNA post three cycles of treatment had similar PFS compared with persistently negative ctDNA (P = 0.728). In addition, patients with >3 log reduction but without clearance in ctDNA were associated with an improved PFS as were patients with ctDNA clearance (P = 0.564). CONCLUSIONS: Thus, ctDNA-based MRD monitoring appears to be a promising option to complement the overall assessment of pediatric patients with AML, wherein patients with continuous ctDNA negativity have the option for treatment de-escalation in subsequent therapy. Importantly, patients with >3 log reduction but without clearance in ctDNA may not require an aggressive treatment plan due to improved survival, but this needs further study to delineate.

Assessing patterns of delirium symptoms reveals a novel subtype among elective surgical patients with postoperative delirium.

OBJECTIVES: Prior studies reported incidence of hypoactive and hyperactive subtypes of postoperative delirium, but did not consider cognitive symptoms of delirium which are highlighted in the DSM-5 criteria for delirium. This study aims to address this gap in the literature by classifying cases of delirium according to their constellation of cognitive and motoric symptoms of delirium using a statistical technique called Latent Class Analysis (LCA). METHODS: Data were from five independent study cohorts (N = 1968) of patients who underwent elective spine, knee/hip, or elective gastrointestinal and thoracic procedures, between 2001 and 2017. Assessments of delirium symptoms were conducted using the long form of the Confusion Assessment Method (CAM) pre- and post-surgery. Latent class analyses of CAM data from the first 2 days after surgery were conducted to determine subtypes of delirium based on patterns of cognitive and motoric symptoms of delirium. We also determined perioperative patient characteristics associated with each latent class of delirium and assessed whether the length of delirium for each of the patterns of delirium symptoms identified by the latent class analysis. RESULTS: The latent class model from postoperative day 1 revealed three distinct patterns of delirium symptoms. One pattern of symptoms, denoted as the Hyperalert class, included patients whose predominant symptoms were being hyperalert or overly sensitive to environmental stimuli and having a low level of motor activity. Another pattern of symptoms, denoted as the Hypoalert class, included patients whose predominant symptom was being hypoalert (lethargic or drowsy). A third pattern of symptoms, denoted as the Cognitive Changes class, included patients who experienced new onset of disorganized thinking, memory impairment, and disorientation. Among 352 patients who met CAM criteria for delirium on postoperative day 1, 34% had symptoms that fit within the Hyperalert latent class, 39% had symptoms that fit within the Hypoalert latent class, and 27% had symptoms that fit within the Cognitive Changes latent class. Similar findings were found when latent class analysis was applied to those who met CAM criteria for delirium on postoperative day 2. Multinomial regression analyses revealed that ASA class, surgery type, and preoperative cognitive status as measured by the Telephone Interview for Cognitive Status (TICS) scores were associated with class membership. Length of delirium differed between the latent classes with the Cognitive Changes latent class having a longer duration compared to the other two classes. CONCLUSIONS: Older elective surgery patients who did not have acute events or illnesses or a diagnosis of dementia prior to surgery displayed varying symptoms of delirium after surgery. Compared to prior studies that described hypoactive and hyperactive subtypes of delirium, we identified a novel subtype of delirium that reflects cognitive symptoms of delirium. The three subtypes of delirium reveal distinct patterns of delirium symptoms which provide insight into varying risks and care needs of patients with delirium, indicating the necessity of future research on reducing risk for cognitive symptoms of delirium.

CRISPR/Cas9-mediated SERS/colorimetric dual-mode lateral flow platform combined with smartphone for rapid and sensitive detection of Staphylococcus aureus.

Pathogenic bacteria infections pose a significant threat to global public health, making the development of rapid and reliable detection methods urgent. Here, we developed a surface-enhanced Raman scattering (SERS) and colorimetric dual-mode platform, termed smartphone-integrated CRISPR/Cas9-mediated lateral flow strip (SCC-LFS), and applied it to the ultrasensitive detection of Staphylococcus aureus (S. aureus). Strategically, functionalized silver-coated gold nanostar (AuNS@Ag) was prepared and used as the labeling material for LFS assay. In the presence of S. aureus, target gene-induced amplicons can be accurately recognized and unwound by the user-defined CRISPR/Cas9 system, forming intermediate bridges that bind many AuNS@Ag to the test line (T-line) of the strip. As a result, the T-line was colored and a recognizable SERS signal was obtained using a smartphone-integrated portable Raman spectrometer. This design not only maintains the simplicity of visual readout, but also integrates the quantitative capability of SERS, enabling the user to flexibly select the assay mode as needed. With this method, S. aureus down to 1 CFU/mL can be detected by both colorimetric and SERS modes, which is better than most existing methods. By incorporating a rapid extraction procedure, the entire assay can be completed in 45 min. The robustness and practicality of the method were further demonstrated by various real samples, indicating its considerable potential toward reliable screening of S. aureus.

Individualized Use of 6-Mercaptopurine in Chinese Children with ALL: A Multicenter Randomized Controlled Trial.

Continuous 6-mercaptopurine (6-MP) dose titration is necessary because of its narrow therapeutic index and frequently encountered dose-limiting hematopoietic toxicity. However, evidence-based guidelines for gene-based 6-MP dosing have not been established for Chinese children with acute lymphoblastic leukemia (ALL). This multicenter, randomized, open-label, active-controlled clinical trial randomly assigned Chinese children with low- or intermediate-risk ALL in a 1:1 ratio to receive TPMT-NUDT15 gene-based dosing of 6-MP (N = 44, 10 to 50 mg/m2 /day) or standard dosing (N = 44, 50 mg/m2 /day) during maintenance therapy. The primary end point was the incidence of 6-MP myelosuppression in both groups. Secondary end points included frequencies of 6-MP hepatotoxicity, duration of myelosuppression and leukopenia, event-free survival, and steady-state concentrations of active metabolites (6-thioguaninenucleotides and 6-methylmercaptopurine nucleotides) in erythrocytes. A 2.2-fold decrease in myelosuppression, the primary end point, was observed in the gene-based-dose group using ~ 50% of the standard initial 6-MP dose (odds ratio, 0.26, 95% confidence interval, 0.11 to 0.64, P = 0.003). Patients in the gene-based-dose group had a significantly lower risk of developing thiopurine-induced myelosuppression and leukopenia (P = 0.015 and P = 0.022, respectively). No significant differences were observed in the secondary end points of the incidence of hepatotoxicity and steady-state concentrations of active metabolites in erythrocytes between the two groups. TPMT- and NUDT15-based dosing of 6-MP will significantly contribute toward further reducing the incidence of leukopenia in Chinese children with ALL. This trial is registered at www.clinicaltrial.gov as #NCT04228393.

Clonal evolution dissection reveals that a high MSI2 level promotes chemoresistance in T-cell acute lymphoblastic leukemia.

ABSTRACT: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive cancer with resistant clonal propagation in recurrence. We performed high-throughput droplet-based 5' single-cell RNA with paired T-cell receptor (TCR) sequencing of paired diagnosis-relapse (Dx_Rel) T-ALL samples to dissect the clonal diversities. Two leukemic evolutionary patterns, "clonal shift" and "clonal drift" were unveiled. Targeted single-cell DNA sequencing of paired Dx_Rel T-ALL samples further corroborated the existence of the 2 contrasting clonal evolution patterns, revealing that dynamic transcriptional variation might cause the mutationally static clones to evolve chemotherapy resistance. Analysis of commonly enriched drifted gene signatures showed expression of the RNA-binding protein MSI2 was significantly upregulated in the persistent TCR clonotypes at relapse. Integrated in vitro and in vivo functional studies suggested that MSI2 contributed to the proliferation of T-ALL and promoted chemotherapy resistance through the posttranscriptional regulation of MYC, pinpointing MSI2 as an informative biomarker and novel therapeutic target in T-ALL.

Outcome of first or second transplantation using unrelated umbilical cord blood without ATG conditioning regimen for pediatric bone marrow failure disorders.

BACKGROUND: Unrelated umbilical cord blood transplantation (UCBT) for bone marrow failure (BMF) disorders using conditioning regimens without Anti-Thymocyte Globulin (ATG) has been used as an alternative transplantation for emerging patients without matched-sibling donors. Experience with this transplant modality in children is limited, especially as a secondary treatment for transplant failure patients. PROCEDURE: We retrospectively reviewed 17 consecutive bone marrow failure patients who underwent unrelated umbilical cord blood transplantation in our center and received conditioning regimens of Total Body Irradiation (TBI) or Busulfan (BU) + Fludarabine (FLU) + Cyclophosphamide (CY). RESULTS: Among the 17 BMF patients, 15 patients were treated with first cord blood transplantation and another 2 with secondary cord blood transplantation because of graft failure after first haploidentical stem cell transplantation at days +38 and +82. All patients engrafted with a median donor cell chimerism of 50 % at days +7 (range, 16 %-99.95 %) and finally rose to 100 % at days +30. Median time to neutrophil engraftment was 19 days (range, 12-30) and time to platelet engraftment was 32 days (range, 18-61). Pre-engraftment syndrome (PES) was found in 16 patients (94.11 %, 16/17). Cumulative incidence of grades II to IV acute GVHD was 58.8 % (95 % CI: 32.7-84.9 %), and 17.6 % (95 % CI: 2.6-37.9 %) of patients developed chronic GVHD. The 3-year overall survival (OS) and failure-free survival (FFS) rates were 92.86 ± 6.88 %. CONCLUSION: UCBT is an effective alternative treatment for bone marrow failure pediatric patients. TBI/BU + FLU + CY regimen ensure a high engraftment rate for unrelated umbilical cord blood transplantation, which overcomes the difficulty of graft failure. Secondary salvage use of cord blood transplantation may still be useful for patients who have failed after other transplantation.

Iron chelation improves ineffective erythropoiesis and iron overload in myelodysplastic syndrome mice.

Myelodysplastic syndrome (MDS) is a heterogeneous group of bone marrow stem cell disorders characterized by ineffective hematopoiesis and cytopenias, most commonly anemia. Red cell transfusion therapy for anemia in MDS results in iron overload, correlating with reduced overall survival. Whether the treatment of iron overload benefits MDS patients remains controversial. We evaluate underlying iron-related pathophysiology and the effect of iron chelation using deferiprone on erythropoiesis in NUP98-HOXD13 transgenic mice, a highly penetrant well-established MDS mouse model. Our results characterize an iron overload phenotype with aberrant erythropoiesis in these mice which was reversed by deferiprone-treatment. Serum erythropoietin levels decreased while erythroblast erythropoietin receptor expression increased in deferiprone-treated MDS mice. We demonstrate, for the first time, normalized expression of the iron chaperones Pcbp1 and Ncoa4 and increased ferritin stores in late-stage erythroblasts from deferiprone-treated MDS mice, evidence of aberrant iron trafficking in MDS erythroblasts. Importantly, erythroblast ferritin is increased in response to deferiprone, correlating with decreased erythroblast ROS. Finally, we confirmed increased expression of genes involved in iron uptake, sensing, and trafficking in stem and progenitor cells from MDS patients. Taken together, our findings provide evidence that erythroblast-specific iron metabolism is a novel potential therapeutic target to reverse ineffective erythropoiesis in MDS.