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Summary: Chronic myelomonocytic leukaemia (CMML) is a rare haematological disorder characterized by monocytosis and dysplastic changes in myeloid cell lineages. Accurate risk stratification is essential for guiding treatment decisions and assessing prognosis. This study aimed to validate the Artificial Intelligence Prognostic Scoring System for Myelodysplastic Syndromes (AIPSS‐MDS) in CMML and to assess its performance compared with traditional scores using data from a Spanish registry (n = 1343) and a Taiwanese hospital (n = 75). In the Spanish cohort, the AIPSS‐MDS accurately predicted overall survival (OS) and leukaemia‐free survival (LFS), outperforming the Revised‐IPSS score. Similarly, in the Taiwanese cohort, the AIPSS‐MDS demonstrated accurate predictions for OS and LFS, showing superiority over the IPSS score and performing better than the CPSS and molecular CPSS scores in differentiating patient outcomes. The consistent performance of the AIPSS‐MDS across both cohorts highlights its generalizability. Its adoption as a valuable tool for personalized treatment decision‐making in CMML enables clinicians to identify high‐risk patients who may benefit from different therapeutic interventions. Future studies should explore the integration of genetic information into the AIPSS‐MDS to further refine risk stratification in CMML and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndromes (MDS) are a group of clinically and genetically diverse diseases that impose patients with an increased risk of leukemic transformation. While MDS is a disease of the elderly, the interplay between aging and molecular profiles is not fully understood, especially in the Asian population. Thus, we compared the genetic landscape between younger and older patients in a cohort of 698 patients with primary MDS to advance our understanding of the distinct pathogenesis and different survival impacts of gene mutations in MDS according to age. We found that the average mutation number was higher in the older patients than younger ones. The younger patients had more WT1 and CBL mutations, but less mutated ASXL1, DNMT3A, TET2, SF3B1, SRSF2, STAG2, and TP53 than the older patients. In multivariable survival analysis, RUNX1 mutations with higher variant allele frequency (VAF) and U2AF1 and TP53 mutations were independent poor prognostic indicators in the younger patients, whereas DNMT3A and IDH2 mutations with higher VAF and TP53 mutations conferred inferior outcomes in the older patients. In conclusion, we demonstrated the distinct genetic landscape between younger and older patients with MDS and suggested that mutations impact survival in an age‐depended manner. [ABSTRACT FROM AUTHOR]

Summary: Leukaemic stem cell (LSC) gene expression has recently been linked to prognosis in patients with acute myeloid leukaemia (17‐gene LSC score, LSC‐17) and myelodysplastic syndromes. Although chronic myelomonocytic leukaemia (CMML) is regarded as a stem cell disorder, the clinical and biological impact of LSCs on CMML patients remains elusive. Making use of multiple independent validation cohorts, we here describe a concise three‐gene expression signature (LSC‐3, derived from the LSC‐17 score) as an independent and robust prognostic factor for leukaemia‐free and overall survival in CMML. We propose that LSC‐3 could be used to supplement existing risk stratification systems, to improve prognostic performance and guide management decisions. [ABSTRACT FROM AUTHOR]

Summary: Increasing evidence supports the role of the immune microenvironment and associated signalling in the pathogenesis of myelodysplastic syndromes (MDS). Nevertheless, the clinical relevancy of immune signals in patients with MDS remains elusive. To address this, we used single‐sample gene‐set enrichment analysis to score immune signatures of bone marrow (BM) samples from 176 patients with primary MDS. Enhanced signatures of 'immature dendritic cells' and 'natural killer cells with cluster of differentiation (CD)56bright' were correlated with better overall survival (OS), whilst higher 'CD103+ signature' was associated with reduced survival. An MDS‐Immune‐Risk (MIR) scoring system was constructed based on the weighted sums derived from Cox regression analysis. High MIR scores were correlated with higher revised International Prognostic Scoring System (IPSS‐R) scores and mutations in ASXL transcriptional regulator 1 (ASXL1), Runt‐related transcription factor 1 (RUNX1), and tumour protein p53 (TP53). High‐score patients had significantly inferior leukaemia‐free survival (LFS) and OS than low‐score patients. The prognostic significance of MIR scores for survival remained valid across IPSS‐R subgroups and was validated in two independent cohorts. Multivariable analysis revealed that a higher MIR score was an independent adverse risk factor for LFS and OS. We further proposed a model with the combination of MIR score and gene mutations to be complementary to IPSS‐R for the prognostication of LFS and OS of patients with MDS. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndromes/neoplasms (MDS) and acute myeloid leukaemia (AML) are neoplastic haematopoietic cell proliferations that are diagnosed and classified based on a combination of morphological, clinical and genetic features. Specifically, the percentage of myeloblasts in the blood and bone marrow is a key feature that has historically separated MDS from AML and, together with several other morphological parameters, defines distinct disease entities within MDS. Both MDS and AML have recurrent genetic abnormalities that are increasingly influencing their definitions and subclassification. For example, in 2022, two new MDS entities were recognised based on the presence of SF3B1 mutation or bi‐allelic TP53 abnormalities. Genomic information is more objective and reproducible than morphological analyses, which are subject to interobserver variability and arbitrary numeric cut‐offs. Nevertheless, the integration of genomic data with traditional morphological features in myeloid neoplasm classification has proved challenging by virtue of its sheer complexity; gene expression and methylation profiling also can provide information regarding disease pathogenesis, adding to the complexity. New machine‐learning technologies have the potential to effectively integrate multiple diagnostic modalities and improve on historical classification systems. Going forward, the application of machine learning and advanced statistical methods to large patient cohorts can refine future classifications by advancing unbiased and robust previously unrecognised disease subgroups. Future classifications will probably incorporate these newer technologies and higher‐level analyses that emphasise genomic disease entities over traditional morphologically defined entities, thus promoting more accurate diagnosis and patient risk stratification. [ABSTRACT FROM AUTHOR]

Summary: Long non‐coding RNAs (lncRNAs) have important functions in cancer biology. Among them, lncRNA KIAA0125 is one of the genes proposed to play a critical role in leukaemia stem cell (LSC). In this study, we aimed to investigate the clinical relevance of the expression levels of lncRNA KIAA0125 in myelodysplastic syndromes (MDS), a disease with highly heterogeneous clinical and biological features. Using RNA arrays, we measured the expression of KIAA0125 in 176 primary MDS patients. We found that higher KIAA0125 expression was associated with higher risk MDS, based on the revised International Prognostic Scoring System (IPSS‐R), mutations in ASXL1 and NRAS, and predicted poorer overall survival (OS) and leukaemia‐free survival (LFS). Multivariate analysis revealed that higher KIAA0125 expression was an independent, unfavourable prognostic factor for OS and LFS, irrespective of IPSS‐R and mutation status. Further global gene expression profile analysis suggested a close association of higher KIAA0125 expressions with LSC signatures. The expression of KIAA0125 may be a potential biomarker to guide the treatment choice in MDS patients, especially those with lower risk subtypes, in whom palliative treatment is usually used. [ABSTRACT FROM AUTHOR]

Background: Far-infrared radiation (FIR) therapy improves vessel dilation, circulation, vessel endothelial function, and angiogenesis and reduces atherosclerosis. However, evidence of FIR therapy's effects on foot circulation among diabetic patients undergoing hemodialysis is scarce. Aim: To determine whether FIR therapy improves foot circulation in diabetic patients undergoing hemodialysis. Design: Quasi-experimental. Methods: In June to November 2017, diabetic patients undergoing hemodialysis (N = 58) at a hemodialysis center in northern Taiwan were divided into two groups: the experimental group (n = 31) received FIR therapy to the bilateral dorsalis pedis artery (40 min/session, 3 times/week for 6 months) and the control group (n = 27) received conventional dialysis care. Paired t test, independent samples t test, two-proportion Z test, and repeated-measures analysis of covariance were performed to compare changes from baseline to the end of the 6-month intervention between the groups. Results: Significant positive effects of FIR therapy on temperature, pulse, and blood flow of the dorsalis pedis artery were observed. Sensitivity to pain, tactility, and pressure also improved significantly in the experimental group. The Edinburgh Claudication Questionnaire revealed that the experimental group had reductions in subjective experiences of soreness, tingling, and coldness in the feet. Conclusion: The findings of significant improvements to objective and subjective measures of blood flow and neural function in the experimental group indicate that FIR therapy improves blood circulation to the feet. This therapy thus has great potential to be an effective adjuvant treatment for patients with diabetes mellitus undergoing hemodialysis. [ABSTRACT FROM AUTHOR]

The allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is viewed as the ultimate cure for acute lymphoblastic leukemia (ALL). An essential component of allo-HSCT is the conditioning regimen administered before the hematopoietic stem-cell infusion. This study is aimed to compare outcomes of ALL patients receiving either a busulfan with cyclophosphamide (BuCy) or a total body irradiation(TBI)-based regimen. We retrospectively analyzed data from National Taiwan University Hospital institute registry. We enrolled 224 adult patients with ALL who received allo-HSCT between 1997 and 2016 and compared outcomes of patients receiving either a BuCy-based or a TBI-based regimen. There were more B-cell ALL than T-cell ALL (67.8% vs 32.2%). A total of 41 patients (22.5%) carried the Philadelphia chromosome (Ph) while 38 patients (20.9%) carried complex karyotype. Before the allo-HSCT, 164 (73.2%) patients achieved first or late complete remission (CR). The main source of stem-cell was from peripheral blood (71%), followed by bone marrow (22.3%). Siblings comprised 54.9% of the donors. A total of 141 patients (63%) received BuCy-based conditioning, either myeloablative (MA) or reduced intensity stem cell transplantation (RIST) and 83 patients (37%) received TBI-based regimen. The mean dose of stem cell was 4.96 ± 2.42 × 106/Kg CD34+ cells. We use cyclosporine and mycophenolate mofetil for prophylaxis of graft-versus-host disease (GvHD). In results, patients received BuCy-based regimen performed as well as TBI-based group in terms of 5-year overall survival (47.5% vs 37.3%, p =0.115). As to 5-year relapse-free survival (RFS), BuCy group had slightly better result, especially the group received myeloablative conditioning (MA, Bu-based vs. MA, TBI-based, p =0.059), albeit the p value didn¡¦t reach significance, the curves went on departing ways. In this study, all regimen groups yielded similar treatment-related mortality (TRM), (MA, Bu-based vs RIST, Bu-based vs MA, TBI-based: 17% vs 10.9% vs 21.7%, p =0.308) and incidences of grade 3-4 acute GvHD at day+100, (p =0.445). Further, in patients with extramedullary disease, there was no difference among groups; and interestingly, BuCy group with MA conditioning seemed to yield better result than TBI group (p =0.072). By multi-variate analysis, disease status before allo-HSCT is the only risk factor impacting OS and RFS. In conclusion, patients received BuCy-based regimen or TBI-based regimen as conditioning had similar results in terms of OS, RFS, TRM, and GvHD. [ABSTRACT FROM AUTHOR]

In addition to high-molecular risk (HMR) mutations (ASXL1, EZH2, SRSF2, IDH, and U2AF1 Q157 ), lower JAK2V617F variant allele frequencies (VAF) have been demonstrated to be associated with poor prognosis of myelofibrosis (MF) patients. Nevertheless, the relationship between JAK2V617F VAF and HMR mutations remains inconclusive. To address this, we analyzed the mutation status of 54 myeloid neoplasm-relevant genes using targeted next-generation sequencing in 124 MF patients. Three cohorts from multiple international centers were analyzed for external validation. Among JAK2-mutated patients, the presence of HMR mutations drove poor prognosis in patients with lower JAK2V617F VAF but not in those with higher JAK2V617F VAF. Survival analyses showed consistent results across validation cohorts. In multivariable analysis, concurrent HMR and a lower JAK2V617F VAF was identified as an independent adverse prognostic factor for survival, irrespective of age, MIPSS70, MIPSS70 + v2, and GIPSS risk groups. Mutation co-occurrence tests revealed no shared mutational pattern over different cohorts, excluding potential confounding effect from other concurrent mutations. Importantly, the integration of HMR/JAK2V617F VAF (≤50%) status significantly enhanced existing prognostic models, as evidenced by higher c-indexes and time-dependent ROC analyses. Single-cell studies with sequential follow-ups are warranted to decipher the clonal evolution of MF and how it relates to JAK2V617F VAF dynamics., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

This study conducted adsorption experiments using Europium (Eu(III)) on geological materials collected from Taiwan. Batch tests on argillite, basalt, granite, and biotite showed that argillite and basalt exhibited strong adsorption reactions with Eu. X-ray diffraction (XRD) analysis also clearly indicated differences before and after adsorption. By combining X-ray absorption near-edge structure (XANES), extended X-ray absorption fine structure (EXAFS), and wavelet transform (WT) analyses, we observed that the Fe 2 O 3 content significantly affects the Eu-Fe distance in the inner-sphere layer during the Eu adsorption process. The wavelet transform analysis for two-dimensional information helps differentiate two distances of Eu-O, which are difficult to analyze, with hydrated outer-sphere Eu-O distances ranging from 2.42 to 2.52 Å and inner-sphere Eu-O distances from 2.27 to 2.32 Å. The EXAFS results for Fe 2 O 3 and SiO 2 in argillite and basalt reveal different adsorption mechanisms. Fe 2 O 3 exhibits inner-sphere surface complexation in the order of basalt, argillite, and granite, while SiO 2 forms outer-sphere ion exchange with basalt and argillite. Wavelet transform analysis also highlights the differences among these materials.

Myelodysplastic syndrome (MDS) comprised a heterogeneous group of diseases. The prognosis of patients varies even in the same risk groups. Searching for novel prognostic markers is warranted. Leukemic stem cells (LSCs) are responsible for chemoresistance and relapse in leukemia. Recently, expressions of 17 genes related to stemness of LSCs were found to be associated with prognosis in acute myeloid leukemia patients. However, the clinical impact of LSC genes expressions in MDS, a disorder arising from hematopoietic stem cells, remains unclear. We analyzed expression profile of the 17 stemness-related genes in primary MDS patients and identified expression of 4 genes (LAPTM4B, NGFRAP1, EMP1, and CPXM1) were significantly correlated with overall survival (OS). We constructed an LSC4 scoring system based on the weighted sums of the expression of 4 genes and explored its clinical implications in MDS patients. Higher LSC4 scores were associated with higher revised International Prognostic Scoring System (IPSS-R) scores, complex cytogenetics, and mutations in RUNX1, ASXL1, and TP53. High-score patients had significantly shorter OS and leukemia-free survival (LFS), which was also confirmed in 2 independent validation cohorts. Subgroup analysis revealed the prognostic significance of LSC4 scores for OS remained valid across IPSS-R lower- and higher-risk groups. Furthermore, higher LSC4 score was an independent adverse risk factor for OS and LFS in multivariate analysis. In summary, LSC4 score can independently predict prognosis in MDS patients irrespective of IPSS-R risks and may be used to guide the treatment of MDS patients, especially lower-risk group in whom usually only supportive treatment is given., (© 2020 by The American Society of Hematology.)

This study demonstrates a novel cell manipulation microdevice for cell docking, culturing, cell-cell contact and interaction by microfluidic manipulation of heterogeneous cell suspensions. Heterogeneous cell suspensions include disparate blood cells of natural killer cells and leukemia cancer cells for immune cell transplantation therapy. However, NK cell alloreactivity from different healthy donors present various recovery response levels. Little is still known about the interactions and cytotoxicity effects between donor NK cells and recipient cancer cells. The cell-based micro device first showed the capability of cell docking, movement, contact and cell-cell interaction with respect to cell cytotoxicity of NK cells against cancer cells. With various flow tests for live cell loading, flow rates of 10 μL/h were chosen for injection in the central and side flows such that both types of suspension cells could be gently docked at the gap structure in a reaction zone. The trapping number of particles and cells was linearly proportional to the gap length. Finally, the cytotoxicity of around 40% was found to be similar in the case of dilute cells and a large cell population. As a result, the cell manipulation microdevice has been validated for live suspensions of natural killer and cancer cells, and exhibited the capability to measure the cytotoxicity of dilute cell suspensions.