Megaloblastic anemia (MBA) is a reversible metabolic disorder that responds well to vitamin B12 supplementation. It contrasts with myelodysplastic syndrome (MDS), an irreversible neoplastic condition characterized by hematopoietic stem cell abnormalities. To date, no association has been identified between these two distinct etiologies, and they are considered independent diseases. However, despite their distinct classifications, both conditions present macrocytic anemia, similar bone marrow findings, and sometimes have common chromosomal abnormalities, which can lead to occasional misdiagnoses. Herein, we present a patient initially diagnosed with pernicious anemia (PA) who showed improvement with replacement therapy but subsequently became resistant to treatment and eventually developed MDS. Quantitative assessment of Wilm\'s tumor-1 (WT1) mRNA has emerged as a valuable tool for gauging MDS disease status and distinguishing it from related disorders, such as aplastic anemia. In our investigation of 30 patients with MBA, we explored WT1 mRNA expression. We observed its presence in 10 patients with PA, which suggests a potential link between PA and hematopoietic tumors.

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Etiological factors involved in myelodysplastic syndrome (MDS) include immunologic, oxidative stress and inflammatory factors, among others, and these are targets for microRNAs (miRNs). Here, we evaluated whether some miRNs may affect tumor development comparing untreated and 5-azacitidine (5-AZA) MDS-treated patients. Peripheral blood samples were collected from 20 controls and 24 MDS patients, and selected miRNs related to redox balance and inflammation (inflamma-miRs), including miR-18a, miR-21, miR-34a and miR-146a, were isolated and measured by quantitative real-time polymerase chain reaction (qRTPCR). A differential expression profile of miRNs was detected in untreated MDS patients and the 5-AZA group. Inflammation increases miRNs and, specifically, miR-18a, miR-21 and miR-34a were significantly overexpressed in untreated MDS, compared to controls. However, we did not observe any miRN profile alteration during the progression of the disease. On the other hand, 5-AZA treatment tends to restore miRN expression levels. Relating to prognostic risk factors, high-risk MDS groups (high Revised International Prognostic Scoring System (IPSS-R), high cytogenetic risk, high molecular risk (HMR) mutations) tended to be related with higher expression levels of miR-18a and miR-34a. Higher miRN expression is correlated with lower glutathione peroxidase activity, while they are related with a higher profile of pro-inflammatory cytokines (IL-2, IL-6, IL-8, TNF-α). Although our study was limited by the low number of MDS patients included, we identified miRN deregulation involved in MDS development that could regulate redox sensors and inflammatory responses. Finally, 5-AZA treatment is related with lower miRN expression levels in MDS patients.

Vitamin B12 deficiency is a common condition that is often asymptomatic, though in severe cases may cause megaloblastic anemia and even neurologic symptoms. Occasionally, the clinical presentation can include pancytopenia and thus mimic a more concerning myelodysplastic syndrome (MDS) until corrected by B12 supplementation. In this unusual case, we present a patient with B12 deficiency who presents with severe macrocytic anemia, neutropenia, lymphocytosis, and a bone marrow morphology consistent with MDS.

OBJECTIVE: Constitutional chromosomal aberrations are rare in hematologic malignancies and their pathogenetic role is mostly poorly understood. We present a comprehensive molecular characterization of a novel constitutional chromosomal translocation found in two siblings - sisters - diagnosed with myelodysplastic syndrome (MDS).
METHODS: Bone marrow and blood cells from the two patients were examined using G-banding, RNA sequencing, PCR, and Sanger sequencing.
RESULTS: We identified a balanced t(17;19)(q21;p13) translocation in both siblings\' bone marrow, blood cells, and phytohemagglutinin-stimulated lymphocytes. The translocation generated a MYO1F::WNK4 chimera on the der(19)t(17;19), encoding a chimeric serine/threonine kinase, and a VPS25::MYO1F on the der(17), potentially resulting in an aberrant VPS25 protein.
CONCLUSIONS: The t(17;19)(q21;p13) translocation found in the two sisters probably predisposed them to myelodysplasia. How the MYO1F::WNK4 and/or VPS25::MYO1F chimeras, perhaps especially MYO1F::WNK4 that encodes a chimeric serine/threonine kinase, played a role in MDS pathogenesis, remains incompletely understood.

Myelodysplastic syndrome (MDS) is a heterogeneous hematological condition associated with cytopenia, inadequate blood cell synthesis, and the risk of developing acute myeloid leukemia (AML). Patients are divided into risk groups according to the International Prognostic Scoring System (IPSS) to help direct therapy. Allogeneic stem cell transplantation, despite its limitations, is curative. Medical management, such as the use of lenalidomide, has potential benefits but can cause adverse effects that require dose regimen modification. Lenalidomide is approved for low-risk MDS with 5q deletion (5q- MDS). In this case study, a 79-year-old woman with 5q- MDS was switched from a daily regimen to an alternate-day lenalidomide dose schedule to achieve complete remission with fewer adverse effects. The management of hematological toxicity and the mechanisms of action of lenalidomide are discussed. We recommend individualized treatment strategies and additional research to improve MDS management.

Myelodysplastic syndrome (MDS) is characterized by failure to initiate hematopoiesis or impaired maturation of cells, often presenting with pancytopenias with or without associated fatigue, infections, or inappropriate bleeding and bruising. Karyotype analyses of MDS patients commonly show deletion of the q arm of chromosome 7, suggesting loss of this region is likely implicated in the insufficient hematopoiesis seen in MDS. The predisposition to deletion of 7q is commonly inherited, with clinical presentation in early childhood associated with pancytopenia or hematological malignancy. In this case, we present a 66-year-old female who was incidentally found to be pancytopenic in the emergency department while being evaluated for dyspnea, with a bone marrow biopsy later confirming a diagnosis of MDS with monosomy 7. Sporadic loss of 7q can occur at any stage in life without any family history of hematological disease. Our patient has no known personal or family history of MDS, with normal blood counts during hospitalization three years prior, suggesting de novo loss of 7q occurring at greater than 60 years of age.

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.
METHODS: 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. An unexpected diagnosis of AML or MDS emerged during the investigation. Despite interventions, the patient\'s condition deteriorated, leading to a fatal outcome weeks later.
CONCLUSIONS: This case underscores the intricate relationship between hematologic malignancies and ischemic stroke. The rarity of this complication emphasizes the importance of understanding the multifaceted mechanisms at play, including hyperleukocytosis, pro-inflammatory cytokine release, coagulation cascade activation, and direct interactions with endothelial cells. In our literature review, analysis of 15 cases, including ours, revealed a wide age range (3-87 years) and a gender bias towards females. AML diagnosis was predominant, with uniformly low platelet counts. Cortical infarctions, especially in the anterior circulation, were common. Hyperleukocytosis, disseminated intravascular coagulation (DIC), and fatal outcomes were observed in a subset of cases. Despite the grim statistics and often poor prognosis, the identification of specific risk factors, such as thrombocytopenia and cytogenetic abnormalities, offers avenues for targeted prevention and management.

UNASSIGNED: Without a definitive curative option available to many patients, learning to live with myelodysplastic syndrome (MDS) and manage symptoms effectively becomes a priority in their care. Anaemia is an almost universal feature of MDS. Individuals suffer differently and better individualisation of care is needed. Most MDS patient information offers scant appreciation for disease heterogeneity, variable response to treatment and each patient\'s likely trajectory.
UNASSIGNED: We undertook a two-part, online workshop to discuss what matters most to people living with MDS. Patients generated questions about their condition which they felt should be addressed by research or change how their care is delivered. Patients voted on the importance of each topic, creating a \"prioritised\" list of issues.
UNASSIGNED: Fourteen participants of varying age and experience took part raising 56 unique questions under the themes of: prognosis; end of life; treatment; supportive care; medical staff training; diagnosis and communication. These reflect the symptoms of MDS, improving quality of life (QoL) and communication.
UNASSIGNED: Although haemoglobin (Hb) levels have correlation to QoL, it is widely reported that other factors are important in determining QoL and need for transfusions varies despite stable Hb levels. We showed that Hb level and the need for transfusions is not comparable between different patients and even non-comparable over time meaning that the maximal benefit and timing of transfusions cannot be determined from Hb alone. This workshop highlighted patient dissatisfaction with the \"numbers-led\" approach and the need for an alternative method to determine when to transfuse.

The correct maintenance and differentiation of hematopoietic stem cells (HSC) in bone marrow is vital for the maintenance and operation of the human blood system. GATA2 plays a critical role in the maintenance of HSCs and the specification of HSCs into the different hematopoietic lineages, highlighted by the various defects observed in patients with heterozygous mutations in GATA2, resulting in cytopenias, bone marrow failure and increased chance of myeloid malignancy, termed GATA2 deficiency syndrome. Despite this, the mechanisms underlying GATA2 deficiency syndrome remain to be elucidated. The detailed description of how GATA2 regulates HSC maintenance and blood lineage determination is crucial to unravel the pathogenesis of GATA2 deficiency syndrome. In this review, we summarize current advances in elucidating the role of GATA2 in hematopoietic cell fate determination and discuss the challenges of modeling GATA2 deficiency syndrome.