HOPX as a tumour-suppressive protein in T-cell acute lymphoblastic leukaemia.

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).

A machine-learning-based algorithm for bone marrow cell differential counting.

Background: Differential counting (DC) of different cell types in bone marrow (BM) aspiration smears is crucial for diagnosing hematological diseases. However, a clinically applicable method for automatic DC has yet to be developed.

Objective: This study developed and validated an artificial intelligence (AI)-based algorithm for identifying and classifying nucleated cells in BM smears.

Clinical relevance of NFYA splice variants in patients with acute myeloid leukaemia undergoing intensive chemotherapy.

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.

IDH2 mutation accelerates TPO-induced myelofibrosis with enhanced S100a8/a9 and NFκB signaling in vivo.

Introduction: mutation is an unfavorable prognostic factor in patients with primary myelofibrosis (PMF) but its effect on myelofibrosis (MF) remains largely unclear.

Methods: In this study, we aimed to elucidate the roles of mutation in the development and progression of MF by transcriptomic and molecular techniques using the transgenic mice.

Results: We found that thrombopoietin (TPO)-overexpressed ( + TPO) mice had accelerated progression to MF, compared with TPO-overexpressed wild (WT + TPO) mice, showing activation of multiple inflammatory pathways, among which nuclear factor κB (NFκB) was the most significantly enhanced.

Stellae-123 gene expression signature improved risk stratification in taiwanese acute myeloid leukemia patients.

The European Leukemia Net recommendations provide valuable guidance in treatment decisions of patients with acute myeloid leukemia (AML). However, the genetic complexity and heterogeneity of AML are not fully covered, notwithstanding that gene expression analysis is crucial in the risk stratification of AML. The Stellae-123 score, an AI-based model that captures gene expression patterns, has demonstrated robust survival predictions in AML patients across four western-population cohorts.

Kinome expression profiling improves risk stratification and therapeutic targeting in myelodysplastic syndromes.

The human kinome, which comprises >500 kinases, plays a critical role in regulating numerous essential cellular functions. Although the dysregulation of kinases has been observed in various human cancers, the characterization and clinical implications of kinase expressions in myelodysplastic syndromes (MDS) have not been systematically investigated. In this study, we evaluated the kinome expression profiles of 341 adult patients with primary MDS and identified 7 kinases (PTK7, KIT, MAST4, NTRK1, PAK6, CAMK1D, and PRKCZ) whose expression levels were highly predictive of compromised patient survival.

Dysregulated immune and metabolic pathways are associated with poor survival in adult acute myeloid leukemia with CEBPA bZIP in-frame mutations.

Acute myeloid leukemia (AML) with CEBPA bZIP in-frame mutations (CEBPA) is classified within the favorable-risk group by the 2022 European LeukemiaNet (ELN-2022). However, heterogeneous clinical outcomes are still observed in these patients. In this study, we aimed to investigate the mutation profiles and transcriptomic patterns associated with poor outcomes in patients with CEBPA.

Lineage switch of KMT2A-rearranged adult B-lineage acute lymphoblastic leukemia following bispecific T-cell engager and monoclonal antibody therapy.

Adult B-lineage acute lymphoblastic leukemia (B-ALL) with t(4;11)(q21;q23) is very rare. It is characterized by mixed-lineage leukemia and has the potential for lineage switching during the treatment course. We report the disease course of a patient with B-ALL with t(4;11)(q21;q23) to demonstrate that close monitoring of cell morphology and immunophenotyping is necessary to capture the lineage switch at an early stage.

Treatment benefit of upfront autologous stem cell transplantation for newly diagnosed multiple myeloma: a systematic review and meta-analysis.

Background: Upfront high-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) remains a profitable strategy for newly diagnosed multiple myeloma (MM) patients in the context of novel agents. However, current knowledge demonstrates a discrepancy between progression-free survival (PFS) and overall survival (OS) benefit with HDT/ASCT.

Methods: We conducted a systematic review and meta-analysis that included both randomized controlled trials (RCTs) and observational studies evaluating the benefit of upfront HDT/ASCT published during 2012 to 2023.

A case of acute myelomonocytic leukemia morphologically mimicking lymphoblastic leukemia.

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.

Evaluation of the clinical significance of global mRNA alternative splicing in patients with acute myeloid leukemia.

Aberrant alternative splicing (AS) is involved in leukemogenesis. This study explored the clinical impact of alterations in global AS patterns in 341 patients with acute myeloid leukemia (AML) newly diagnosed at the National Taiwan University Hospital and validated it using The Cancer Genome Atlas (TCGA) cohort. While studying normal cord blood CD34 /CD38 cells, we found that AML cells exhibited significantly different global splicing patterns.

A three-gene leukaemic stem cell signature score is robustly prognostic in chronic myelomonocytic leukaemia.

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.

Comparison of chloroplast genomes and phylogenomics in the Ficus sarmentosa complex (Moraceae).

Due to maternal inheritance and minimal rearrangement, the chloroplast genome is an important genetic resource for evolutionary studies. However, the evolutionary dynamics and phylogenetic performance of chloroplast genomes in closely related species are poorly characterized, particularly in taxonomically complex and species-rich groups. The taxonomically unresolved Ficus sarmentosa species complex (Moraceae) comprises approximately 20 taxa with unclear genetic background.

Cerebrospinal fluid soluble programmed death-ligand 1 is a useful prognostic biomarker in primary central nervous system lymphoma.

The increased expression of programmed death-ligands 1 and 2 (PD-L1 and PD-L2, respectively) on tumour cells contributes to immune evasion, suggesting that these proteins are attractive therapeutic targets. This study aimed to evaluate the validity of cerebrospinal fluid (CSF) soluble PD-L1 (sPD-L1) and soluble PD-L2 (sPD-L2) as biomarkers for primary central nervous system lymphoma (PCNSL). We determined the CSF concentrations of sPD-L1 and sPD-L2 in 46 patients with PCNSL using enzyme-linked immunosorbent assays (ELISAs).

Higher expression levels are associated with worse overall and leukaemia-free survival in myelodysplastic syndrome patients.

mutations are frequently detected in various myeloid neoplasms and implicate unfavourable clinical outcomes in patients with myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML). On the other hand, high expression of is also correlated with poor prognosis in AML patients. However, the clinical relevancy of expression in MDS patients remains elusive.

The clinical and biological characterization of acute myeloid leukemia patients with S100A4 overexpression.

Background/purpose: The S100 family proteins are involved in a variety of important biological processes, most notably immune and inflammatory responses. Their dysregulation also plays a role in the pathogenesis of human cancers. S100A4, also known as metastasin, has long been regarded as a biological marker in tumor progression and metastasis in multiple solid cancers, but its clinical significance in acute myeloid leukemia (AML) has not been extensively studied.

Distinct genetic landscapes and their clinical implications in younger and older patients with myelodysplastic syndromes.

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.

Functional association of NR4A3 downregulation with impaired differentiation in myeloid leukemogenesis.

The coincident downregulation of NR4A1 and NR4A3 has been implicated in myeloid leukemogenesis, but it remains unknown how these two genes function in myeloid cells and how their combined downregulation promotes myeloid leukemogenesis. Since NR4A1 abrogation is thought to confer a survival and proliferation advantage to myeloid cells, we hypothesized that downregulation of NR4A3 may have a complementary effect on myeloid cell differentiation. First, we tested the association between differentiation status of leukemic cells and NR4A3 expression using two large clinical datasets from patients with different acute myeloid leukemia (AML) subtypes.

Signal peptide-CUB-EGF-like repeat-containing protein 1-promoted FLT3 signaling is critical for the initiation and maintenance of MLL-rearranged acute leukemia.

A hallmark of mixed lineage leukemia gene-rearranged (MLL-r) acute myeloid leukemia that offers an opportunity for targeted therapy is addiction to protein tyrosine kinase signaling. One such signal is the receptor tyrosine kinase Fms-like receptor tyrosine kinase 3 (FLT3) upregulated by cooperation of the transcription factors homeobox A9 (HOXA9) and Meis homeobox 1 (MEIS1). Signal peptide-CUB-EGF-like repeat-containing protein (SCUBE) family proteins have previously been shown to act as a co-receptor for augmenting signaling activity of a receptor tyrosine kinase (e.

Phosphoproteomics Reveals the Role of Constitutive KAP1 Phosphorylation by B-cell Receptor Signaling in Chronic Lymphocytic Leukemia.

Unlabelled: Application of B-cell receptor (BCR) pathway inhibitor ibrutinib for chronic lymphocytic leukemia (CLL) is a major breakthrough, yet the downstream effects following inhibition of BCR signaling and during relapse await further clarification. By comparative phosphoproteomic profiling of B cells from patients with CLL and healthy donors, as well as CLL B cells collected at multiple time points during the course of ibrutinib treatment, we provided the landscape of dysregulated phosphoproteome in CLL and its dynamic alterations associated with ibrutinib treatment. Particularly, differential phosphorylation events associated with several signaling pathways, including BCR pathway, were enriched in patient CLL cells.