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Acute myeloid leukemia (AML) is a deadly form of leukemia with ineffective traditional treatment and frequent chemoresistance-associated relapse. Personalized drug screening holds promise in identifying optimal regimen, nevertheless, primary AML cells undergo spontaneous apoptosis during cultures, invalidating the drug screening results. Here, we reconstitute a 3D osteogenic niche (3DON) mimicking that in bone marrow to support primary AML cell survival and phenotype maintenance in cultures. Specifically, 3DON derived from osteogenically differentiated mesenchymal stem cells (MSC) from healthy and AML donors are co-cultured with primary AML cells. The AML cells under the AML_3DON niche showed enhanced viability, reduced apoptosis and maintained CD33+ CD34-phenotype, associating with elevated secretion of anti-apoptotic cytokines in the AML_3DON niche. Moreover, AML cells under the AML_3DON niche exhibited low sensitivity to two FDA-approved chemotherapeutic drugs, further suggesting the physiological resemblance of the AML_3DON niche. Most interestingly, AML cells co-cultured with the healthy_3DON niche are highly sensitive to the same sample drugs. This study demonstrates the differential responses of AML cells towards leukemic and healthy bone marrow niches, suggesting the impact of native cancer cell niche in drug screening, and the potential of re-engineering healthy bone marrow niche in AML patients as chemotherapeutic adjuvants overcoming chemoresistance, respectively.

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The HLA-A*23:140 allele differs from HLA-A*23:01:01 by one nucleotide substitution (G > A), position 1968 in exon 5.

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Acute myeloid leukemia (AML) is a predominant form of leukemia. Central nervous system (CNS) involvement complicates its diagnosis due to limited diagnostic tools, as well as its treatment due to inadequate therapeutic methodologies and poor prognosis. Furthermore, its incidence rate is unclear. The mechanisms of AML cell mobilization from the bone marrow (BM) to the CNS are not fully elucidated, and the molecular factors contributing to CNS infiltration are insufficiently recognized. The present review aimed to enhance the understanding of CNS involvement of AML and its impact on CNS. The latest research on the pathways and mechanisms facilitating AML cells to escape the BM and infiltrate the CNS was reviewed. Additionally, novel therapeutic strategies targeting specific molecules and genes for treating CNS involvement in AML were examined.

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Bone marrow biopsy (BMB) is a routinely performed procedure, with the preferred site being the posterior superior iliac crest. Uncommonly, it may be complicated by haemorrhagic complications, especially in patients with coagulopathy. Here, we present a case of pelvic haematoma following a BMB due to the injury of the right internal iliac artery. Endovascular embolisation was performed on an urgent basis to manage this complication. The bleeding stopped following the embolisation.

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BACKGROUND: It has been described in mice models that myeloproliferative neoplasm (MPN) with JAK2-V617F mutation has an increased expression of programmed death-ligand 1 (PD-L1) in megakaryocytes leading to cancer immune evasion by inhibiting the T-lymphocytes. AIMS: To quantify and compare the PD-L1 expression on bone marrow (BM) of patients with MPN JAK2 positive, negative, and normal controls. METHODS: We collected BM of patients with MPN JAK2 positive, negative and normal controls from 1990 to 2019. We also created a scoring system to quantify PD-L1 expression in megakaryocytes. RESULTS: We obtained 14 BM with JAK2 positive PMF, 5 JAK2 negative PMF, and 10 patients with normal BM biopsies. PD-L1 expression was higher in the JAK2 positive group compared with the control group with a score of 212.6 versus 121.1 (t-value 2.05, p-value 0.025). In addition, the score was higher in the PMF group regardless of JAK2 mutational status when compared with the control group with score of 205.9 versus 121.1 (t-value 2.12, p-value 0.021). There was no difference in the PD-L1 score between the JAK2 negative versus the control group 187.2 versus 121.1 (t-value 1.02, p-value 0.162). CONCLUSION: These findings suggest that PMF patients with a JAK2 mutation have a higher PD-L1 expression in megakaryocytes compared with the control group. We postulate that the combination of checkpoint and JAK2 inhibitors may be an active treatment option in JAK2 mutated PMF given the higher PD-L1 expression.

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Extracellular vesicles (EVs) are heterogeneous, phospholipid membrane enclosed particles that are secreted by healthy and cancerous cells. EVs are present in diverse biological fluids and have been associated with the severity of diseases, which indicates their potential as biomarkers for diagnosis, prognosis and as therapeutic targets. This study investigated the phenotypic characteristics of EVs derived from peripheral blood (PB) and bone marrow (BM) in pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL) during different treatment stages. PB and BM plasma were collected from 20 B-ALL patients at three time points during induction therapy, referred to as: diagnosis baseline (D0), day 15 of induction therapy (D15) and the end of the induction therapy (D35). In addition, PB samples were collected from 10 healthy children at a single time point. The EVs were measured using CytoFLEX S flow cytometer. Calibration beads were employed to ensure accurate size analysis. The following, fluorescent-labeled specific cellular markers were used to label the EVs: Annexin V (phosphatidylserine), CD235a (erythrocyte), CD41a (platelet), CD51 (endothelial cell), CD45 (leukocyte), CD66b (neutrophil), CD14 (monocyte), CD3 (T lymphocyte), CD19, CD34 and CD10 (B lymphoblast/leukemic blast). Our results demonstrate that B-ALL patients had a marked production of EV-CD51/61+, EV-CD10+, EV-CD19+ and EV-CD10+CD19+ (double-positive) with a decrease in EV-CD41a+ on D0. However, the kinetics and signature of production during induction therapy revealed a clear decline in EV-CD10+ and EV-CD19+, with an increase of EV-CD41a+ on D35. Furthermore, B-ALL patients showed a complex biological network, exhibiting distinct profiles on D0 and D35. Interestingly, fold change and ROC curve analysis demonstrated that EV-CD10+CD19+ were associated with B-ALL patients, exhibited excellent clinical performance and standing out as a potential diagnostic biomarker. In conclusion, our data indicate that EVs represent a promising field of investigation in B-ALL, offering the possibility of identifying potential biomarkers and therapeutic targets.

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Mutational profiles of myelodysplastic syndromes (MDS) have established that a relatively small number of genetic aberrations, including SF3B1 and SRSF2 spliceosome mutations, lead to specific phenotypes and prognostic subgrouping. We performed a multi-omics factor analysis (MOFA) on two published MDS cohorts of bone marrow mononuclear cells (BMMNCs) and CD34 + cells with three data modalities (clinical, genotype, and transcriptomics). Seven different views, including immune profile, inflammation/aging, retrotransposon (RTE) expression, and cell-type composition, were derived from these modalities to identify the latent factors with significant impact on MDS prognosis. SF3B1 was the only mutation among 13 mutations in the BMMNC cohort, indicating a significant association with high inflammation. This trend was also observed to a lesser extent in the CD34 + cohort. Interestingly, the MOFA factor representing the inflammation shows a good prognosis for MDS patients with high inflammation. In contrast, SRSF2 mutant cases show a granulocyte-monocyte progenitor (GMP) pattern and high levels of senescence, immunosenescence, and malignant myeloid cells, consistent with their poor prognosis. Furthermore, MOFA identified RTE expression as a risk factor for MDS. This work elucidates the efficacy of our integrative approach to assess the MDS risk that goes beyond all the scoring systems described thus far for MDS.

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Serous atrophy of bone marrow (SABM) is characterized by focal replacement of bone marrow elements with extracellular gelatinous substances. It has been associated with a wide range of chronic conditions, including anorexia nervosa, malignancy, chronic kidney disease, and certain chronic infections. Previous literature has reported the disorder as primarily diagnosed via bone marrow biopsy and occurring outside of the distal extremities. Herein we describe a case of SABM occurring in the feet diagnosed via magnetic resonance imaging (MRI), a phenomenon that is rarely reported. The patient is a 45-year-old woman with a history of end-stage renal disease, congestive heart failure, type 2 diabetes, and peripheral arterial disease who initially presented with nonhealing, bilateral foot ulcers. She subsequently underwent several podiatric medical surgeries due to persistent foot infections and poor wound healing. During her most recent hospitalization, MRIs of her feet were obtained, and findings of abnormal bone marrow signal were attributed to technical malfunction of the MRI coil or scanner. After troubleshooting sources of malfunction, a repeated MRI of the foot was obtained and again demonstrated the same bone marrow signal abnormalities; at this time, SABM was diagnosed. Knowledge of this condition can prevent the misinterpretation of SABM on MRI and prevent the waste of time and medical resources.

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BACKGROUND: Acute lymphoblastic leukemia is the most common pediatric malignancy, characterized by fever, anemia, hemorrhage, and symptoms brought on by blasts infiltrating organs. CASE PRESENTATION: This is a case report of a 9-year-old Asian patient with acute lymphoblastic leukemia who presented with polyuria alone as a presenting feature without any other clinical manifestation; primary renal disease or inherited metabolic disease was highly suspected. However, the water deprivation test and water deprivation pressurization test suggested nephrogenic diabetes insipidus, and the renal biopsy displayed diffuse lymphocytic infiltration in the renal interstitium. Bone marrow aspiration was performed immediately, and a comprehensive diagnosis of B-lymphoblastic leukemia was finally made. CONCLUSIONS: Renal infiltration with leukemic blasts mostly remains asymptomatic, but our case suggests that it can present with nephrogenic diabetes insipidus. This case fully demonstrates that the presentation of extramedullary infiltration in acute lymphoblastic leukemia is varied. When the patient has renal diabetes insipidus as the first symptom, the possibility of hematological tumor infiltration should be considered when finding the cause, and timely bone marrow cytology should be performed.

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OBJECTIVE: We aimed to evaluate the diagnostic performance of dual-energy computed tomography (DECT) in detecting bone marrow edema (BME) in patients with lower limb joint injuries. METHODS: A thorough literature search was conducted across the PubMed, Embase, and Web of Science databases to identify relevant studies up to April 2024. Studies examining the diagnostic performance of DECT in detecting BME in lower limb joint injuries patients were included. Sensitivity and specificity were evaluated using the inverse variance method and transformed via the Freeman-Tukey double arcsine transformation. Furthermore, the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was utilized to evaluate the methodological quality of the included studies. RESULTS: This meta-analysis included 17 articles involving 625 patients. The pooled sensitivity, specificity, and AUC for DECT in detecting BME in lower limb joint injuries patients were 0.82 (95 % CI: 0.76-0.87), 0.95 (95 % CI: 0.92-0.97), and 0.95 (95 % CI: 0.93-0.97), respectively. The pooled sensitivity of DECT for detecting BME in knee, hip, and ankle joint injuries was 0.80, 0.84, and 0.80, with no significant difference among these joints (P = 0.55). The pooled specificity for knee, hip, and ankle injuries was 0.95, 0.97, and 0.89. Specificity differed significantly among the joints (P < 0.01), with the highest specificity in hip injuries. CONCLUSIONS: Our meta-analysis indicates that DECT demonstrates high diagnostic performance in detecting BME in patients with lower limb joint injuries, with the highest specificity observed in hip joint injuries. To validate these findings, further larger prospective studies are necessary.

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BACKGROUND: Interferon gamma release assay (IGRA) is an important method to detect the specific antigen of tuberculosis, which is crucial to the diagnosis of tuberculosis or potential tuberculosis infection. METHODS: We report a case of myelosuppression caused by the use of Melphalan in the treatment of multiple myeloma, resulting in an abnormal decrease in interferon gamma release assay results. RESULTS: We collected blood samples from the patient for retesting and the result of the test did not differ significantly. Upon reviewing the case, it was found that the patient's use of Melphalan treatment resulted in bone marrow suppression and extreme reduction of peripheral blood lymphocytes. Therefore, it is speculated that the abnormal decrease of the interferon gamma release assay result is caused by bone marrow suppression, which is caused by the use of Melphalan. CONCLUSIONS: When patients with multiple myeloma are treated with Melphalan, it can lead to bone marrow suppression and result in false negative interference gamma release assay results. Laboratory staff should consider the existence of such interference and communicate with clinical doctors in a timely manner.

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BACKGROUND: This study aimed to assess the expression level of upstream stimulator 1 (USF1) in the bone marrow of newly diagnosed acute myeloid leukemia (AML) patients and investigate its clinical and prognostic significance. METHODS: Bone marrow samples from 60 newly diagnosed AML patients constituted the observation group, while 20 samples from healthy individuals formed the control group. Real-time quantitative PCR (qRT-PCR) was used to measure the USF1 expression in both groups and to analyze its correlation with clinicopathological features and prognosis in AML patients. Kaplan-Meier curves were utilized to assess the impact of USF1 on the overall survival (OS) in AML patients. The prognostic factors of AML were examined by using Cox regression analysis. RESULTS: A univariate analysis revealed a significantly higher USF1 expression in the AML patients compared to the control group (p < 0.001), with no difference in the clinicopathological features between the low-expression group and the control group. However, there was a significant difference between the high-expression group and the control group (p < 0.01). Moreover, the OS of the high USF1 expression group was notably shorter than of the low USF1 expression group (p < 0.0001). A multivariate analysis identified high USF1 expression and age ≥ 60 years as independent risk factors for a poor AML prognosis. CONCLUSIONS: High expression of USF1 is linked to a worse prognosis and shorter survival time in AML patients. USF1 may serve as an indicator of prognosis and survival in AML patients and could be a potential target for AML treatment.

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Myeloid malignancies arise in bone marrow microenvironments and shape these microenvironments in favor of malignant development. Immune suppression is one of the most important stages in myeloid leukemia progression. Leukemic clone expansion and immune dysregulation occur simultaneously in bone marrow microenvironments. Complex interactions emerge between normal immune system elements and leukemic clones in the bone marrow. In recent years, researchers have identified several of these pathological interactions. For instance, recent works shows that the secretion of inflammatory cytokines such as tumor necrosis factor-α (TNF-α), from bone marrow stromal cells contributes to immune dysregulation and the selective proliferation of JAK2V617F+ clones in myeloproliferative neoplasms. Moreover, inflammasome activation and sterile inflammation result in inflamed microenvironments and the development of myelodysplastic syndromes. Additional immune dysregulations, such as exhaustion of T and NK cells, an increase in regulatory T cells, and impairments in antigen presentation are common findings in myeloid malignancies. In this review, we discuss the role of altered bone marrow microenvironments in the induction of immune dysregulations that accompany myeloid malignancies. We also consider both current and novel therapeutic strategies to restore normal immune system function in the context of myeloid malignancies.

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A single nucleotide mismatch within exon 3 of HLA-DQA1 differentiates the novel allele DQA1*03:79 from DQA1*03:15.

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Tumor-associated neutrophil (TAN) effects on glioblastoma (GBM) biology remain under-characterized. We show here that neutrophils with dendritic features-including morphological complexity, expression of antigen presentation genes, and the ability to process exogenous peptide and stimulate major histocompatibility complex (MHC)II-dependent T cell activation-accumulate intratumorally and suppress tumor growth in vivo. Trajectory analysis of patient TAN scRNA-seq identifies this "hybrid" dendritic-neutrophil phenotype as a polarization state that is distinct from canonical cytotoxic TANs, and which differentiates from local precursors. These hybrid-inducible immature neutrophils-which we identified in patient and murine glioblastomas-arise not from circulation, but from local skull marrow. Through labeled skull flap transplantation and targeted ablation, we characterize calvarial marrow as a contributor of antitumoral myeloid antigen-presenting cells (APCs), including TANs, which elicit T cell cytotoxicity and memory. As such, agents augmenting neutrophil egress from skull marrow-such as intracalvarial AMD3100, whose survival-prolonging effect in GBM we report-present therapeutic potential.

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OBJECTIVE: To evaluate early bone marrow microvascular changes in alloxan-induced diabetic rabbits using IDEAL-IQ fat quantification, texture analysis based on DCE-MRI Ktrans map, and metabolomics. MATERIALS AND METHODS: 24 male Japanese rabbits were randomly divided into diabetic (n = 12) and control (n = 12) groups. All rabbits underwent sagittal MRI of the lumbar vertebrae at the 0th,4th, 8th, 12th, and 16th week, respectively. The fat fraction (FF) ratio and quantitative permeability of the lumbar bone marrow was measured. Texture parameters were extracted from DCE-MRI Ktrans map. At 16th week, lumbar vertebrae 5 and 6 were used for histological analysis. Lumbar vertebra 7 was crushed to obtain bone marrow for metabolomics research. RESULTS: The FF ratio and Ktrans of the lumbar bone marrow in diabetic group were increased significantly at 16th week (t = 2.226, P = 0.02; Z = -2.721, P < 0.01). Nine texture feature parameters based on DCE-MRI Ktrans map were significantly different between the groups at the 16th week (all P < 0.05). Pathway analysis showed that diabetic bone marrow microvascular changes were mainly related to linoleic acid metabolism. Differential metabolites were correlated with the number of adipocytes, FF ratio, and permeability parameters. CONCLUSION: The integration of metabolomics with texture analysis based on DCE-MRI Ktrans map may be used to evaluate diabetic bone marrow microvascular changes at an early stage. It remains to be validated in clinical studies whether the integration of metabolomics with texture analysis based on the DCE-MRI Ktrans map can effectively evaluate diabetic bone marrow.

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Iron is a vital element involved in a plethora of metabolic activities. Mammalian systemic iron homeostasis is mainly modulated by hepcidin, the synthesis of which is regulated by a number of proteins, including the hemochromatosis-associated proteins Hfe and Transferrin Receptor 2 (TfR2). Macrophages play versatile functions in iron homeostasis by storing iron derived from the catabolism of erythrocytes and supplying iron required for erythropoiesis. The absence of Hfe in macrophages causes a mild iron deficiency in aged mice and leads to an overproduction of the iron exporter Ferroportin 1 (Fpn1). Conversely, TfR2 gene silencing in macrophages does not influence systemic iron metabolism but decreases transcription of the macrophage Fpn1 in adult mice and modulates their immune response. This study investigated cellular and systemic iron metabolism in adult and aged male mice with macrophage-specific Hfe and TfR2 silencing (double knock-out, DKO). Serum iron parameters were significantly modified in aged animals, and significant differences were found in hepatic hepcidin transcription at both ages. Interestingly, splenic iron content was low in adult DKOs and splenic Fpn1 transcription was significantly increased in DKO animals at both ages, while the protein amount does not reflect the transcriptional trend. Additionally, DKO macrophages were isolated from mice bone marrow (BMDMs) and showed significant variations in the transcription of iron genes and protein amounts in targeted mice compared to controls. Specifically, Tranferrin Receptor 1 (TfR1) increased in DKO adult mice BMDMs, while the opposite is observed in the cells of aged DKO mice. Fpn1 transcript was significantly decreased in the BMDMs of adult DKO mice, while the protein was reduced at both ages. Lastly, a significant increase in Erythropoietin production was evidenced in aged DKO mice. Overall, our study reveals that Hfe and TfR2 in macrophages regulate hepatic Hepc production and affect iron homeostasis in the spleen and BMDMs, leading to an iron deficiency in aged animals that impairs their erythropoiesis.

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Identification of driver genes and pathological bone marrow diagnosis were considered essential for subclassification of MPN in the revised 4th edition of the WHO classification, and this remained nearly unchanged in the 5th edition. Pathological diagnosis of primary myelofibrosis/pre-fibrotic stage by biopsy is now feasible and is becoming standardized. Progressive myelofibrosis and blast transformation are the advanced forms of MPN, and various therapeutic interventions for these forms have been devised. Observation of activated megakaryocytes on evaluation of megakaryocyte morphology could predict the progression of myelofibrosis. This paper describes recent progress in pathological diagnosis of MPN and how it is performed in practice.

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Objective: To study the expressions of C-C class chemokine 17 (CCL17), C-C class chemokine 22 (CCL22), and C-C chemokine receptor 4 (CCR4) in newly diagnosed multiple myeloma (NDMM) for analyzing their correlations with clinical features and to preliminarily explore their roles in the development of NDMM. Methods: The study included 40 patients with NDMM and 20 healthy volunteers from the Department of Hematology of the Affiliated Hospital of Zunyi Medical University from July 2020 to December 2022. Peripheral blood, bone marrow, and bone marrow biopsy tissue samples were collected from the two groups. The expression levels of CCL17, CCL22, and CCR4 in patients with NDMM were analyzed using real-time quantitative reverse transcriptase polymerase chain reaction (RQ-PCR), enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry. The mRNA expression levels of CCL17, CCL22, and CCR4 in the bone marrow mononuclear cell (BMMNC) of patients with NDMM were analyzed to assess their correlations with clinical indicators. Results: The mRNA expression levels of CCL17, CCL22, and CCR4 in BMMNC were higher in patients with NDMM than in controls (all P<0.05). The protein expression levels of CCL17 and CCL22 in peripheral blood supernatants and bone marrow supernatants were higher in patients with NDMM than in controls (all P<0.05). The expression levels of CCL17, CCL22, and CCR4 in bone marrow biopsy tissues were higher in patients with NDMM than in controls (all P<0.05). The mRNA expression level of CCL17 was increased in NDMM patients with combined anemia, bone damage, renal damage, and M protein level ≥30 g/L (all P<0.05). The mRNA expression level of CCL22 was increased in NDMM patients with combined anemia, bone damage, and renal damage (all P<0.05). The mRNA expression level of CCR4 was increased in NDMM patients with combined anemia and renal damage (all P<0.05) . Conclusion: CCL17, CCL22, and CCR4 were highly expressed in clinical samples from patients with NDMM compared to those from controls, and they may be involved in the occurrence and development of NDMM.

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