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1.
Ultrastruct Pathol ; 48(3): 221-233, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38619116

RESUMO

The endoplasmic reticulum(ER)is the largest membranous network serving as a region for protein, lipid and steroid synthesis, transport and storage. Detailed information about ER-cisternae, ER-tubules and rough endoplasmic reticulum (rER) is scarce in human blood cells. This study describes a series of giant inclusions and Auer bodies in promyeloblasts in six patients with acute promyelocytic leukemia (APL), by light microscopy, transmission electron microscopy (TEM) and cytochemical stains. TEM revealed that giant inclusions and pro-Auer bodies were associated with rER and surrounded by tubular structures composed of degenerated or redundant membrane in promyeloblasts, which corresponded with elements of the ER system. This paper reveals that in the promyeloblasts of APL, ER is the source of and transforms progressively into giant inclusions and Auer bodies.


Assuntos
Retículo Endoplasmático , Corpos de Inclusão , Leucemia Promielocítica Aguda , Microscopia Eletrônica de Transmissão , Humanos , Leucemia Promielocítica Aguda/patologia , Corpos de Inclusão/ultraestrutura , Masculino , Feminino , Retículo Endoplasmático/ultraestrutura , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Adolescente , Células Precursoras de Granulócitos/ultraestrutura , Células Precursoras de Granulócitos/patologia
2.
Int J Mol Sci ; 25(4)2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38396817

RESUMO

Acute myeloid leukemia (AML) is an aggressive malignancy characterized by rapid growth and uncontrolled proliferation of undifferentiated myeloid cells. Metabolic reprogramming is commonly observed in the bone marrow of AML patients, as leukemia cells require increased ATP supply to support disease progression. In this study, we examined the potential role of mesothelin as a metabolic modulator in myeloid cells in AML. Mesothelin is a well-known marker of solid tumors that promotes cancer cell proliferation and survival. We initially analyzed alterations in mesothelin expression in the myeloblast subpopulations, defined as SSC-Alow/CD45dim, obtained from the bone marrow of AML patients using flow cytometry. Our results showed overexpression of mesothelin in 34.8% of AML patients. Subsequently, metabolic changes in leukemia cells were evaluated by comparing the oxygen consumption rates (OCR) of bone marrow samples derived from adult AML patients. Notably, a higher OCR was observed in the mesothelin-positive compared to the mesothelin-low and non-expressing groups. Treatment with recombinant human mesothelin protein enhanced OCR and increased the mRNA expression of glycolytic enzymes and mitochondrial complex II in KG1α AML cells. Notably, siRNA targeting mesothelin in KG1α cells led to the reduction of glycolysis-related gene expression but had no effect on the mitochondrial complex gene. The collective results demonstrate that mesothelin induces metabolic changes in leukemia cells, facilitating the acquisition of a rapid supply of ATP for proliferation in AML. Therefore, the targeting of mesothelin presents a potentially promising approach to mitigating the progression of AML through the inhibition of glycolysis and mitochondrial respiration in myeloid cells.


Assuntos
Leucemia Mieloide Aguda , Mesotelina , Adulto , Humanos , Células Precursoras de Granulócitos/metabolismo , Succinato Desidrogenase/metabolismo , Linhagem Celular Tumoral , Leucemia Mieloide Aguda/genética , Proliferação de Células , Respiração , Glicólise , Trifosfato de Adenosina/metabolismo
3.
PLoS One ; 19(2): e0297758, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38324578

RESUMO

Research on neutrophil biology has been limited by the short life span and limited genetic manipulability of these cells, driving the need for representative and efficient model cell lines. The promyelocytic cell line HL-60 and its subline PLB-985 can be differentiated into neutrophil-like cells (NLCs) and have been used to study neutrophil functions including chemotaxis, phagocytosis, endocytosis, and degranulation. Compared to neutrophils derived from hematopoietic stem cells, NLCs serve as a cost-effective neutrophil model. NLCs derived from both HL-60 and PLB-985 cells have been shown to perform degranulation, an important neutrophil function. However, no study has directly compared the two lines as models for degranulation including their release of different types of mobilizable organelles. Furthermore, Nutridoma, a commercially available supplement, has recently been shown to improve the chemotaxis, phagocytosis, and oxidative burst abilities of NLCs derived from promyelocytic cells, however it is unknown whether this reagent also improves the degranulation ability of NLCs. Here, we show that NLCs derived from both HL-60 and PLB-985 cells are capable of degranulating, with each showing markers for the release of multiple types of secretory organelles, including primary granules. We also show that differentiating HL-60 cells using Nutridoma does not enhance their degranulation activity over NLCs differentiated using Dimethyl Sulfoxide (DMSO) plus Granulocyte-colony stimulating factor (G-CSF). Finally, we show that promyelocytic cells can be genetically engineered and differentiated using these methods, to yield NLCs with a defect in degranulation. Our results indicate that both cell lines serve as effective models for investigating the mechanisms of neutrophil degranulation, which can advance our understanding of the roles of neutrophils in inflammation and immunity.


Assuntos
Neutrófilos , Fagocitose , Humanos , Neutrófilos/metabolismo , Células HL-60 , Diferenciação Celular/fisiologia , Células Precursoras de Granulócitos , Degranulação Celular
4.
BMJ Case Rep ; 17(1)2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38191225

RESUMO

Myeloid sarcoma is a very rare extramedullary malignant tumour, most often associated with acute myeloid leukaemia. We report the case of a man in his early 20s who presented with chronic headache, raised intracranial pressure and progressive vision loss of 2 years duration with no systemic manifestations. He had a history of myeloid sarcoma of the left thigh 15 years ago, treated with external beam radiotherapy and in complete remission for more than 13 years. However, the progressive blindness remained unexplained for 2 years, and he was eventually diagnosed with isolated meningeal relapse without marrow or systemic involvement. Imaging revealed subarachnoid haemorrhage, diffuse leptomeningeal enhancement and involvement of lower dorsal cord and conus, and cerebrospinal fluid cytology showed myeloid blasts. He was managed with intrathecal chemotherapy and craniospinal irradiation, after which he had mild improvement in vision.


Assuntos
Neoplasias Meníngeas , Sarcoma Mieloide , Masculino , Humanos , Sarcoma Mieloide/diagnóstico , Recidiva Local de Neoplasia , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/terapia , Cegueira , Células Precursoras de Granulócitos
5.
Blood Cancer Discov ; 5(3): 180-201, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38442309

RESUMO

In many cancers, mortality is associated with the emergence of relapse with multidrug resistance (MDR). Thus far, the investigation of cancer relapse mechanisms has largely focused on acquired genetic mutations. Using acute myeloid leukemia (AML) patient-derived xenografts (PDX), we systematically elucidated a basis of MDR and identified drug sensitivity in relapsed AML. We derived pharmacologic sensitivity for 22 AML PDX models using dynamic BH3 profiling (DBP), together with genomics and transcriptomics. Using in vivo acquired resistant PDXs, we found that resistance to unrelated, narrowly targeted agents in distinct PDXs was accompanied by broad resistance to drugs with disparate mechanisms. Moreover, baseline mitochondrial apoptotic priming was consistently reduced regardless of the class of drug-inducing selection. By applying DBP, we identified drugs showing effective in vivo activity in resistant models. This study implies evasion of apoptosis drives drug resistance and demonstrates the feasibility of the DBP approach to identify active drugs for patients with relapsed AML. SIGNIFICANCE: Acquired resistance to targeted therapy remains challenging in AML. We found that reduction in mitochondrial priming and common transcriptomic signatures was a conserved mechanism of acquired resistance across different drug classes in vivo. Drugs active in vivo can be identified even in the multidrug resistant state by DBP.


Assuntos
Apoptose , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Leucemia Mieloide Aguda , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/genética , Humanos , Apoptose/efeitos dos fármacos , Animais , Camundongos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Resistência a Múltiplos Medicamentos/genética , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Células Precursoras de Granulócitos/efeitos dos fármacos , Células Precursoras de Granulócitos/patologia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico
9.
Frontiers of Medicine ; (4): 608-620, 2021.
Artigo em Inglês | WPRIM | ID: wpr-888743

RESUMO

t(8;21)(q22;q22) acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy with a high relapse rate in China. Two leukemic myeloblast populations (CD34


Assuntos
Humanos , Expressão Gênica , Células Precursoras de Granulócitos , Imunofenotipagem , Leucemia Mieloide Aguda/genética , Glicoproteínas de Membrana , Prognóstico , Proteínas , Proteínas Proto-Oncogênicas c-kit/genética
10.
Journal of Experimental Hematology ; (6): 1848-1852, 2020.
Artigo em Chinês | WPRIM | ID: wpr-879982

RESUMO

OBJECTIVE@#To analyze the characteristics of volatile organic compounds (VOCs) in expiratory air components of patients with acute promyelocytic leukemia (APL), and assess the feasibility of VOCs for the diagnosis and prognostic evaluation of APL.@*METHODS@#The VOCs exhaled from the patients with APL and healthy volunteers should be analyzed with SPME-GC/MS, and compared between newly-diagnosed group, relapse group, remission group, and healthy group with Wilcoxon/Kruskal-Wallis one-way analysis of variance and Dunn-Bonferroni test.@*RESULTS@#Dimethyl sulfide, toluene, and dodecane obtained of newly-diagnosed APL patients were significantly higher, while ethanol, n-hexanal, and benzaldehyde were significantly lower than those of healthy people (P<0.05). Compared with the newly-diagnosed group, dimethylsulfide, toluene, and dodecane of the remission group significantly decreased, while ethanol, n-hexanal, and benzaldehyde significantly increased (P<0.05), which was just opposite from the relapse group.@*CONCLUSION@#Dimethyl sulfide, toluene, dodecane, ethanol, n-hexanal, and benzaldehyde can be used as biomarkers for the diagnosis and prognosis assessment of APL patients.


Assuntos
Humanos , Expiração , Cromatografia Gasosa-Espectrometria de Massas , Células Precursoras de Granulócitos , Leucemia Promielocítica Aguda/diagnóstico , Compostos Orgânicos Voláteis/análise
11.
Rev. Eugenio Espejo ; 13(2): 62-70, 20191202.
Artigo em Espanhol | LILACS | ID: biblio-1048531

RESUMO

La leucemia es una neoplásica hemática que contiene múltiples subtipos, entre ellos la leucemia promielocítica aguda, caracterizada por la multiplicación clonal del linaje mieloide y eritroide. El presente caso pertenece a un paciente masculino de 20 años, sin antecedentes de importancia y con un cuadro evolutivo de 20 días con sangrado del dedo anular de la mano derecha, y con ausencia de proceso cicatricial. A partir de los exámenes de laboratorio se identifica bicitopénia eritroide y plaquetaria, con evidencia de un 93% de promielocitos. El tratamiento con ATO, ATRA y Antraciclinas logró una leve mejoría. Durante su estadía hospitalaria desarrolló síndrome de diferenciación, lo que ocasionó su fallecimiento.


Leukemia is a hematic neoplastic that contains multiple subtypes, including acute promyelocytic leukemia, characterized by the clonal multiplication of the myeloid and erythroid lineage. The present case belongs to a 20-year-old male patient without health history of importance and with a 20-day evolutionary picture with bleeding from the ring finger of his right hand, and without scarring process. Erythroid and platelet bicytopenia is identified from laboratory tests with evidence of 93% promyelocytes. The treatment including ATO, ATRA and Anthracyclines achieved a slight improvement. He developed differentiation syndrome during hospitalization, which caused his death.


Assuntos
Humanos , Masculino , Adulto , Leucemia Promielocítica Aguda , Células Precursoras de Granulócitos , Hematologia , Medula Óssea , Leucemia , Infiltração-Percolação
12.
Artigo em Coreano | WPRIM | ID: wpr-719664

RESUMO

Neutrophilic leukemoid reaction may occur in many situations, including hemolysis, malignancy, infection, and exposure to certain toxins. It usually shows morphological overlap with chronic myeloid leukemia in which promyelocytes are not majorly associated. Here, we present a case of promyelocytic leukemoid reaction in a patient with sepsis. A 28-year-old man was admitted for renal stone removal. After percutaneous nephrolithotomy, his condition deteriorated with fever (37.8℃), tachycardia (130/min), acute renal failure, pleural effusion, and pulmonary edema. Complete blood count indicated a white blood cell count of 73.39×10⁹/L including 82% promyelocytes, hemoglobin 8.9 g/dL, and platelet count of 85×10⁹/L. A bone marrow aspirate showed that promyelocytes accounted for 73.8% of all nucleated cells. Following bone marrow examination, treatment with all-trans retinoic acid (ATRA) was started immediately. Reverse transcription polymerase chain reaction (RT-PCR) study revealed the absence of PML-RARA (promyelocytic leukemia-retinoic acid receptor alpha) and other RARA (retinoic acid receptor alpha) rearrangements. Once the chromosome analysis of bone marrow cells demonstrated the normal karyotype, ATRA was discontinued.


Assuntos
Adulto , Humanos , Injúria Renal Aguda , Contagem de Células Sanguíneas , Medula Óssea , Células da Medula Óssea , Exame de Medula Óssea , Febre , Células Precursoras de Granulócitos , Hemólise , Cariótipo , Leucemia Mielogênica Crônica BCR-ABL Positiva , Leucemia Promielocítica Aguda , Reação Leucemoide , Contagem de Leucócitos , Nefrostomia Percutânea , Neutrófilos , Contagem de Plaquetas , Derrame Pleural , Reação em Cadeia da Polimerase , Edema Pulmonar , Transcrição Reversa , Sepse , Taquicardia , Tretinoína
13.
Artigo em Inglês | WPRIM | ID: wpr-717639

RESUMO

BACKGROUND: NUP98 has numerous partner genes of which plant homeodomain (PHD) finger protein 23 (PHF23) fusion with NUP98 (NP23) can be detected by RT-PCR in patients with cytogenetically normal acute myelogenous leukemia (AML). In this fusion transcript of NP23 PHD of PHF23 is known to specifically bind H3K4me3 residues and act as a chromatic modifier. Disulfiram (DSF) which inhibits the binding of PHD to H3K4me3 residues selectively killed NP23 myeloblasts in vitro and therefore, we planned to evaluate the efficacy of DSF in vivo. METHODS: Cultured 961C cells (CD45.2), NP23 myeloblast cells were transplanted into B57BL/6 mice (CD45.1). Using limit dilution assay the number of leukemic stem cells (LSCs) could be calculated. A certain amount of 961C cells were transplanted into B57BL/6 mice and DSF was treated after 1 week. The engraftment level was monitored with CD45.2. Kaplan Meier survival curve was used to compare the survival between therapeutic and control group. RESULTS: 961C cells could be transplanted without radiation in recipient mice. Calculated LSC was estimated to be 1 out of 184 cells (95% CI range, 56–609). When treated with DSF of different doses and administration routes in 961C recipient mice no survival advantage of DSF was observed in 961C transplanted immunocompetent mouse, however it was evident that engraftment level was consistent in both groups. CONCLUSION: No survival advantage of DSF in 961C transplanted immunocompetent mouse was observed, however it was evident that 961C cells shared niche with normal hematopoietic stem cells (HSCs). We expect that 961C cells and transplanted recipient mice have the potential to be used as in vivo system for new drugs development as well as for research dealing with niche for normal HSCs and LSCs.


Assuntos
Animais , Humanos , Camundongos , Dissulfiram , Dedos , Células Precursoras de Granulócitos , Células-Tronco Hematopoéticas , Técnicas In Vitro , Leucemia Mieloide Aguda , Plantas , Células-Tronco
14.
Laboratory Medicine Online ; : 167-170, 2018.
Artigo em Coreano | WPRIM | ID: wpr-717394

RESUMO

MPL mutation is an important molecular marker in myeloproliferative neoplasms (MPN). Although MPL W515 is a hot spot for missense mutations in MPN, MPL S505 mutations have been reported in both familial and non-familial MPN. A 72-year-old male visited the hospital, complaining mainly of dizziness and epistaxis. Leukocytosis, anemia, thrombocytopenia, tear drop cells, nucleated RBCs, and myeloblasts were observed in both complete blood cell counts and peripheral blood smears. Bone marrow aspiration failed due to dilution with peripheral blood. BM biopsy indicated hypercellular marrow, megakaryocytic proliferation with atypia, and grade 3 reticulin fibrosis. Conventional cytogenetics results were as follows: 46,XY,del(13)(q12q22)[19]/46,XY[1]. Molecular studies did not detect JAK2 V617F, BCR/ABL translocation, JAK2 exon 12, and CALR exon 9 mutations. The MPL S505N mutation was verified by colony PCR and Sanger sequencing following gene cloning. Based on the above findings, a diagnosis of overt primary myelofibrosis (PMF) was indicated. Mutation studies of buccal and T cells were not conducted. Further, family members were not subjected to mutation studies. Therefore, we were unable to determine whether this mutation was familial or non-familial. Six months after the first visit to the hospital, the patient died due to pneumonia and sepsis. Thrombotic symptoms or major bleeding events did not develop during the survival period following diagnosis of PMF. To the best of our knowledge, this may be the first reported case of PMF with the MPL S505N mutation in Korea.


Assuntos
Idoso , Humanos , Masculino , Anemia , Biópsia , Contagem de Células Sanguíneas , Medula Óssea , Células Clonais , Clonagem de Organismos , Citogenética , Diagnóstico , Tontura , Epistaxe , Éxons , Fibrose , Células Precursoras de Granulócitos , Hemorragia , Coreia (Geográfico) , Leucocitose , Mutação de Sentido Incorreto , Pneumonia , Reação em Cadeia da Polimerase , Mielofibrose Primária , Reticulina , Sepse , Linfócitos T , Lágrimas , Trombocitopenia
15.
Artigo em Inglês | WPRIM | ID: wpr-760476

RESUMO

In patients with acute myeloid leukemia (AML), pleural effusion may be attributed to various factors, including infection, hypoalbuminemia, and renal failure. However, leukemic infiltration of the pleural fluid is rarely reported and poorly understood. Extramedullary diseases have been reported with increasing frequency as the survival rates of patients with AML have increased. However, the reported prognostic effects of leukemic pleural effusion in patients with AML range from none to a worse prognosis. Here, we report a case of acute promyelocytic leukemia (APL) in a patient exhibiting leukemic pleural effusion with fluorescence in situ hybridization (FISH) results indicating the presence of the PML-RARA fusion gene. A 52-year-old man presented with pancytopenia, dyspnea, and fever. He had a medical history of hypertension, end-stage renal disease, and hepatitis B virus-related liver cirrhosis. A peripheral blood smear revealed the presence of multiple abnormally hypergranular promyelocytes. White blood cell differential counts were not performed due to severe pancytopenia. A bone marrow examination, immunophenotyping analysis, and cytogenetic and molecular studies revealed APL. The patient was treated with all-trans retinoic acid immediately after abnormal promyelocytes were observed in the peripheral blood smear, but induction chemotherapy was delayed because of his poor condition. His persistent dyspnea and abdominal discomfort led to a thoracentesis and the observation of abnormal promyelocytes that were positive for PML-RARA fusion gene by FISH. To our knowledge, this is the first report of leukemic pleural infiltration with PML-RARA fusion gene-positivity via FISH.


Assuntos
Humanos , Pessoa de Meia-Idade , Exame de Medula Óssea , Citogenética , Dispneia , Febre , Fluorescência , Células Precursoras de Granulócitos , Hepatite B , Hipertensão , Hipoalbuminemia , Imunofenotipagem , Hibridização In Situ , Quimioterapia de Indução , Falência Renal Crônica , Leucemia Mieloide Aguda , Leucemia Promielocítica Aguda , Infiltração Leucêmica , Leucócitos , Cirrose Hepática , Pancitopenia , Derrame Pleural , Prognóstico , Insuficiência Renal , Taxa de Sobrevida , Toracentese , Tretinoína
16.
Artigo em Inglês | WPRIM | ID: wpr-301049

RESUMO

<p><b>OBJECTIVE</b>To study the efficacy and safety of Shuanghuang Shengbai Granule (, SSG), a traditional Chinese herbal medicine, on myelosuppression of cancer patients caused by chemotherapy.</p><p><b>METHODS</b>A total of 330 patients were randomly assigned to the treatment group (220 cases, analysed 209 cases) and the control group (110 cases, analysed 102 cases) with a 2:1 ratio by envelope method. The patients in the treatment group at the first day of chemotherapy started to take SSG for 14 days, while the patients in the control group took Leucogon Tablets. The changes of the blood routine, clinical symptoms and immune function in both groups were observed for safety and efficacy evaluation.</p><p><b>RESULTS</b>At the 7th day of chemotherapy, the white blood cells (WBCs) level in the treatment group was significantly higher than that in the control group (P<0.05). After treatment, the WBCs rate in the normal range accounted for 50.2% in the treatment group, the myelosuppression of WBCs and neutrophil were mainly grade I, while 8.1% and 5.7% of patients emerged grade III and grade IV myelosuppression, respectively. The incidence of myelosuppression of the treatment group was significantly lower than that of the control group (P<0.05). The total effective rate of Chinese medicine syndrome in the treatment group was significantly higher than that in the control group (84.2% vs. 72.5%, P<0.05). The immune cell levels in both groups were maintained in the normal range. Compared with that before treatment, the levels of CD3and CD4cells were significantly increased in the treatment group after treatment (P<0.05). The discrepancy of CD3and CD4cell activity before and after treatment in both groups were significantly different (P<0.05). No obvious adverse event occurred in both groups.</p><p><b>CONCLUSION</b>SSG had a protection effect on bone marrow suppression, and alleviated the clinical symptoms together with clinical safety.</p>


Assuntos
Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antineoplásicos Fitogênicos , Usos Terapêuticos , Protocolos de Quimioterapia Combinada Antineoplásica , Usos Terapêuticos , Medicamentos de Ervas Chinesas , Usos Terapêuticos , Células Precursoras de Granulócitos , Tolerância Imunológica , Medicina Tradicional Chinesa , Neoplasias , Tratamento Farmacológico , Pancitopenia , Resultado do Tratamento
17.
An. pediatr. (2003. Ed. impr.) ; 84(4): 195-202, abr. 2016. tab, graf
Artigo em Espanhol | IBECS (Espanha) | ID: ibc-151005

RESUMO

INTRODUCCIÓN: La leucemia mieloblástica aguda (LMA) constituye la segunda hemopatía maligna en la población pediátrica y una de las principales causas de mortalidad por cáncer infantil. La supervivencia se sitúa alrededor del 60% sin haber mejorado en las últimas décadas, por lo que son necesarios nuevos enfoques terapéuticos. El efecto antileucémico ejercido por los linfocitos y las células natural killer (NK) del sistema inmunológico está bien establecido en el trasplante de células madre hematopoyéticas pero también como estrategia de inmunoterapia adoptiva tras la quimioterapia de consolidación. PACIENTES Y MÉTODOS: De manera retrospectiva, se analizan las características clínicas de los pacientes diagnosticados de LMA en nuestro centro durante el período 1996-2014. Además en 10 leucemias agudas, 5 linfoides y 5 mieloides, se analizaron la intensidad media de fluorescencia de HLA-I, MICA-B, ULBP1-4, ligandos para los receptores de las células NK. RESULTADOS: Un total de 67 pacientes formaron parte de este análisis. La supervivencia libre de eventos con una mediana de seguimiento de 25 meses fue del 62% (IC del 95%, 55-67). Las LMA con menor supervivencia fueron las secundarias, las no M3 y las carentes de marcadores citogenéticos favorables. La probabilidad de recaída fue del 38% (IC del 95%, 31-45). La expresión de HLA-I y ULBP-4 fue significativamente menor en los blastos mieloides que en los linfoides. CONCLUSIONES: Nuestros resultados clínicos son similares a los descritos en la literatura. No se ha modificado significativamente la supervivencia en las últimas décadas y la probabilidad de recaída sigue siendo elevada. Los blastos mieloides podrían ser más susceptibles a las células NK al expresar menos HLA-I, por lo que estrategias de terapia celular podrían ser eficaces tal y como reportan otros grupos


INTRODUCTION: Acute myeloid leukaemia (AML) is the second haematological malignancy in the paediatric population, and one of the leading causes of childhood cancer mortality. Survival is currently around 60%, with no improvement in last decades, suggesting that new therapeutic approaches are needed. The anti-leukaemia effect mediated by the lymphocytes and natural killer (NK) cells of the immune system has been established in haematopoietic stem cell transplantation, and also as adoptive immunotherapy after consolidation chemotherapy schemes. PATIENTS AND METHODS: A retrospective study was conducted on the clinical characteristics of patients diagnosed and treated for AML in our centre during 1996-2014. The mean fluorescence intensities of HLA-I, MICA/B and ULBP1-4, ligands for NK cell receptors, were also analysed in ten new diagnosed leukaemia cases, five myeloid and five lymphoid. RESULTS: A total of 67 patients were used in this analysis. With a median follow up of 25 months, the event-free survival was 62% (95% CI: 55-67). Secondary AML, non-M3 phenotype, and the absence of favourable cytogenetic markers had a lower survival. The probability of relapse was 38% (95% CI: 31-45). The expression of HLA-I and ULBP-4 was significantly lower in myeloid than in lymphoid blast cells. CONCLUSIONS: Our clinical results are similar to those described in the literature. Survival did not significantly change in recent decades, and the likelihood of relapse remains high. Myeloid blasts might be more susceptible to the cytotoxicity of NK cells through their lower expression of HLA-I. NK therapy strategies in minimal disease situation could be effective, as reported by other groups


Assuntos
Humanos , Masculino , Feminino , Leucemia/epidemiologia , Leucemia/genética , Leucemia/mortalidade , Células Precursoras de Granulócitos/imunologia , Células Matadoras Naturais/citologia , Células Matadoras Naturais/imunologia , Histocompatibilidade , Sobrevivência , Quimioterapia Combinada/instrumentação , Quimioterapia Combinada/métodos , Quimioterapia Combinada , Imunoterapia/instrumentação , Imunoterapia/métodos , Imunoterapia , Estudos Retrospectivos
18.
Artigo em Inglês | WPRIM | ID: wpr-108391

RESUMO

Myeloid sarcoma (MS) is an extramedullary involvement of immature myeloid proliferation. An isolated MS is defined as a myeloblastic tumor when it arises without any concomitant circulating disease. A diagnosis of MS is established using pathologic features including infiltration of myeloblasts and strong myeloperoxidase expression with negative cytokeratin immunohistochemical staining. We report a rare case of colonic MS without any peripheral blood abnormality. If the affected patient were left untreated, the MS could evolve into acute myeloid leukemia (AML) within one year. Several studies recommend the same regimens of chemotherapy as used for circulating AML to treat isolated MS. We focused on the diagnosis of MS in this study. The correct diagnosis of MS is important for adequate treatment. In conclusion, MS should be considered in the differential diagnosis of intestinal tumor.


Assuntos
Humanos , Colo , Neoplasias do Colo , Diagnóstico , Diagnóstico Diferencial , Tratamento Farmacológico , Células Precursoras de Granulócitos , Intestinos , Queratinas , Leucemia Mieloide Aguda , Peroxidase , Sarcoma Mieloide
19.
Artigo em Chinês | WPRIM | ID: wpr-360092

RESUMO

<p><b>OBJECTIVE</b>To investigate the immunophenotype of leukemia promyelocytes (LP) in bone marrow of patients with acute promyelocytic leukemia (APL) and to explore their characteristics and significance.</p><p><b>METHODS</b>The immunophenotypes of leukemia cells in 43 patients with APL were analyzed by means of 4 color immunophenotypes; the cell population in which CD45 strength localized at 10(2) and the SSC strength locatized at 10(2) was defined as R3, the cell population in which CD45 strength localized at 10(3) and the SSC strength localized at 10(2) was defined as R5, moreover the ratio of positive cells >80% was defined as strong positive expression, the ratio of positive cells between 20%-80% was difined as weak positive expression, the ratio of positive cells <20% was difined as negative by gating method of CD45/SSC.</p><p><b>RESULTS</b>There was a abnormal cell population (R3) in 79.07% cases; the immunophenotypes of R3 was cheracteried by high SSC, weaker expression of CD45, the rate of CD38, CD9 and CD13 all was 100%, moreover their bright expression (>80%) was 86.05%, 90.70% and 86.05%, respectively; the positive expression rate of CD33, CD117 and CD64 was 97.67%, 95.35% and 83.80% respectively, moreover thier bright expression was 84.04%, 69.77% and 30.23% respectively; the CD15 was weakly expressed in 39.53% cases, the CD34 and HLA-DR were weakly expression in 16.28% and 6.98% cases respectively. All the cases did not express CD116. There were 2 cell populations (R3 and R5) in 20.93% cases, the immunophenotypic features of R3 were cosistant with above mentioning, while the immunophenotypes of R5 were lower than those of R3 SSC; the fluorescence intensity of CD45 was higher, but lower than that in normal lymphycytes, the positive rate of CD9, CD13, MPO was 100%, moreover thier fluorescence intensity was high; they did not expressed CD123, CD25, CD22, CD4, CD64 and CD14. Thereby it can be concluded that the typical immunophenotypes is characterized by CD13(+) CD9(+) CD38(+) CD33(+) CD117(+) CD64(+) CD11b(-) CD34(-) HLA-DR(-) in APL. There was a special immunophenotype in the APL with basophilic granules. Conclusoin: APL has a characteristic immunophenotypic profile, whose typical immunophenotype is characterized by CD13(+) CD9(+) CD38(+) CD33(+) CD117(+) CD64(+) CD11b(-) CD34(-) HLA-DR(-). The special immunophenotype exists in the APL with basophilic granules. Flow cytometric immunophenotyping may be a useful for rapid recognition of APL and has significant for prognosis.</p>


Assuntos
Humanos , Antígenos CD , Metabolismo , Contagem de Células , Citometria de Fluxo , Células Precursoras de Granulócitos , Classificação , Antígenos HLA-DR , Metabolismo , Imunofenotipagem , Leucemia Promielocítica Aguda , Classificação , Alergia e Imunologia , Antígenos Comuns de Leucócito , Metabolismo , Prognóstico
20.
Artigo em Coreano | WPRIM | ID: wpr-160929

RESUMO

PURPOSE: To report a case of an 82-year-old male with acute myeloid leukemia presenting with bilateral isolated conjunctival and eyelid masses. CASE SUMMARY: An 82-year-old male presented with a bilateral conjunctival mass and right eyelid mass occurring 10 days prior. He was diagnosed with prostate cancer 8 years ago and complete recovery was achieved using selective mass chemotherapy. He experienced a stroke 4 years ago and was treated using a carotid artery stent insertion and medication. In the initial laboratory test, hemoglobin was 13.7 g/dL and leukocyte count 5,530/mm3(neutrophil 74.4%, lymphocyte 10%, monocyte 11.8%). Light reflex, movement of extraocular muscle and fundus examination were all normal. Biopsy was performed 1 week after the first visit. Seven days after biopsy, he complained of sudden dyspnea and febrile sense and was admitted to the intensive care unit via the emergency room (ER). The laboratory tests performed in the ER showed hemoglobin was 9.6 g/dL and leukocyte count was 78,020/mm3(neutrophil 0%, lymphocyte 7%, monocyte 5%, promyelocyte 1%, metamyelocyte 4%, myelocyte 6%, blast 67%). The biopsy revealed diffuse proliferation of atypical plasmacytoid cells, consistent with leukemic infiltration. Under the diagnosis of acute myeloid leukemia, chemotherapy was administered. However, the patient died due to aggravated pneumonia. CONCLUSIONS: Even if non-specific findings appear on the peripheral blood tests, eyelid and conjunctival masses should be considered as possible tumors in acute myeloid leukemia.


Assuntos
Idoso de 80 Anos ou mais , Humanos , Masculino , Biópsia , Artérias Carótidas , Túnica Conjuntiva , Diagnóstico , Tratamento Farmacológico , Dispneia , Serviço Hospitalar de Emergência , Pálpebras , Células Precursoras de Granulócitos , Testes Hematológicos , Unidades de Terapia Intensiva , Leucemia Mieloide Aguda , Infiltração Leucêmica , Contagem de Leucócitos , Linfócitos , Monócitos , Pneumonia , Neoplasias da Próstata , Reflexo , Sarcoma Mieloide , Stents , Acidente Vascular Cerebral
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