Explore the vast range of titles available.

Introduction Activated PI3Kδ Syndrome (APDS) is a rare inborn error of immunity characterized by recurrent infections, lymphoproliferation, and autoimmunity. It results from mutations in the phosphoinositide 3-kinase delta (PI3Kδ) signalling pathway, leading to either gain-of-function (APDS1) or loss-of-function (APDS2) phenotypes. Clinical presentation ranges from asymptomatic to severe, depending on the underlying genetic defect. Malignancy, particularly lymphoma, represents the most frequent and life-threatening complication. Due to overlapping features with other primary immunodeficiencies, APDS is often misdiagnosed as combined immunodeficiency. Early molecular testing, particularly genetic analysis, is therefore crucial for accurate diagnosis. Although management remains complex and heterogeneous, there is growing interest in targeted approaches, particularly PI3Kδ-specific therapy. Case report We describe a 12-year-old boy with recurrent respiratory and ear infections since infancy, accompanied by persistent lymphadenopathy, hepatosplenomegaly, and thrombocytopenia. Initial immunological evaluation suggested combined immunodeficiency, and prophylactic antibiotics were initiated, but genetic testing was deferred due to mild clinical features and parental reluctance. Following multiple years of enduring symptoms, genetic investigation identified a PIK3CD mutation leading in a missense alteration p.Glu1021Lys, confirming APDS 1. The patient was subsequently commenced on immunoglobulin replacement therapy and consulted for consideration of immunosuppressive and targeted pathway blocker therapy. Conclusion This case highlights the diagnostic challenges of APDS, arising from both overlapping clinical features with other immunodeficiencies and external factors such as cost and parental decision-making. Early genetic testing facilitates accurate diagnosis, and timely recognition of APDS enables appropriate management, including immunosuppressive, targeted therapies and, in selected cases, potentially curative hematopoietic stem cell transplantation.

The dysregulation of non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), leads to the development and advancement of multiple myeloma (MM). miRNAs, in particular, are paramount in post-transcriptional gene regulation, promoting mRNA degradation and translational inhibition. As a result, miRNAs can serve as oncogenes or tumor suppressors depending on the target genes. In MM, miRNA disruption could result in abnormal gene expression responsible for cell growth, apoptosis, and other biological processes pertinent to cancer development. The dysregulated miRNAs inhibit the activity of tumor suppressor genes, contributing to disease progression. Nonetheless, several miRNAs are downregulated in MM and have been identified as gene regulators implicated in extracellular matrix remodeling and cell adhesion. miRNA depletion potentially facilitates the tumor advancement and resistance of therapeutic drugs. Additionally, lncRNAs are key regulators of numerous cellular processes, such as gene expression, chromatin remodeling, protein trafficking, and recently linked MM development. The lncRNAs are uniquely expressed and influence gene expression that supports MM growth, in addition to facilitating cellular proliferation and viability via multiple molecular pathways. miRNA and lncRNA alterations potentially result in anomalous gene expression and interfere with the regular functioning of MM. Thus, this review aims to highlight the dysregulation of these ncRNAs, which engender novel therapeutic modalities for the treatment of MM.

Randomized clinical trials have shown ixazomib, lenalidomide and dexamethasone (IRd) to be efficacious and safe in Asian patients with relapsed/refractory multiple myeloma (RRMM); however, real-world data are limited. The APEX study was a multicenter, observational cohort study of IRd conducted at 16 sites across South Korea, Malaysia, and Thailand. Overall, 104 patients treated with IRd during 2016–2023 were enrolled; data were collected by retrospective chart review and 6-month prospective follow-up. Median age at IRd initiation was 64.0 years. The primary endpoints of median time to next treatment (TTNT) and overall response rate (ORR) were 32.1 months and 72.1%, respectively (though ORR varied across countries). The secondary endpoint of median progression-free survival was 27.7 months, while median overall survival was not reached. Median TTNT and ORR were higher in elderly patients (≥65 and/or ≥70 years) than in the overall population. Adverse events occurred in 90.4% and serious adverse events occurred in 29.8% of all patients; common Grade ≥ 3 adverse drug reactions were pneumonia (9.6%), neutropenia (7.7%), and gastroenteritis (2.9%). This study demonstrated that IRd was safe and effective in real-world practice in Asia, including for elderly patients, and the results are aligned with TOURMALINE-MM1 and other real-world studies.

Background The acceptability and impact of mobile health (mHealth) applications on health outcomes in haemato-oncology remain unclear, particularly for patients undergoing long-term oral systematic anticancer therapy (SACT). Purpose This systematic review investigated the acceptability and efficacy of mHealth applications in facilitating self-management of oral SACT in patients with haematological malignancies. Methods We conducted a comprehensive search of five electronic databases, PubMed, PsycINFO, CINAHL, Cochrane Library, and Web of Science, until October 2024, and extracted data, including methodologies, application names, functionalities, and key results. This was followed by a narrative synthesis of quantitative outcomes, and a thematic analysis of qualitative data. Results Eight studies were included, comprising three qualitative studies, one randomised controlled trial, one non-randomised trial, and three mixed-method studies. mHealth applications for self-managing oral SACT exhibited acceptability, with usability and satisfaction ratings between 60% and 78%. Using the Normalisation Process Theory, four themes influencing acceptability were: (1) coherence – perceived benefits, (2) cognitive participation – barriers from technical issues, (3) collective action – burden from excessive notifications and inadequate support, and (4) reflexive monitoring – integration challenges in daily routine. Despite no major clinical or behavioural improvements, mHealth applications enhanced patient awareness of support, online health knowledge, and reduced daily life impact. Conclusion Fostering effective self-management of oral SACT in patients with haematological malignancies requires addressing issues such as application glitches, notification fatigue, and integration barriers to optimise these interventions. Future well-designed clinical trials are warranted to validate the impact of these applications on patient outcomes in cancer care.

Despite the excellent efficacy and improved clinical responses obtained with imatinib mesylate (IM), development of resistance in a significant proportion of chronic myeloid leukemia (CML) patients on IM therapy have emerged as a challenging problem in clinical practice. Resistance to imatinib can be due to heterogeneous array of factors involving BCR/ABL-dependent and BCR/ABL-independent pathways. Although BCR/ABL mutation is the major contributory factor for IM resistance, reduced bio-availability of IM in leukemic cells is also an important pharmacokinetic factor that contributes to development of resistance to IM in CML patients. The contribution of polymorphisms of the pharmacogenes in relation to IM disposition and treatment outcomes have been studied by various research groups in numerous population cohorts. However, the conclusions arising from these studies have been highly inconsistent. This review encompasses an updated insight into the impact of pharmacogenetic variability on treatment response of IM in CML patients.

Multiple myeloma (MM) is an incurable hematologic malignancy. Most MM patients are diagnosed at a late stage because the early symptoms of the disease can be uncertain and nonspecific, often resembling other, more common conditions. Additionally, MM patients are commonly associated with rapid relapse and an inevitable refractory phase. MM is characterized by the abnormal proliferation of monoclonal plasma cells in the bone marrow. During the progression of MM, massive genomic alterations occur that target multiple signaling pathways and are accompanied by a multistep process involving differentiation, proliferation, and invasion. Moreover, the transformation of healthy plasma cell biology into genetically heterogeneous MM clones is driven by a variety of post-translational protein modifications (PTMs), which has complicated the discovery of effective treatments. PTMs have been identified as the most promising candidates for biomarker detection, and further research has been recommended to develop promising surrogate markers. Proteomics research has begun in MM, and a comprehensive literature review is available. However, proteomics applications in MM have yet to make significant progress. Exploration of proteomic alterations in MM is worthwhile to improve understanding of the pathophysiology of MM and to search for new treatment targets. Proteomics studies using mass spectrometry (MS) in conjunction with robust bioinformatics tools are an excellent way to learn more about protein changes and modifications during disease progression MM. This article addresses in depth the proteomic changes associated with MM disease transformation.

Secondary acute myeloid leukemia (sAML) typically arises from a prior myeloid malignancy or as a complication of cytotoxic therapy for other cancers. Rarely, it may develop without antecedent treatment, particularly in lymphoid malignancies. We report an unusual case of sAML in a treatment‐naïve patient previously diagnosed with primary testicular diffuse large B‐cell lymphoma (DLBCL). A 58‐year‐old male initially presented with Stage 1E primary testicular DLBCL and declined recommended treatment. Five years later, he developed symptoms and laboratory features of acute myeloid leukemia (AML), confirmed as monocytic subtype (M5) via immunophenotyping. Despite planned hypomethylating agent‐based therapy, he succumbed during bridging treatment. This case highlights the diagnostic importance of immunophenotyping and an uncommon clinical trajectory from untreated lymphoid malignancy to sAML.

Multiple myeloma (MM) is an exceptionally complicated and heterogeneous disease that is caused by the abnormal proliferation of malignant monoclonal plasma cells initiated in the bone marrow. In disease progression, a multistep process including differentiation, proliferation, and invasion is involved. Despite great improvement in treatment outcomes in recent years due to the substantial discovery of novel therapeutic drugs, MM is still regarded as an incurable disease. Patients with MM are afflicted by confronting remission periods accompanied by relapse or progression outcomes, which inevitably progress to the refractory stage. In this regard, MM may need new medications or modifications in therapeutic strategies to overcome resistance. A variety of genetic abnormalities (e.g., point mutations, translocations, and deletions) and epigenetic changes (e.g., DNA methylation, histone modification, and non-coding RNA) contribute to the pathogenesis and development of MM. Here, we review the significant roles of epigenetic mechanisms in the development and progression of MM. We also highlight epigenetic pathways as potential novel treatment avenues for MM, including their interplay, use of epigenetic inhibitors, and major involvement in immuno-oncology.

Bacground: The pathogenesis of systemic mastocytosis with associated haematological neoplasm (SMAHN) is not well understood. Both diagnoses heavily rely on morphological evaluation because SM is rarely suspected in clinical practise. Objective: This case highlighted a possible delay in diagnosis due to underlying conditions or diseases. Case Report: We present a case of a patient with acute myeloid leukaemia (AML), acute myelomonocytic subtype, and concurrent mastocytosis according to World Health Organization (WHO) classification. Due to an extensive accumulation of AML blast cells that obscured the mast cell infiltrates, mastocytosis was not evident at the first diagnosis. Discussion and conclusion: The diagnosis, in this case, was established only in the third bone marrow biopsy after chemotherapy. A high index of suspicion with morphological and immunohistochemical evaluations for neoplastic mast cell populations should be considered. The optimal treatment approach should be chosen based on these two disease entities. Bangladesh Journal of Medical Science Vol. 22 No. 04 October’23 Page : 937-941

Bartonella henselae is a recognized cause of neuroretinitis in cat scratch disease. Meanwhile, polyneuropathy, organomegaly, endocrinopathy monoclonal gammopathy, skin changes (POEMS) syndrome with Castleman disease (evidence of lymph node hyperplasia), is a chronic debilitating condition that predisposes to various superimposed infections. B. henselae neuroretinitis implicated in POEMS syndrome has not been reported previously. A 34-year-old asymptomatic man was referred for an eye assessment. Examination showed visual acuity of 6/18 in the right eye and 6/24 in the left eye. On fundus examination, both eyes exhibited typical features of neuroretinitis (optic disc swelling and incomplete macular star). There was otherwise no vitritis or chorioretinitis. Serology for B. henselae revealed high immunoglobulin M (IgM) titer (1:96) indicative of acute disease, and positive immunoglobulin G (IgG) (1:156). He was treated with oral azithromycin for 6 weeks and a short course of oral prednisolone. Subsequently, the visual acuity in both eyes improved with resolution of macular star. However, both optic discs remained swollen. Keywords: Bartonella henselae neuroretinitis, POEMS syndrome, bilateral disc swelling