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Sobrecrecimiento Gingival , Leucemia Monocítica Aguda , Humanos , Masculino , Persona de Mediana Edad , Sobrecrecimiento Gingival/diagnóstico , Sobrecrecimiento Gingival/inducido químicamente , Sobrecrecimiento Gingival/etiología , Leucemia Monocítica Aguda/diagnóstico , Leucemia Monocítica Aguda/complicacionesRESUMEN
Wogonin is a natural flavone compound from the plant Scutellaria baicalensis, which has a variety of pharmacological activities such as anti-cancer, anti-virus, anti-inflammatory, and immune regulation. However, the potential mechanism of wogonin remains unknown. This study was to confirm the molecular mechanism of wogonin for acute monocytic leukemia treatment, known as AML-M5. The potential action targets between wogonin and acute monocytic leukemia were predicted from databases. The compound-target-pathway network and protein-protein interaction network (PPI) were constructed. The enrichment analysis of related targets and molecular docking were performed. The network pharmacological results of wogonin for AML-M5 treatment were verified using the THP-1 cell line. 71 target genes of wogonin associated with AML-M5 were found. The key genes TP53, SRC, AKT1, RELA, HSP90AA1, JUN, PIK3R1, and CCND1 were preliminarily found to be the potential central targets of wogonin for AML-M5 treatment. The PPI network analysis, GO analysis and KEGG pathway enrichment analysis demonstrated that the PI3K/AKT signaling pathway was the significant pathway in the wogonin for AML-M5 treatment. The antiproliferative effects of wogonin on THP-1 cells of AML-M5 presented a dose-dependent and time-dependent manner, inducing apoptosis, blocking the cell cycle at the G2/M phase, decreasing the expressions of CCND1, CDK2, and CyclinA2 mRNA, as well as AKT and p-AKT proteins. The mechanisms of wogonin on AML-M5 treatment may be associated with inhibiting cell proliferation and regulating the cell cycle via the PI3K/AKT signaling pathway.
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Flavanonas , Leucemia Monocítica Aguda , Simulación del Acoplamiento Molecular , Farmacología en Red , Mapas de Interacción de Proteínas , Flavanonas/farmacología , Humanos , Leucemia Monocítica Aguda/tratamiento farmacológico , Leucemia Monocítica Aguda/metabolismo , Leucemia Monocítica Aguda/patología , Mapas de Interacción de Proteínas/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células THP-1 , Línea Celular Tumoral , Apoptosis/efectos de los fármacosRESUMEN
Cytophagic histiocytic panniculitis (CHP) is associated with a number of systemic conditions and is characterized by the presence of benign phagocytic histiocytes ("bean bag cells"), including phagocytosed erythrocytes, leukocytes, and platelets. We describe a case of a 72-year-old female who presented with a papular eruption that clinically mimicked pityriasis lichenoides et varioliformis acuta (PLEVA). Given that her skin biopsy had multiple features concerning PLEVA, this diagnosis was classified as a superficial pityriasis lichenoides-like variant of CHP. The histopathologic presence of cytophagic histiocytosis prompted workup for a systemic malignancy, leading to a diagnosis of underlying acute monocytic leukemia of myeloid lineage.
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Paniculitis , Humanos , Femenino , Anciano , Paniculitis/patología , Paniculitis/diagnóstico , Histiocitos/patología , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/diagnóstico , Leucemia Monocítica Aguda/patología , Leucemia Monocítica Aguda/diagnóstico , Diagnóstico Diferencial , Diferenciación Celular , Monocitos/patologíaRESUMEN
The clinical treatment of human acute myeloid leukemia (AML) is rapidly progressing from chemotherapy to targeted therapies led by the BCL-2 inhibitor venetoclax (VEN). Despite its unprecedented success, VEN still encounters clinical resistance. Thus, uncovering the biological vulnerability of VEN-resistant AML disease and identifying effective therapies to treat them are urgently needed. We have previously demonstrated that iron oxide nanozymes (IONE) are capable of overcoming chemoresistance in AML. The current study reports a new activity of IONE in overcoming VEN resistance. Specifically, we revealed an aberrant redox balance with excessive intracellular reactive oxygen species (ROS) in VEN-resistant monocytic AML. Treatment with IONE potently induced ROS-dependent cell death in monocytic AML in both cell lines and primary AML models. In primary AML with developmental heterogeneity containing primitive and monocytic subpopulations, IONE selectively eradicated the VEN-resistant ROS-high monocytic subpopulation, successfully resolving the challenge of developmental heterogeneity faced by VEN. Overall, our study revealed an aberrant redox balance as a therapeutic target for monocytic AML and identified a candidate IONE that could selectively and potently eradicate VEN-resistant monocytic disease.
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Antineoplásicos , Compuestos Bicíclicos Heterocíclicos con Puentes , Resistencia a Antineoplásicos , Especies Reactivas de Oxígeno , Sulfonamidas , Humanos , Sulfonamidas/farmacología , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Resistencia a Antineoplásicos/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Leucemia Monocítica Aguda/tratamiento farmacológico , Leucemia Monocítica Aguda/metabolismo , Leucemia Monocítica Aguda/patología , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patología , Compuestos Férricos/farmacologíaRESUMEN
BACKGROUND: Lysine [K] methyltransferase 2A (KMT2A, previously known as MLL) gene rearrangements are common in acute leukemias of various lineages and are associated with features such as chemotherapy resistance and rapid relapse. KMT2A::CBL is a rare fusion of unknown pathogenesis generated by a unique interstitial deletion of chromosome 11 that has been reported across a wide age range in both acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) patients. The leukemogenic effect of the KMT2A::CBL rearrangement and its association with clinical prognosis have not been well clarified. METHODS AND RESULTS: We report the case of a 64-year-old female who was diagnosed with acute monoblastic leukemia (M5a) and who acquired the rare KMT2A::CBL fusion. The patient received multiple cycles of therapy but did not achieve remission and eventually succumbed to severe infection and disease progression. Additionally, we characterized the predicted KMT2A-CBL protein structure in this case to reveal the underlying leukemogenic mechanisms and summarized reported cases of hematological malignancies with KMT2A::CBL fusion to investigate the correlation of gene rearrangements with clinical outcomes. CONCLUSIONS: This report provides novel insights into the leukemogenic potential of the KMT2A::CBL rearrangement and the correlation between gene rearrangements and clinical outcomes.
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N-Metiltransferasa de Histona-Lisina , Leucemia Monocítica Aguda , Proteína de la Leucemia Mieloide-Linfoide , Proteínas Proto-Oncogénicas c-cbl , Femenino , Humanos , Persona de Mediana Edad , Progresión de la Enfermedad , Reordenamiento Génico/genética , Leucemia Monocítica Aguda/genética , Leucemia Monocítica Aguda/patología , N-Metiltransferasa de Histona-Lisina/genética , Proteína de la Leucemia Mieloide-Linfoide/genética , Proteínas Proto-Oncogénicas c-cbl/genéticaRESUMEN
A model construction of systemic acute leukemia is challenging. Herein, we established a systemic leukemia mouse model using highly immunodeficient NPG mice without any immunosuppressive treatments. NPG mice received tail intravenous injection of SHI-1 cells at the concentration of 1×107 cells (group A) or 5×107 cells (group B) and randomly sacrificed each seven days post-inoculation. Tumor development was monitored using nested-PCR, peripheral blood-smear analysis, flow cytometry, pathological examinations, and immunohistochemistry. The median survival of mice in groups A and B were 33.0 and 30.0 days, respectively. Blast cells in peripheral blood appeared on day 14 in group B, and on day 21 in group A. In addition, SHI-1 cell specific MLL-AF6 mRNA was detected in both spleen and bone marrow on day 14 post-inoculation. 21 days after inoculation, we observed human CD45+CD33+ cells with an SH-1-immunophenotype in the peripheral blood, spleen, and bone marrow, as well as solid neoplasms in multiple organs. Moreover, the histologically infiltrated leukemic cells expressed CD45. In conclusion, the current study demonstrated the normal growth of SHI-1 cells in the NPG mice without immunosuppression, which caused systemic leukemia similar to that observed in acute leukemia patients. We developed an efficient and reproducible model to study leukemia pathogenesis and progression.
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Modelos Animales de Enfermedad , Leucemia Monocítica Aguda , Animales , Ratones , Leucemia Monocítica Aguda/patología , Leucemia Monocítica Aguda/genética , Humanos , Línea Celular Tumoral , Infiltración Leucémica/patologíaRESUMEN
BACKGROUND: Leukemia cutis (LC) is an extramedullary acute myeloid leukemia (AML) infiltrate. No previous study has described the clinical characteristics and outcomes of Thai patients diagnosed with AML with LC. MATERIALS AND METHODS: We conducted a 7-year retrospective case-control study on Thai AML patients at Siriraj Hospital from November 2013 to July 2020. Patients were divided into LC and non-LC groups. Initial clinical presentations and laboratory findings were examined to identify LC-associated factors. Overall survival (OS) and relapse-free survival (RFS) were assessed. Pathological tissues underwent re-evaluation to validate the LC diagnoses. RESULTS: The study included 159 patients in a 2:1 ratio (106 non-LC and 53 LC). The LC group had a mean ± SD age of 54.3 ± 15.5 years; females were predominant. Three-fifths of the LC patients had intermediate-risk cytogenetics; 20.4% had an adverse risk, and 10.2% had a favorable risk. Most were classified as AML-M4 and AML-M5. Leukemic nodules were the primary finding in 58.5% of the cases, mainly on the legs. In the multivariate analysis of predictive factors associated with LC, organomegalies, specifically hepatomegaly, and lymphadenopathy, remained significant factors associated with LC [OR 4.45 (95%CI 1.20, 16.50); p = 0.026 and OR 5.48 (95%CI 1.65, 18.20); p = 0.005], respectively. The LC group demonstrated a significantly reduced OS (log-rank test p = 0.002) (median OS of 8.6 months vs. 32.4 months). RFS was considerably lower in the LC group (log-rank test p = 0.001) (median duration of 10.3 months vs. 24.4 months in the non-LC). CONCLUSIONS: AML patients who developed LC tended to experience notably poorer prognoses. Therefore, it is imperative to consider aggressive treatment options for such individuals. The presence of organomegalies in AML patients serves as a strong predictor of the possible occurrence of LC when accompanied by skin lesions.
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Leucemia Monocítica Aguda , Leucemia Mieloide Aguda , Neoplasias Cutáneas , Femenino , Humanos , Adulto , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Estudios de Casos y Controles , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/patología , Neoplasias Cutáneas/complicaciones , Recurrencia , PronósticoRESUMEN
ABSTRACT: We show that red cell exchange (RCE) treats hyperleukocytosis in acute leukemia. RCE provided similar leukoreduction to standard therapeutic leukoreduction and could be superior in patients with severe anemia or monocytic leukemias or when requiring rapid treatment.
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Leucemia Monocítica Aguda , Leucemia Mieloide Aguda , Leucostasis , Adulto , Humanos , Leucostasis/terapia , Leucemia Mieloide Aguda/terapia , Leucemia Monocítica Aguda/terapia , Enfermedad Aguda , Leucaféresis , Leucocitosis/terapiaRESUMEN
The human microbiota produces metabolites that can enter the bloodstream and exert systemic effects on various functions in both healthy and pathological states. We have studied the participation of microbiota-related metabolites in bacterial infection by examining their influence on the activity of cyclooxygenase (COX) as a key enzyme of inflammation. The influence of aromatic microbial metabolites, derivatives of phenylalanine (phenylpropionic acid, PPA), tyrosine (4-hydroxyphenyllactic acid, HPLA), and tryptophan (indolacetic acids, IAA), the concentrations of which in the blood change notably during sepsis, was evaluated. Also, the effect of itaconic acid (ITA) was studied, which is formed in macrophages under the action of bacterial lipopolysaccharides (LPS) and appears in the blood in the early stages of infection. Metabiotic acetyl phosphate (AcP) as a strong acetylating agent was also tested. The activity of COX was measured via the TMPD oxidation colorimetric assay using the commercial pure enzyme, cultured healthy monocytes, and the human acute monocytic leukemia cell line THP-1. All metabolites in the concentration range of 100-500 µM lowered the activity of COX. The most pronounced inhibition was observed on the commercial pure enzyme, reaching up to 40% in the presence of AcP and 20-30% in the presence of the other metabolites. On cell lysates, the effect of metabolites was preserved, although it significantly decreased, probably due to their interaction with other targets subject to redox-dependent and acetylation processes. The possible contribution of the redox-dependent action of microbial metabolites was confirmed by assessing the activity of the enzyme in the presence of thiol reagents and in model conditions, when the COX-formed peroxy intermediate was replaced with tert-butyl hydroperoxide (TBH). The data show the involvement of the microbial metabolites in the regulation of COX activity, probably due to their influence on the peroxidase activity of the enzyme.
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Leucemia Monocítica Aguda , Microbiota , Sepsis , Humanos , Monocitos/metabolismo , Ciclooxigenasa 2/metabolismo , Ciclooxigenasa 1/metabolismo , Sepsis/metabolismo , Antioxidantes/farmacología , Peroxidasas/metabolismo , Lipopolisacáridos/farmacología , Lipopolisacáridos/metabolismoRESUMEN
Cold atmospheric plasma (CAP) has been studied and clinically applied to treat chronic wounds, cancer, periodontitis, and other diseases. CAP exerts cytotoxic, bactericidal, cell-proliferative, and anti-inflammatory effects on living tissues by generating reactive species. Therefore, CAP holds promise as a treatment for diseases involving chronic inflammation and bacterial infections. However, the cellular mechanisms underlying these anti-inflammatory effects of CAP are still unclear. Thus, this study aimed to elucidate the anti-inflammatory mechanisms of CAP in vitro. The human acute monocytic leukemia cell line, THP-1, was stimulated with lipopolysaccharide and irradiated with CAP, and the cytotoxic effects of CAP were evaluated. Time-course differentiation of gene expression was analyzed, and key transcription factors were identified via transcriptome analysis. Additionally, the nuclear localization of the CAP-induced transcription factor was examined using western blotting. The results indicated that CAP showed no cytotoxic effects after less than 70 s of irradiation and significantly inhibited interleukin 6 (IL6) expression after more than 40 s of irradiation. Transcriptome analysis revealed many differentially expressed genes (DEGs) following CAP irradiation at all time points. Cluster analysis classified the DEGs into four distinct groups, each with time-dependent characteristics. Gene ontology and gene set enrichment analyses revealed CAP-induced suppression of IL6 production, other inflammatory responses, and the expression of genes related to major histocompatibility complex (MHC) class II. Transcription factor analysis suggested that nuclear factor erythroid 2-related factor 2 (NRF2), which suppresses intracellular oxidative stress, is the most activated transcription factor. Contrarily, regulatory factor X5, which regulates MHC class II expression, is the most suppressed transcription factor. Western blotting revealed the nuclear localization of NRF2 following CAP irradiation. These data suggest that CAP suppresses the inflammatory response, possibly by promoting NRF2 nuclear translocation.
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Leucemia Monocítica Aguda , Gases em Plasma , Humanos , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Células THP-1 , Gases em Plasma/farmacología , Interleucina-6 , Antiinflamatorios/farmacología , Línea Celular , LipopolisacáridosRESUMEN
Adoptive transfer of cultured BMSCs was shown to be immune-suppressive in various inflammatory settings. Many factors play a role in the process, but no master regulator of BMSC-driven immunomodulation was identified. Consequently, an assay that might predict BMSC product efficacy is still unavailable. Below, we show that BMSC donor variability can be monitored by IL-10 production of monocytes/macrophages using THP-1 cells (immortalized monocytic leukemia cells) co-cultured with BMSCs. Using a mixed lymphocyte reaction (MLR) assay, we also compared the ability of the different donor BMSCs to suppress T-cell proliferation, another measure of their immune-suppressive ability. We found that the BMSCs from a donor that induced the most IL-10 production were also the most efficient in suppressing T-cell proliferation. Transcriptome studies showed that the most potent BMSC batch also had higher expression of several known key immunomodulatory molecules such as hepatocyte growth factor (HGF), PDL1, and numerous members of the PGE2 pathway, including PTGS1 and TLR4. Multiplex ELISA experiments revealed higher expression of HGF and IL6 by the most potent BMSC donor. Based on these findings, we propose that THP-1 cells may be used to assess BMSC immunosuppressive activity as a product characterization assay.
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Médula Ósea , Leucemia Monocítica Aguda , Humanos , Proyectos Piloto , Interleucina-10 , Línea Celular , Células del EstromaRESUMEN
BACKGROUND: Acute myeloid leukemia (AML) and hyperleukocytosis have an unfavorable prognosis, but the impact of hyperleukocytosis on the prognosis of pediatric AML remains uncertain. We investigated the clinical characteristics and prognosis of pediatric AML with hyperleukocytosis, defined as WBC ≥ 50 × 109/L. METHODS: A total of 132 patients with newly diagnosed childhood AML with hyperleukocytosis were consecutively enrolled at our center from September 2009 to August 2021 to investigate prognostic factors and clinical outcomes. RESULTS: Hyperleukocytosis occurred in 27.4% of AML patients. Pediatric patients with hyperleukocytosis had similar CR and OS rates to those without hyperleukocytosis, but had a lower EFS rate. In our study, rates of CR1, mortality, relapsed/refractory disease, and HSCT were comparable between AML patients with WBC counts of 50-100 × 109/L and ≥ 100 × 109/L. AML patients with a WBC count of 50-100 × 109/L had a similar 5-year OS rate to patients with a WBC count ≥ 100 × 109/L (74.6% vs. 75.4%, P = 0.921). Among all patients with hyperleukocytosis, the FAB M5 subtype was associated with significantly inferior survival, and the prognosis of CBF-AML was good. CONCLUSIONS: Pediatric AML patients with hyperleukocytosis have the similar prognosis regardless of whether their WBC count is 50-100 × 109/L or ≥ 100 × 109/L.
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Leucemia Monocítica Aguda , Leucemia Mieloide Aguda , Humanos , Niño , Leucocitosis , Recuento de Leucocitos , Pronóstico , Leucemia Monocítica Aguda/complicaciones , Estudios RetrospectivosRESUMEN
Leukemia cutis is a comprehensive terminology for dermal manifestations of any type of leukemia either with accompanied or antecedent blood or bone marrow involvement. Although both myeloid and lymphoid neoplastic leukocytes can infiltrate the skin, the frequency is higher among children with congenital myeloid leukemia. However, the underlying pathogenesis of dermal tropism is not yet established. Clinical manifestation varies regarding appearance, site, and numbers. Skin biopsy is essential for the early establishment of the diagnosis and to guide for further testing and categorical management. We report the case of acute myeloid leukemia-cutis in a 22-year-old female where cutaneous manifestation preceded the hematological diagnosis of systemic leukemia.
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Leucemia Monocítica Aguda , Leucemia Mieloide Aguda , Neoplasias Cutáneas , Femenino , Niño , Humanos , Adulto Joven , Adulto , Leucemia Monocítica Aguda/complicaciones , Leucemia Monocítica Aguda/diagnóstico , Leucemia Monocítica Aguda/patología , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patología , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/patología , Piel/patología , BiopsiaRESUMEN
Acute monocytic leukemia is a type of myeloid leukemia that develops in monocytes. The current clinical therapies for leukemia are unsatisfactory due to their side effects and nonspecificity toward target cells. Some lectins display antitumor activity and may specifically recognize cancer cells by binding to carbohydrate structures on their surface. Therefore, this study evaluated the response of the human monocytic leukemia cell lines THP-1 to the Olneya tesota PF2 lectin. The induction of apoptosis and reactive oxygen species production in PF2-treated cells was evaluated by flow cytometry, and the lectin-THP-1â cell interaction and mitochondrial membrane potential were evaluated by confocal fluorescence microscopy. PF2 genotoxicity was evaluated by DNA fragmentation analysis via gel electrophoresis. The results showed that PF2 binds to THP-1 cells, triggers apoptosis and DNA degradation, changes the mitochondrial membrane potential, and increases reactive oxygen species levels in PF2-treated THP-1 cells. These results suggest the potential use of PF2 for developing alternative anticancer treatments with enhanced specificity.
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Lectinas , Leucemia Monocítica Aguda , Humanos , Lectinas/farmacología , Lectinas/metabolismo , Leucemia Monocítica Aguda/tratamiento farmacológico , Especies Reactivas de Oxígeno/metabolismo , Apoptosis/fisiología , Células THP-1RESUMEN
Acute myeloid leukemia (AML) is known as one of the subsequent malignant neoplasms that can develop after cancer treatment, but it is difficult to distinguish from relapse when the preceding cancer is leukemia. We report a 2-year-old boy who developed acute megakaryoblastic leukemia (AMKL, French-American-British classification [FAB]: M7) at 18 months of age and achieved complete remission with multi-agent chemotherapy without hematopoietic stem cell transplantation. Nine months after diagnosis and 4 months after completing treatment for AMKL, he developed acute monocytic leukemia (AMoL) with the KMT2A::LASP1 chimeric gene (FAB: M5b). The second complete remission was achieved using multi-agent chemotherapy and he underwent cord blood transplantation 4 months after AMoL was diagnosed. He is currently alive and disease free at 39 and 48 months since his AMoL and AMKL diagnoses, respectively. Retrospective analysis revealed that the KMT2A::LASP1 chimeric gene was detected 4 months after diagnosis of AMKL. Common somatic mutations were not detected in AMKL or AMoL and no germline pathogenic variants were detected. Since the patient's AMoL was different from his primary leukemia of AMKL in terms of morphological, genomic, and molecular analysis, we concluded that he developed a subsequent leukemia rather than a relapse of his primary leukemia.
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Leucemia Megacarioblástica Aguda , Leucemia Monocítica Aguda , Preescolar , Humanos , Masculino , Proteínas Adaptadoras Transductoras de Señales , Proteínas del Citoesqueleto , Leucemia Megacarioblástica Aguda/diagnóstico , Leucemia Megacarioblástica Aguda/genética , Leucemia Megacarioblástica Aguda/terapia , Leucemia Monocítica Aguda/diagnóstico , Leucemia Monocítica Aguda/genética , Leucemia Monocítica Aguda/terapia , Proteínas con Dominio LIM , Recurrencia , Inducción de Remisión , Estudios Retrospectivos , N-Metiltransferasa de Histona-Lisina/genética , Proteínas de Fusión Oncogénica/genéticaRESUMEN
BACKGROUND Refractory hypokalemia has been rarely demonstrated in patients with acute monocytic leukemia (AMoL). Hypokalemia develops in these patients owing to renal tubular dysfunction, secondary to lysozyme enzymes that are released by monocytes in AMoL. Additionally, renin-like substances are produced from monocytes and can lead to hypokalemia and metabolic alkalosis. There is also an entity called spurious hypokalemia, in which high numbers of metabolically active cells in blood samples increase sodium-potassium ATPase activity, resulting in influx of potassium. Additional research is warranted regarding this specific demographic to create standardized treatment approaches to electrolyte repletion. CASE REPORT In this case report, we demonstrate a rare case of an 82-year-old woman with AMoL, complicated by refractory hypokalemia, who presented with concerns of fatigue. The patient's initial laboratory results were significant for leukocytosis with monocytosis and severe hypokalemia. Refractory hypokalemia was noted, despite administration of aggressive repletions. During her hospitalization, AMoL was diagnosed and an extensive workup was performed to evaluate the underlying cause of hypokalemia. Ultimately, the patient died on day 4 of hospitalization. We describe the correlation between severe refractory hypokalemia and leukocytosis and provide a literature review of multiple etiologies of refractory hypokalemia in patients with AMoL. CONCLUSIONS We evaluated the numerous pathophysiologic mechanisms responsible for refractory hypokalemia in patients with AMoL. Our therapeutic outcomes were limited owing to the patient's early death. It is of high importance to evaluate the underlying cause of hypokalemia in these patients and to treat accordingly with caution.
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Hipopotasemia , Leucemia Monocítica Aguda , Anciano de 80 o más Años , Femenino , Humanos , Hipopotasemia/complicaciones , Leucemia Monocítica Aguda/complicaciones , Leucocitosis/complicaciones , PotasioRESUMEN
The cellkilling potential of most chemotherapeutic agents is enhanced by a temperature elevation. Isofraxidin (IF) is a coumarin compound widely found in plants, such as the Umbelliferae or Chloranthaceae families. IF induces anticancer effects in lung and colorectal cancer. To the best of our knowledge, the combined effects of hyperthermia (HT) and IF on heatinduced apoptosis have not been reported. Acute monocytic leukemia U937 cells were exposed to HT with or without IF pretreatment. Apoptosis was measured by Annexin VFITC/PI double staining assay using flow cytometry and cell viability was observed by cell counting kit assay, DNA fragmentation. The mechanism involved in the combination was explored by measuring changes in the mitochondrial membrane potential, (MMP), intracellular ROS generation, expression of apoptosis related protein, and intracellular calcium ion level. It was demonstrated that IF enhanced HTinduced apoptosis in U937 cells. The results demonstrated that combined treatment enhanced mitochondrial membrane potential loss and transient superoxide generation increased protein expression levels of caspase3, caspase8 and phosphorylatedJNK and intracellular calcium levels. Moreover, the role of caspases and JNK was confirmed using a pan caspase inhibitor (zVADFMK) and JNK inhibitor (SP600125) in U937 cells. Collectively, the data demonstrated that IF enhanced HTinduced apoptosis via a reactive oxygen species mediated mitochondria/caspasedependent pathway in U937 cells.
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Hipertermia Inducida , Leucemia Monocítica Aguda , Humanos , Células U937 , Calcio/metabolismo , Apoptosis , Cumarinas/farmacología , Caspasas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Oxidación-Reducción , Potencial de la Membrana MitocondrialRESUMEN
BACKGROUND: Ophthalmic manifestations are common in patients with leukemia, developing in nearly 50% of cases. Intracranial hemorrhage is another potentially fatal complication of leukemia. In this case report, we aim to present a challenging case that involves both ophthalmic and intracranial manifestations in an individual with acute monocytic leukemia. CASE PRESENTATION: A 36-year-old Persian male presented to the emergency room with complaints of fever, headache, and bilateral blurred vision. The patient had been diagnosed with acute monocytic leukemia 3 months prior and had undergone four sessions of induction chemotherapy, the last of which was 10 days prior to admission. The patient was admitted to the internal medicine service, and initial lab studies confirmed pancytopenia, including severe neutropenia, anemia, and thrombocytopenia. Subarachnoid hemorrhage in the left frontal lobe was detected through spiral brain computed tomography scan. Ophthalmic examination revealed visual acuity of light perception in the right eye and 3-m finger count in the left eye. Fundus examination revealed bilateral peripapillary subhyaloid and intraretinal hemorrhages, confirming leukemic retinopathy. The patient showed significant improvement in visual acuity and hemorrhage resolution through conservative treatment and regular follow-ups after 3 months. CONCLUSION: Simultaneous subarachnoid hemorrhage and bilateral subhyaloid hemorrhages seemed to have occurred as a result of pancytopenia. Management approach of ophthalmic manifestations of leukemia involves interdisciplinary cooperation and should be individualized on the basis of the patients' underlying medical condition.