myelodysplastic syndrome review

OBJECTIVES: VEXAS syndrome is an adult-onset autoinflammatory disease caused by a somatic pathogenic mutation in the UBA1 (ubiquitin-like modifier activating enzyme 1) gene. Patients present with rheumatologic manifestations and cytopenias and may have an increased predisposition to myelodysplastic syndrome (MDS) and plasma cell neoplasms. Prior studies have reported on the peripheral blood and bone marrow findings in patients with VEXAS syndrome. Due to the protean clinical presentation and lack of specificity of morphologic features (eg, vacuoles in early erythroid and granulocytic precursors), an optimal screening methodology to identify these patients in a timely fashion is desirable...

Azacitidine, a hypomethylating agent, has caused a paradigm shift in the outcomes of patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) who are not eligible for stem cell transplantation, particularly in combination with BCL2 and IDH inhibitors. Azacitidine and Azacitidine-based combinations have been widely considered a safe low-intensity therapy when compared to traditional conventional treatments. The development of lung toxicity from azacitidine is not a well-characterized adverse event...

Non-acute myeloid neoplasms (MNs) with NPM1 mutations ( NPM1 mut-MNs) pose a diagnostic and therapeutic dilemma, primarily manifesting as chronic myelomonocytic leukemia (CMML) and myelodysplastic syndromes (MDS). The classification and treatment approach for these conditions as acute myeloid leukemia (AML) are debated. We describe eight cases of atypical NPM1 mut-MNs from our institution and review the literature. We include a rare case of concurrent prostate carcinoma and MN consistent with chronic eosinophilic leukemia, progressing to myeloid sarcoma of the skin...

Myeloid neoplasms are clonal disorders that arise via acquisition of genetic mutations leading to excessive proliferation and defective differentiation. Mutational profiling is vital as it has implications on diagnosis, prognosis, and therapeutic decision making. Next generation sequencing (NGS) has become a mainstay in the evaluation of myeloid malignancies, as it enables efficient characterisation of multiple genetic changes. Herein the analytical validation of the 37-gene Archer VariantPlex Core Myeloid panel is reported, using 58 DNA specimens with 87 single nucleotide variants (SNV) and 23 insertions/deletions (INDEL)...

BACKGROUND: Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) present intricate challenges due to their diverse clinical manifestations and thrombotic complications. Thromboembolism (TE) incidence in newly diagnosed AML patients is noteworthy, with arterial TE linked to poorer overall survival. Ischemic strokes, although relatively low in prevalence, carry significant clinical implications. CASE DESCRIPTION: We report the case of an 84-year-old male with Type 2 Diabetes, Hypertension, and Chronic Kidney Disease, presenting with seizures, focal neurological deficits, and pancytopenia...

DDX41 is a DEAD-box helicase and is conserved across species. Mutations in DDX41 have been associated with myeloid neoplasms, including myelodysplastic syndrome and acute myeloid leukemia. Though its pathogenesis is not completely known, DDX41 has been shown to have many cellular roles, including in pre-mRNA splicing, innate immune sensing, ribosome biogenesis, translational regulation, and R-loop metabolism. In this review, we will summarize the latest understandings regarding the various roles of DDX41, as well as highlight challenges associated with drug development to target DDX41...

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive hematologic malignancy with poor outcomes. The World Health Organization (WHO) redefined BDCN as a distinct disease entity in 2016. BPDCN arises from plasmacytoid dendritic cells, manifesting primarily in the skin, bone marrow, and lymph nodes, occasionally involving the central nervous system (CNS). This presents challenges in diagnosis and treatment, with CNS involvement often overlooked in standard diagnostic workups due to BPDCN's rarity and patients often being neurologically asymptomatic at diagnosis...

Myelodysplastic syndrome (MDS) is a rare clonal hematopoietic disorder in children. The risk stratification system and treatment strategy for adults are unfit for children. The role of hypomethylating agents (HMAs) in higher-risk childhood MDS has not been identified. This study aimed to investigate the outcomes of hematopoietic stem cell transplantation (HSCT) in children with higher-risk MDS at one single center. A retrospective study was conducted in children with higher-risk MDS undergoing HSCT between September 2019 and March 2023 at Blood Diseases Hospital CAMS...

Hematopoietic cell transplantation (HCT) has evolved to an essential treatment in younger and more recently in elderly patients with myelodysplastic syndrome (MDS), the age group with the highest incidence. Less intense conditioning regimens and improvements in supportive therapy have reduced considerably transplant related mortality and in the same time increased the access to this curative treatment. Timing of HCT in the course of the disease assumes a crucial role. Detection of disease progression, geriatric assessment, comorbidity evaluation, and identification of transplant-specific risks are becoming increasingly important in this context...

Myeloid malignancies are clonal disorders of the progenitor cells or hematopoietic stem cells, including acute myeloid leukemia, myelodysplastic syndromes, myeloproliferative malignancies, and chronic myelomonocytic leukemia. Myeloid neoplastic cells affect the proliferation and differentiation of other hematopoietic lineages in the bone marrow and peripheral blood, leading to severe and life-threatening complications. Mesenchymal stromal cells (MSCs) residing in the bone marrow exert immunosuppressive functions by suppressing innate and adaptive immune systems, thus creating a supportive and tolerant microenvironment for myeloid malignancy progression...

In the intricate orchestration of the central dogma, pre-mRNA splicing plays a crucial role in the post-transcriptional process that transforms DNA into mature mRNA. Widely acknowledged as a pivotal RNA processing step, it significantly influences gene expression and alters the functionality of gene product proteins. While U2-dependent spliceosomes efficiently manage the removal of over 99% of introns, a distinct subset of essential genes undergo splicing with a different intron type, denoted as minor introns, using U12-dependent spliceosomes...

VEXAS (Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic) syndrome is a recently described autoinflammatory syndrome, mostly affecting men older than 50 years, caused by somatic mutation in the UBA1 gene, a X-linked gene involved in the activation of ubiquitin system. Patients present a broad spectrum of inflammatory manifestations (fever, neutrophilic dermatosis, chondritis, pulmonary infiltrates, ocular inflammation, venous thrombosis) and hematological involvement (macrocytic anemia, thrombocytopenia, vacuoles in myeloid and erythroid precursor cells, dysplastic bone marrow) that are responsible for a significant morbidity and mortality...

Allogeneic hematopoietic stem cell transplant (HSCT) is the only potentially curative option for patients with high-risk myelodysplastic syndromes (MDS). Advances in conditioning regimens and supportive measures have reduced treatment-related mortality and increased the role of transplantation, leading to more patients undergoing HSCT. However, post-transplant relapse of MDS remains a leading cause of morbidity and mortality for this procedure necessitating expert management and ongoing results analysis. In this article, we review treatment options and our institutional approaches to managing MDS relapse after HSCT using illustrative clinical cases that exemplify different clinical manifestations and management of relapse...

Inherited bone marrow failure syndromes and germline predisposition syndromes (IBMFS/GPS) are associated with increased risk for hematologic malignancies, particularly myeloid neoplasms, such as myelodysplastic neoplasms (MDS) and acute myeloid leukemia (AML). The diagnosis of MDS in these syndromes poses difficulty due to frequent bone marrow hypocellularity and the presence of some degree of dysplastic features related to the underlying germline defect causing abnormal maturation of one or more cell lines...

Vacuoles, E1-ubiquitin-activating enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome, caused by an acquired mutation in the ubiquitin-activating enzyme ubiquitin-like modifier activating enzyme 1 (UBA1), was discovered in 2020. Since then, many cases have been reported worldwide. Recently, we performed UBA1 genetic testing in suspected cases of VEXAS throughout Japan and investigated the clinical features of these cases. Most cases were elderly patients in their 70s with clinical features consistent with VEXAS syndrome, such as myelodysplastic syndrome, high-grade fever, skin rash, chondritis, and pulmonary infiltration...

OVERVIEW: Essential thrombocythemia is a Janus kinase 2 (JAK2) mutation-prevalent myeloproliferative neoplasm characterized by clonal thrombocytosis; clinical course is often indolent but might be interrupted by thrombotic or hemorrhagic complications, microcirculatory symptoms (e.g., headaches, lightheadedness, and acral paresthesias), and, less frequently, by disease transformation into myelofibrosis (MF) or acute myeloid leukemia. DIAGNOSIS: In addition to thrombocytosis (platelets ≥450 × 109 /L), formal diagnosis requires the exclusion of other myeloid neoplasms, including prefibrotic MF, polycythemia vera, chronic myeloid leukemia, and myelodysplastic syndromes with ring sideroblasts and thrombocytosis...

Invasive fungal diseases (IFDs) still represent a relevant cause of mortality in patients affected by hematological malignancies, especially acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) undergoing remission induction chemotherapy, and in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Mold-active antifungal prophylaxis (MAP) has been established as a standard of care. However, breakthrough IFDs (b-IFDs) have emerged as a significant issue, particularly invasive aspergillosis and non- Aspergillus invasive mold diseases...

Eosinophils in peripheral blood account for 0.3-5% of leukocytes, which is equivalent to 0.05-0.5 × 109 /L. A count above 0.5 × 109 /L is considered to indicate eosinophilia, while a count equal to or above 1.5 × 109 /L is defined as hypereosinophilia. In bone marrow aspirate, eosinophilia is considered when eosinophils make up more than 6% of the total nuclear cells. In daily clinical practice, the most common causes of reactive eosinophilia are non-hematologic, whether they are non-neoplastic (allergic diseases, drugs, infections, or immunological diseases) or neoplastic (solid tumors)...

Iron overload emerges as a serious complication in myelodysplastic syndromes (MDS), particularly associated with frequent transfusions during the course of the disease. The discovery and description of hepcidin's mechanisms of action have contributed to a deeper understanding of iron metabolism. The existing literature reports a potential role of hepcidin in MDS, yet these data are fragmented and presented in an unstructured, somewhat chaotic manner. Hence, to address the existing data, we performed a systematic review of observational studies examining hepcidin levels in MDS...

Escape from immune surveillance is a hallmark of cancer. Immune deregulation caused by intrinsic and extrinsic cellular factors, such as altered T cell functions, leads to immune exhaustion, loss of immune surveillance, and clonal proliferation of tumoral cells. The T cell immune system contributes to the pathogenesis, maintenance, and progression of myelodysplastic syndrome (MDS). Here, we comprehensively reviewed our current biological knowledge of the T cell compartment in MDS and recent advances in the development of immunotherapeutic strategies, such as immune checkpoint inhibitors and T cell- and antibody-based adoptive therapies, that hold promise to improve the outcome of MDS patients...