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Summary The homeodomain protein homeobox (HOPX), a multifaceted regulator of cellular functions and developmental processes, is predominantly expressed in stem cells across diverse tissues; it has also emerged as a tumour suppressor in various solid cancers. However, its role in haematological malignancies still remains undefined. This study aimed to elucidate its significance in T‐cell acute lymphoblastic leukaemia (T‐ALL). We firstly uncovered a novel link between reduced HOPX expression, its promoter hypermethylation and increased tumour burden in patients with T‐ALL, suggesting its tumour‐suppressive role. Next, we induced T‐ALL by transducing intracellular NOTCH1 (ICN1) into mice with either conditional knock‐in at the Rosa26 locus or knockout of Hopx. We found that T‐ALL development was markedly accelerated and impeded in backgrounds with low and high Hopx expression respectively. Further analysis revealed Hopx's roles in modulating the Wnt‐β‐catenin pathway, a pivotal regulator of the downstream Myc signalling involved in T‐ALL transformation and progression. [ABSTRACT FROM AUTHOR]

Summary: Aberrant alternative splicing (AS) contributes to leukemogenesis, but reports on the clinical and biological implications of aberrant AS in acute myeloid leukaemia (AML) remain limited. Here, we used RNA‐seq to analyse AS in AML cells from 341 patients, comparing them to healthy CD34+ haematopoietic stem cells (HSCs). Our findings highlight distinct AS patterns in the nuclear transcription factor Y subunit alpha (NFYA) gene, with two main isoforms: NFYA‐L (Long) and NFYA‐S (Short), differing in exon 3 inclusion. Patients with lower NFYA‐L but higher NFYA‐S expression, termed NFYA‐S predominance, displayed more favourable characteristics and better outcomes following intensive chemotherapy, regardless of age and European LeukemiaNet risk classification, compared to those with higher NFYA‐L but lower NFYA‐S expression, termed NFYA‐L predominance. The prognostic effects were validated using The Cancer Genome Atlas cohort. Transcriptome analysis revealed upregulated cell cycle genes in NFYA‐S predominant cases, resembling those of active HSCs, demonstrating relative chemosensitivity. Conversely, NFYA‐L predominant cases, as observed in KMT2A‐rearranged leukaemia, were associated with relative chemoresistance. NFYA‐S overexpression in OCI‐AML3 cells promoted cell proliferation, S‐phase entry and increased cytarabine sensitivity, suggesting its clinical and therapeutic relevance in AML. Our study underscores NFYA AS as a potential prognostic biomarker in AML. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Primary gastric diffuse large B‐cell lymphoma (DLBCL), a rare malignancy linked to Helicobacter pylori (HP) infection, in this case regressed to low‐grade lymphoma and then achieved complete remission after HP eradication (HPE), highlighting this unique interim change and the potential of HPE as an effective treatment for early‐stage cases. Primary gastric diffuse large B‐cell lymphoma (DLBCL) is a rare malignancy. Like gastric mucosa‐associated lymphoid tissue (MALT) lymphoma, HP infection is implicated in lymphomagenesis and has thus emerged as a therapeutic target. Studies have demonstrated the sustained efficacy of HP eradication alone for limited‐stage primary gastric DLBCL. This report presents the case of a 53‐year‐old woman with stage IE gastric DLBCL who received triple therapy for HP eradication and experienced an interim histological transformation to MALT lymphoma, ultimately achieving complete pathologic remission. HP eradication therapy may represent a viable treatment option for patients with early‐stage primary gastric DLBCL. [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]

We present the case of a 70‐year‐old man diagnosed with acute myelomonocytic leukemia, albeit that his leukemic blasts at initial presentation had scant cytoplasm, inconspicuous cytoplasmic granules, and morphologically mimicked lymphoblasts. We would like to raise the recognition that acute myelomonocytic leukemia can actually present with atypical blast morphology. [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]

Myeloproliferative neoplasms (MPNs) are characterized by upregulation of proinflammatory cytokines and immune dysregulation, which provide a reasonable basis for immunotherapy in patients. Megakaryocytes are crucial in the pathogenesis of primary myelofibrosis (PMF), the most clinically aggressive subtype of MPN. In this study, we aimed to explore PD‐L1 (programmed death‐ligand 1) expression in megakaryocytes and its clinical implications in PMF. We analyzed PD‐L1 expression on megakaryocytes in PMF patients by immunohistochemistry and correlated the results with clinicopathological features and molecular aberrations. We employed a two‐tier grading system considering both the proportion of cells positively stained and the intensity of staining. Among the 85 PMF patients, 41 (48%) showed positive PD‐L1 expression on megakaryocytes with the immune‐reactive score ranging from 1 to 12. PD‐L1 expression correlated closely with higher white blood cell count (p = 0.045), overt myelofibrosis (p = 0.010), JAK2V617F mutation (p = 0.011), and high‐molecular risk mutations (p = 0.045), leading to less favorable overall survival in these patients (hazard ratio 0.341, 95% CI 0.135–0.863, p = 0.023). Our study provides unique insights into the interaction between immunologic and molecular phenotypes in PMF patients. Future work to explore the translational potential of PD‐L1 in the clinical setting is needed. [ABSTRACT FROM AUTHOR]

Objective: To identify determinants of shared decision making in patients with multiple myeloma (MM) to facilitate the design of a program to maximize the effects of shared decision making.Methods: This prospective longitudinal study recruited 276 adult patients (52% male, mean age 62.86 y, SD 15.45). Each patient completed the eHealth Literacy Scale (eHEALS), Multidimensional Trust in Health Care Systems Scale (MTHCSS), Patient Communication Pattern Scale (PCPS), and 9-Item Shared Decision-Making Questionnaire (SDM-Q-9) at baseline and the SDM-Q-9 again 6 months later. One family member of the patient completed the Family Decision-Making Self-Efficacy (FDMSE) at baseline. Structural equation modeling (SEM) was used to investigate the associations between eHealth literacy (eHEALS), trust in the health care system (MTHCSS), self-efficacy in family decision making (FDMSE), patient communication pattern (PCPS), and shared decision making (SDM-Q-9).Results: SEM showed satisfactory fit (comparative fit index = 0.988) and significant correlations between the following: eHealth literacy and trust in the health care system (β = 0.723, P < 0.001); eHealth literacy and patient communication pattern (β = 0.242, P < 0.001); trust in the health care system and patient communication pattern (β = 0.397, P < 0.001); self-efficacy in family decision making and patient communication pattern (β = 0.264, P < 0.001); eHealth literacy and shared decision making (β = 0.267, P < 0.001); and patient communication pattern and shared decision making (β = 0.349, P < 0.001).Conclusions: Patient communication and eHealth literacy were found to be important determinants of shared decision making. These factors should be taken into consideration when developing strategies to enhance the level of shared decision making. [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]

Primary pulmonary lymphoma is an uncommon disease, and extranodal marginal zone lymphoma of mucosa‐associated lymphoid tissue (MALT) is the most common type of pulmonary lymphoma. The most frequent pattern observed in chest computed tomography (CT) is consolidation, followed by nodules and mass. The differentiation of pulmonary MALT lymphoma from other lung diseases is critical for disease management and treatment. However, pulmonary MALT lymphoma with isolated endobronchial manifestation has seldomly been reported. Here, we report a case of an elderly woman who presented with a four‐month history of cough, dyspnoea, and haemoptysis. Chest CT scan revealed left main bronchus narrowing without lung parenchymal lesion. Bronchoscopic examination was performed, and the diagnosis of primary pulmonary MALT lymphoma with isolated endobronchial involvement was made. She has been successfully treated with rituximab.We describe a case of primary pulmonary mucosa‐associated lymphoid tissue (MALT) lymphoma presented as an endobronchial tumor without lung parenchymal involvement. [ABSTRACT FROM AUTHOR]

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., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)