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2.
Article in Chinese | WPRIM | ID: wpr-888377

ABSTRACT

OBJECTIVE@#To explore the phenotypic and genetic characteristics of acute megakaryoblastic leukemia (AMKL) in young children accompany by WT1, MLL-PTD and EVI1, in order to improve the diagnosis level of AMKL.@*METHODS@#EDTA-K@*RESULTS@#White blood cell count was 12.3× 10@*CONCLUSION@#Acute megakaryocytic leukemia has unique and complex phenotypic and genetics characteristics.


Subject(s)
Bone Marrow , Child , Child, Preschool , Chromosome Aberrations , Humans , Karyotyping , Leukemia, Megakaryoblastic, Acute/genetics , MDS1 and EVI1 Complex Locus Protein , Megakaryocytes , Oncogene Proteins, Fusion , WT1 Proteins
3.
Journal of Experimental Hematology ; (6): 1577-1581, 2021.
Article in Chinese | WPRIM | ID: wpr-922298

ABSTRACT

OBJECTIVE@#To investigate the effect of enhanced autophagy in megakaryocyte to proplatelet formation in children with immune thrombocytopenia(ITP).@*METHODS@#Giemsa staining and immunofluorescence staining were used to observe megakaryocyte morphology and proplatelet formation, Western blot was used to determine the expression of cytoskeleton protein and autophagy related protein. Autophagr regulation drugs Rap or 3-MA was used to regulate autophagy of megakaryocytes.@*RESULTS@#Some vacuole-like structures was found in ITP megakaryocytes of the children, the expression of LC3II/I (ITP 1.32±0.18; Ctrl 0.49±0.16,P<0.05) and Atg5-Atg12 (ITP 0.69±0.17; Ctrl 0.12±0.08,P<0.05) was significantly higher in ITP children as compared with those in control group. The immu- nofluorescence staining showed that the cytoskeleton arrangement in megakaryocytes of ITP children was abnormal, and the phosphorylation of myosin light chain was also increased(ITP 0.74±0.09, Ctrl 0.05±0.02,P<0.05). In vitro, inducer or inhibitor of autophagy could regulate the production of proplatelet and the expression of cell cycle related protein, including CyclinD1(Veh 1.08±0.12; Rap 0.46±0.04; Rap+3-MA 0.70±0.03), CyclinD2(Veh 0.47±0.04; Rap 0.27±0.04; Rap+3-MA 0.41±0.03), P21(Veh 0.15±0.01; Rap 0.04±0.01; Rap+3-MA 0.05±0.01).@*CONCLUSION@#Enhanced autophagy is the key factor of poor proplatelet formation in megakaryocytes of ITP children.


Subject(s)
Autophagy , Blood Platelets , Humans , Megakaryocytes , Purpura, Thrombocytopenic, Idiopathic , Thrombocytopenia
5.
Journal of Experimental Hematology ; (6): 2039-2045, 2020.
Article in Chinese | WPRIM | ID: wpr-880012

ABSTRACT

OBJECTIVE@#To compare the effect of Sheng-Xue-Xiao-Ban Capsule (SXXBC) and indirubin to the peripheral platelets of the Idiopathic thrombocytopenic purpura (ITP) model mouse.@*METHODS@#The ITP mouse model was established by the method of passive immunization. SXXBC and indirubin were used for intervention treatment. Then the hemorrhagic phenomena of ITP mice were observed and the numbers of peripheral platelets, hemoglobin and white blood cells, bone marrow megakaryocytes and their classification and coagulation function were detected and compared.@*RESULTS@#The improvement rate of hemorrhage in SXXBC group was 40% for small dose, 60% for medium dose and 80% for high dose, while the improvement rate of hemorrhage in indirubin group was 30% for small dose, 50% for medium dose and 60% for high dose. There was no statistically significant difference in the improvement rate of hemorrhage between the two groups (P>0.05). Compared with the model control group, PLT and Hb increased in different doses of SXXBC and indirubin group 4th-8th day after drug intervention (P<0.05, 0.01). However, there was no significant difference between the different doses of SXXBC group and indirubin group (P>0.05). Compared with the model control group, the WBC in each group was significantly lower (P<0.05, 0.01) on the 4th-8th day after drug intervention; However, there was no statistical significance between the two groups of SXXBC and indirubin (P>0.05). Compared with the model control group, the total number of megakaryocytes in each treatment group were decreased (P<0.05, P<0.01), in which the number of primary megakaryocytes in the large and medium dose groups of SXXBC and indirubin were decreased (P<0.05, 0.01), and the number of juvenile megakaryocytes in the large dose group of SXXBC and indirubin were also decreased (P<0.05). The number of granular megakaryocytes were decreased in each intervention groups (P<0.05, 0.01), and the number of thromocytogenic megakaryocyte was increased in the high and medium dose groups of SXXBC and indirubin (P<0.01). The time of prothrombin was shortened in the high and medium dose groups of SXXBC and indirubin (P<0.05), and the fibrinogen (FIB) content in the high and medium dose groups of SXXBC was close to that of the normal control group.@*CONCLUSION@#Both of the SXXBC and the indirubin standard all show good hemostatic effects. Indirubin shows a positive effect on increasing the peripheral platelet and hemoglobin in ITP model mice, regulating the immune response, reducing the total number of bone marrow megakaryocytes, increasing the thromocytogenic megakaryocyte, and increasing coagulation function.


Subject(s)
Animals , Blood Platelets , Capsules , Indoles , Megakaryocytes , Mice , Purpura, Thrombocytopenic, Idiopathic/drug therapy
6.
Article in Chinese | WPRIM | ID: wpr-828907

ABSTRACT

OBJECTIVE@#To explore whether thrombopoietin (TPO) can rescue megakaryopoiesis by protecting bone marrowderived endothelial progenitor cells (BM-EPCs) in patients receiving chemotherapy for hematological malignancies.@*METHODS@#Bone marrow samples were collected from 23 patients with hematological malignancies 30 days after chemotherapy and from 10 healthy volunteers. BM-EPCs isolated from the samples were identified by staining for CD34, CD309 and CD133, and their proliferation in response to treatment with TPO was assessed using CCK8 assay. DiL-Ac-LDL uptake and FITC-UEA-I binding assay were performed to evaluate the amount of BM-EPCs from the subjects. Tube-formation and migration experiments were used for functional assessment of the BM-EPCs. The BM-EPCs with or without TPO treatment were co-cultured with human megakaryocytes, and the proliferation of the megakaryocytes was detected with flow cytometry.@*RESULTS@#Flow cytometry indicated that the TPO-treated cells had high expressions of CD34, CD133, and CD309. CCK8 assay demonstrated that TPO treatment enhanced the proliferation of the BM-EPCs, and the optimal concentration of TPO was 100 μg/L. Double immunofluorescence assay indicated that the number of BM-EPC was significantly higher in TPO-treated group than in the control group. The TPO-treated BM-EPCs exhibited stronger tube-formation and migration abilities ( < 0.05) and more significantly enhanced the proliferation of co-cultured human megakaryocytes than the control cells ( < 0.05).@*CONCLUSIONS@#TPO can directly stimulate megakaryopoiesis and reduce hemorrhage via protecting the function of BM-EPCs in patients following chemotherapy for hematological malignancies.


Subject(s)
Bone Marrow , Bone Marrow Cells , Cells, Cultured , Hematologic Neoplasms , Humans , Megakaryocytes , Thrombopoietin
7.
Journal of Experimental Hematology ; (6): 1044-1048, 2020.
Article in Chinese | WPRIM | ID: wpr-827164

ABSTRACT

Abstract  Hematopoietic stem cells are able to self-renewal and differentiate to all blood lineages. With the development of new technologies, recent studies have proposed the revised versions of hematopoiesis. In the classical model of hematopoietic differentiation, HSCs were located at the apex of hematopoietic hierarchy. During differentiation process, HSCs progressively lose self-renewal potential to be commited to progenitors with restricted differentiation potential. For instance, HSCs first give rise to multipotent progenitor cells, then produce bipotent and unipotent progenitors, and finally differentiate to mature blood cells. For the differentiation of megakaryocytes, common myeloid progenitors derived from HSCs give rise to megakaryocyte-erythrocyte progenitors and then develop to megakaryocytes. However, recent results show that megakaryocytes can be directly generated from HSCs without multipotent or bipotent phases. Alternatively, platelet-biased HSCs produce megakaryocyte progenitors. In this article, recent advances in the hematopoiesis and megakaryocyte differentiation pathway are reviewed.


Subject(s)
Cell Differentiation , Cell Lineage , Hematopoiesis , Hematopoietic Stem Cells , Megakaryocytes , Multipotent Stem Cells
8.
Journal of Experimental Hematology ; (6): 1332-1337, 2020.
Article in Chinese | WPRIM | ID: wpr-827116

ABSTRACT

OBJECTIVE@#To investigate the influencing factors on prognosis of adult patients with chronic primary immune thrombocytopeuia (ITP) after rituximab treatment and predictive value of platelet (Plt) count.@*METHODS@#Clinical data of 52 adult patients with chronic primary ITP treated with rituximab from January 2012 to December 2016 were retrospectively analyzed, including 32 patients for failed in treatment as group A and 20 patients for succeeded in treatment as group B. The independent risk factors influencing the clinical efficacy of rituximab were analyzed. The influence of CD41 megakaryocyte count in bone marrow diagnosed for first time on the response rate of patients with 1-year followed-up were observed, and the Plt count were calculated to predict the clinical efficacy index and the best cut-off point.@*RESULTS@#The CD41 megakaryocyte count in bone marrow for first time treatment in group B were significantly higher than that in group A (P<0.05). Multivariate Logistic regression analysis showed that the number of CD41 megakaryocytes in bone marrow<150 at first diagnosis was the independent risk factor influencing the clinical efficacy of rituximab (OR=5.40,95%CI:1.82-15.66,P=0.00). The response rate of 1-year followed-up in patients with CD41 megakaryocyte count ≥150 at first diagnosis was significantly higher than that of CD41 megakaryocyte count <150 (P<0.05). The Plt count level in group B was significantly lower than that in group A at the 3rd, 14th, 21th, 30th, 60th, 90th, 180th, 270th and 360th days after first treatment with rituximab (P<0.05). ROC curve analysis showed that the best cut-off point for Plt count was 50×10/L and AUC was 0.68 at the 14th day after first treatment with rituximab (95%CI: 0.57-0.78, P=0.00). The predictive sensitivity and specificity of clinical efficacy in adult patients with chronic primary ITP treated with rituximab were separately 48.73% and 87.58%, and the AUC in 30th and 60th day after rituximab treatment were separately 0.74 (95%CI: 0.64-0.87, P=0.00), 0.93 (95%CI:0.82-0.98,P=0.00).@*CONCLUSION@#Adult patients with chronic primary ITP may possess long-term remission after rituximab treatment, but the prognosis is poor for patients with bone marrow megakaryocyte count <150. The Plt counts in 14th, 30th and 60th days after rituximab treatment can effectively predict the long-term clinical efficacy and guide the formulation of treatment plans.


Subject(s)
Adult , Humans , Megakaryocytes , Platelet Count , Prognosis , Purpura, Thrombocytopenic, Idiopathic , Retrospective Studies , Rituximab
9.
Journal of Experimental Hematology ; (6): 1357-1362, 2020.
Article in Chinese | WPRIM | ID: wpr-827112

ABSTRACT

OBJECTIVE@#To explore the method for inducing the differentiation of bone marrow cells into megakaryocytes in vitro so as to use for evaluating the activity of traditional Chinese medicines.@*METHODS@#The bone marrow cells were separated from femurs and tibias of mice. The experiments were divided into 4 groups: control (no adding cytokines), TPO (adding 50 ng/ml TPO), TPO+SCF (50 ng/ml+50 ng/ml) and TPO+SCF+IL-6+IL-9 (50 ng/ml+50 ng/ml+20 ng/ml+20 ng/ml). The bone marrow cells in 4 groups were cultured in vitro for 6 d. Then the cell growth status was observed by the inverted microscopy, and the cell count was detected by using the automatic cell counter. The ratio and absolute count of megakaryocytes were detected by flow cytometry.@*RESULTS@#Compared with control, three induction methods could stimulate the differentiation of bone marrow cells into megakaryocytes in vitro. TPO could slightly enhance the differentiation of bone marrow cells into megakaryocytes. Both the combination of TPO and SCF, and the combination of TPO, SCF, IL-6 and IL-9 could intensively stimulate proliferation of bone morrow cells and promote the differentiation of bone marrow cells into megakaryocytes. The addition of IL-6 and IL-9 could decrease the proliferation of non-megakaryocytes, but promote the differentiation of bone marrow cells into megakaryocytes.@*CONCLUSION@#The optimized differentiation of bone marrow cells into megakaryocytes has been completed by co-induction regimen of TPO, SCF, IL-6 and IL-9, which can be used to screen and evaluate traditional Chinese medicines promoting formation of platelets.


Subject(s)
Animals , Bone Marrow Cells , Cell Count , Cell Differentiation , Cell Division , Cells, Cultured , Interleukin-3 , Megakaryocytes , Mice , Stem Cell Factor , Thrombopoietin
10.
An. Facultad Med. (Univ. Repúb. Urug., En línea) ; 6(2): 25-34, dic. 2019. ilus, graf
Article in Spanish | LILACS, BNUY, UY-BNMED | ID: biblio-1291263

ABSTRACT

El estudio de la megacariopoyesis humana se ha visto obstaculizado por la relativa escasez de megacariocitos en la médula ósea (0,05-0,2 % de las células medulares), lo que ha llevado a la optimización de protocolos de expansión in vitro a partir de precursores de diversos orígenes (cordón umbilical, médula ósea y sangre periférica con o sin movilización previa). Los cultivos celulares a partir de precursores han permitido la producción y el estudio tanto de megacariocitos así como de proplaquetas y plaquetas Sin embargo, la producción in vitro óptima de megacariocitos que culminen todos los estadios de diferenciación es un reto aún no resuelto. En este trabajo reportamos los hallazgos concernientes a la determinación de las condiciones y concentraciones de trombopoyetina para lograr una óptima relación entre la cantidad de trombopoyetina empleada y el porcentaje y grado de diferenciación megacariocítica en muestras obtenidas de cinco donantes alogénicos aceptados para trasplante de médula ósea.


The study of human megakaryocytopoiesis has been hampered by the relative scarcity of megakaryocytes in bone marrow (0.05-0.2 % of medullary cells), which has led to the optimization of protocols of in vitro expansion of precursors from diverse sources (umbilical cord, bone marrow and peripheral blood with or without previous mobilization). Cell cultures from different precursors have allowed the production and study of megakaryocytes as well as proplatelets and platelets. However, the in vitro production of megakaryocytes that culminate all stages of differentiation is a challenge that has not yet been resolved. In this work we report the findings related to the determination of thrombopoietin treatment conditions and concentrations to achieve an optimal relationship between the amount of thrombopoietin and the percentage and degree of megakaryocytic differentiation in five allogeneic donors that were accepted for bone marrow transplantation.


O estudo da megacariopoiese humana tem sido dificultado pela relativa escassez de megacariócitos na medula óssea (0,05-0,2 % das células medulares), o que levou à otimização dos protocolos de expansão in vitro a partir de precursores de diversas origens (cordão umbilical, medula óssea e sangue periférico com ou sem mobilização prévia). Culturas de células a partir de precursores permitiram a produção e o estudo tanto de megacariócitos e de proplaquetas e plaquetas. No entanto, a produção ótima in vitro de megacariócitos que culminam em todas as fases de diferenciação é um desafio ainda não resolvido. Neste trabalho, relatamos as descobertas relativas à determinação das condições e concentrações de trombopoietina para obter uma relação ótima entre a quantidade de trombopoietina usada e a taxa e o grau de diferenciação megacariocítica em amostras obtidas de cinco doadores alogênicos aceitos para transplante de medula óssea.


Subject(s)
Humans , Thrombopoietin/analysis , Megakaryocytes/cytology , Antigens, CD34/analysis , Cells, Cultured/cytology , Leukapheresis , Protocols , Platelet Membrane Glycoprotein IIb/analysis , Integrin beta3/analysis , Culture Techniques/methods
11.
Braz. dent. j ; 30(1): 12-21, Jan.-Feb. 2019. tab, graf
Article in English | LILACS | ID: biblio-989433

ABSTRACT

Abstract This study aimed to assess the effects of low molecular weight heparin (LMWH) on alveolar bone loss (ABL), blood count, and counting of megakaryocytes and adipocytes in male Wistar rats. Forty male 60-day Wistar rats were randomly divided into four groups: Control (C), Periodontal Disease (PD), Heparin (Hp) and Heparin + Periodontal Disease (Hp+PD). LMWH was applied for 60 days at doses of 1 ml/kg/day. Blood samples were collected at baseline, 30 and 60. On day-49, PD and Hp+PD groups were subjected to ligature-induced periodontitis around second upper right molar. The left side was assessed as spontaneous alveolar bone loss. Mean ABL in the side with ligature showed significantly different between C (0.35±0.07 mm) and Hp+DP (0.49±0.09 mm) groups (p<0.001), between PD (0.55±0.11 mm) and Hp (0.32±0.06 mm) groups (p<0.001) and between Hp and Hp+DP groups (p<0.001). No significant differences were found among groups for ABL in the side without ligature. Animal weight, food intake, and water consumption showed no statistically significant difference among groups. Megakaryocytes and adipocytes were counted using optical microscopy and no statistically significant differences were found. Within-groups, there were an increase and a decrease, respectively, in the counting of lymphocytes (p=0.005 for C and p=0.009 for Hp+PD groups only) and leukocytes (p=0.003 for C, p=0.001 for PD, p=0.002 for Hp, and p<0.001 for Hp+PD groups). There was no decrease in the number of platelets in the three collection periods. LMWH was not able to affect ABL, but it may change the blood counting, especially increasing lymphocytes.


Resumo O presente estudo objetivou verificar o efeito da heparina de baixo peso molecular (HBPM) sob a perda óssea alveolar (POA), contagem de células sanguíneas, megacariócitos e adipócitos em ratos Wistar machos. Quarenta ratos Wistar de 60 dias foram randomicamente divididos em quatro grupo: Controle (C), Doença Periodontal (DP), Heparina (Hp) e Heparina + Doença Periodontal (Hp+DP). HBPM foi aplicada durante 60 dias em doses de 1 mL/kg/dia. Coletas sanguíneas foram realizadas nos dias 0, 30 e 60. No dia 49, os grupos DP e Hp+DP receberam indução de doença periodontal por ligadura ao redor do segundo molar superior direito. No lado esquerdo, verificou-se perda óssea alveolar espontânea. A média de POA no lado com ligadura mostrou-se estatisticamente diferente entre os grupos C (0,35±0,07 mm) e Hp+PD (0,49±0,09 mm) (p<0,001), entre os grupos DP (0,55±0,11 mm) e Hp (0,32±0,06 mm) (p<0,001) e entre os grupos Hp e Hp+DP (p<0,001). Nenhuma diferente significativa foi observada entre os grupos no lado sem ligadura. Peso dos animais, consumo de ração e ingestão de água não mostraram diferenças significativas entre os grupos. Megacariócitos e adipócitos foram contados por microscopia óptica e nenhuma diferença significativa foi encontrada. Dentro dos grupos, houve um aumento e uma diminuição, respectivamente, na contagem de linfócitos (p=0,005 no grupo C e p=0,009 no grupo Hp+DP somente) e leucócitos (p=0,003 no grupo C, p=0.001 no grupo DP e p=0,002 no grupo Hp e Hp+DP). Não houve diminuição no número de plaquetas nos três períodos de coleta. HBPM não foi capaz de modificar a POA, porém modificou a contagem de células sanguíneas, especialmente aumentando o número de linfócitos.


Subject(s)
Animals , Male , Rats , Alveolar Bone Loss/prevention & control , Heparin, Low-Molecular-Weight/pharmacology , Megakaryocytes/cytology , Rats, Wistar , Adipocytes/cytology , Heparin, Low-Molecular-Weight/administration & dosage , Dose-Response Relationship, Drug
12.
Journal of Experimental Hematology ; (6): 1949-1954, 2019.
Article in Chinese | WPRIM | ID: wpr-781513

ABSTRACT

OBJECTIVE@#To investigate the changes of mean platelet volume (MPV), platelet distribution width (PDW) and platelet associated antibodies (PAIg) in children with acute immune thrombocytopenic purpura (aITP), and to explore the diagnostic value of MPV, PDW, PAIg and their combination for megakaryocyte dysmaturity in aITP children.@*METHODS@#Plt count, MPV and PDW of 36 aITP children were measured by using Sysmex XN automatic blood cell analyzer, and 33 children with acquired thrombocytopenic purpura (ATP) without megakaryocyte dysmaturity. The expression of PAIg was detected by flow cytometry, and the number and classification of megakaryocytes in the bone marrow were performed by marrow cytology. The diagnostic significances of MPV, PDW, PAIg and their combination as well as the sensitivity and specificity for megakaryocytes dysmaturity in aITP were assessed through calculating the area under ROC curve (AUC), after determining the influence of each parameters on the megakaryocyte dysmaturity by Logistic regression.@*RESULTS@#MPV, PDW and PAIg of aITP children were significantly higher than those of the ATP children (P<0.05), while the Plt count and number of thromocytogenic megakaryocytes per area (1.5 cm×3 cm) were less than those of the controls (P<0.05). Count of RBC and WBC, percentages of neutrophil granulocytes and lymphocydes in aITP were similar to those in the controls(P>0.05). The results of Logistic regression showed that Plt count, MPV, PDW and PAIg were the factors influencing megakaryocyte dysmaturity in aITP children, and the regression model has a high statistical significance (χ=65.491,P=0.001) and r square (R=0.713). The AUC of the combined detection of Plt count, MPV, PDW and PAIg was 0.863, which was much higher than that of Plt count, MPV, PDW, PAIg individually or in pairs. The sensitivity and specificity of the combined detection were 79.167% and 89.697%, which were higher than those of Plt count, MPV, PDW, PAIg individually or in pairs.@*CONCLUSION@#The diagnostic significance of MPV and PDW for megakaryocyte dysmaturity in aITP are insufficient, but the diagnostic efficacy can be improved by combined examination with PAIg.


Subject(s)
Antibodies , Blood Platelets , Child , Humans , Mean Platelet Volume , Megakaryocytes , Platelet Count , Purpura, Thrombocytopenic, Idiopathic , Diagnosis
13.
Article in English | WPRIM | ID: wpr-762438

ABSTRACT

POEMS syndrome is a rare paraneoplastic syndrome, which includes polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes due to plasma cell (PC) neoplasm. Diagnosis of this disease is challenging because of its rarity and complex clinical manifestations. We attempted to identify the key clinical features and characteristic bone marrow (BM) findings of POEMS syndrome, by reviewing the medical records and BM analyses of 24 Korean patients. Frequent clinical manifestations included polyneuropathy (100%), monoclonal gammopathy (100%), organomegaly (92%), extravascular volume overload (79%), and endocrinopathy (63%). The BM analyses revealed mild PC hyperplasia (median PCs: 5.5%) and frequent megakaryocytic hyperplasia (88%), megakaryocyte clusters (88%), and hyperlobation (100%). Flow cytometry of BM aspirates using CD138/CD38/CD45/CD19/CD56 showed normal (67%, 4/6) or neoplastic PC immunophenotypes (33%, 2/6). A diagnosis of POEMS syndrome must be considered when a patient suspected of having PC dyscrasia shows the above clinical presentation and BM findings.


Subject(s)
Bone Marrow , Diagnosis , Flow Cytometry , Humans , Hyperplasia , Medical Records , Megakaryocytes , Paraneoplastic Syndromes , Paraproteinemias , Plasma Cells , POEMS Syndrome , Polyneuropathies , Skin
14.
INSPILIP ; 2(2): 1-12, jul.-dic. 2018.
Article in Spanish | LILACS | ID: biblio-981634

ABSTRACT

La Histoplasmosis es una infección micóticaoportunista, frecuente en pacientes con infección por virus de inmunodeficiencia humana (VIH) y síndrome de inmunodeficiencia adquirida (SIDA). La mayoría de las veces suele ser asintomática, pudiendo asociarse a hemorragia, destrucción acelerada de las plaquetas y descenso de la hemopoyesis debido a infección de los megacariocitos. Este reporte trata de un paciente con diagnóstico reciente de infección por VIH, por cuadro de 1 mes de evolución caracterizado por fiebre, malestar general y pérdida de peso mayor a 10% de la masa ponderal. Durante su hospitalización se realizaron estudios de imágenes y laboratorio para tamizaje de infecciones oportunistas. La evolución clínica inicialmente estuvo marcada por deterioro progresivo del estado general, con alteraciones persistentes de las plaquetas y de la serie eritroide, por lo que fue evaluado por el servicio de Hematología, que realizó la punción biopsia por aspiración de médula ósea (BAMO) para descartar malignidad hematológica y compromiso medular por agentes oportunistas.


Histoplasmosisis an opportunistic fungal infection, frequent in patients with infection by human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS). Most of the time it is usually asymptomatic, and it can be associated with hemorrhage, the accelerated destruction of platelets and the decrease in hemopoiesis due to an infection of megakaryocytes. This report is based on a recent diagnosis of HIV infection, in a picture of evolution of fever, malaise and weight loss greater than 10% of body weight.During his hospitalization, imaging and laboratory studies are carried out to screen for opportunistic infections. Clinical evolution remained marked by progressive general state, with persistent alterations of platelets and erythroid series, so it was evaluated by the hematology service, which performed the bone marrow aspiration biopsy (BAMO) to rule out Hematological malignancy and spinal commitment by opportunistic agents.


Subject(s)
Male , Megakaryocytes , AIDS-Related Opportunistic Infections , Mycoses , Histoplasma , Infections
15.
Journal of Experimental Hematology ; (6): 1876-1880, 2018.
Article in Chinese | WPRIM | ID: wpr-774368

ABSTRACT

The main physiological function of megakaryocytes is the production of platelets, whose development, maturation and platelet production are a complex regulatory process, and are involved in many factors. In recent years it was found that the lung is also the main site of megakaryocyte-producing platelets in addition to bone marrow. Based on the findings of recent years, this review summarizes the process of megakaryocyte development, maturation and platelet production, with emphasis on the analyzing the regulatory effects of apoptotic factors, miRNA, thrombopoietin and its receptors, interleukins, transcription factors and their corresponding signal pathways on platelet production. To understand the regulatory mechanism of platelet production can help to understand the pathological mechanism of platelet-related diseases and provide new ideas for the diagnosis and treatment of platelet-related diseases.


Subject(s)
Blood Platelets , Bone Marrow Cells , Megakaryocytes , Thrombopoiesis , Thrombopoietin
16.
Laboratory Animal Research ; : 166-175, 2018.
Article in English | WPRIM | ID: wpr-719077

ABSTRACT

Recombination activating gene-2 (RAG-2) plays a crucial role in the development of lymphocytes by mediating recombination of T cell receptors and immunoglobulins, and loss of RAG-2 causes severe combined immunodeficiency (SCID) in humans. RAG-2 knockout mice created using homologous recombination in ES cells have served as a valuable immunodeficient platform, but concerns have persisted on the specificity of RAG-2-related phenotypes in these animals due to the limitations associated with the genome engineering method used. To precisely investigate the function of RAG-2, we recently established a new RAG-2 knockout FVB mouse line (RAG-2(−/−)) manifesting lymphopenia by employing a CRISPR/Cas9 system at Center for Mouse Models of Human Disease. In this study, we further characterized their phenotypes focusing on histopathological analysis of lymphoid organs. RAG-2(−/−) mice showed no abnormality in development compared to their WT littermates for 26 weeks. At necropsy, gross examination revealed significantly smaller spleens and thymuses in RAG-2(−/−) mice, while histopathological investigation revealed hypoplastic white pulps with intact red pulps in the spleen, severe atrophy of the thymic cortex and disappearance of follicles in lymph nodes. However, no perceivable change was observed in the bone marrow. Moreover, our analyses showed a specific reduction of lymphocytes with a complete loss of mature T cells and B cells in the lymphoid organs, while natural killer cells and splenic megakaryocytes were increased in RAG-2(−/−) mice. These findings indicate that our RAG-2(−/−) mice show systemic lymphopenia with the relevant histopathological changes in the lymphoid organs, suggesting them as an improved Rag-2-related immunodeficient model.


Subject(s)
Animals , Atrophy , B-Lymphocytes , Bone Marrow , Genome , Homologous Recombination , Humans , Immunoglobulins , Killer Cells, Natural , Lymph Nodes , Lymphocytes , Lymphopenia , Megakaryocytes , Methods , Mice , Mice, Knockout , Negotiating , Phenotype , Receptors, Antigen, T-Cell , Recombination, Genetic , Sensitivity and Specificity , Severe Combined Immunodeficiency , Spleen , T-Lymphocytes , Thymus Gland
18.
Korean Journal of Medicine ; : 546-551, 2017.
Article in Korean | WPRIM | ID: wpr-103595

ABSTRACT

A 37-year-old female presented to our hospital with a history of bleeding episodes (excessive bleeding after tooth extraction, gum bleeding, easy bruising, and excessive menstruation) and severe thrombocytopenia (2,000/µL). She had no family history of bleeding tendency or thrombocytopenia. No peripheral lymphadenopathy or splenomegaly was noted. The patient's white blood cell count was normal; hemoglobin was 9.7 g/dL. A peripheral blood smear showed markedly decreased platelets, with occasional giant or large platelets. Bone marrow examination found increased megakaryocytes. The patient also complained of hearing difficulty; a hearing test indicated sensory-neural hearing impairment. Her thrombocytopenia was refractory to treatment with glucocorticosteroids, intravenous gamma-globulin, and danazol. In the 13 years following her initial presentation, the patient required anti-hypertensive treatment, a hearing-aid for progressive hearing loss, and started maintenance kidney dialysis. Her clinical history of refractory thrombocytopenia, progressive hearing impairment, and renal failure suggested myosin heavy chain 9 gene-related congenital syndrome (Epstein syndrome), which was confirmed by the presence of a heterozygous deletion mutation, c.221_223del, (p.Lys74del) in peripheral leukocyte deoxyribonucleic acid.


Subject(s)
Adult , Bone Marrow Examination , Danazol , Dialysis , DNA , Female , gamma-Globulins , Gingiva , Hearing , Hearing Loss , Hearing Loss, Sensorineural , Hearing Tests , Hemorrhage , Humans , Kidney , Leukocyte Count , Leukocytes , Lymphatic Diseases , Megakaryocytes , Myosin Heavy Chains , Renal Insufficiency , Renal Insufficiency, Chronic , Sequence Deletion , Splenomegaly , Thrombocytopenia , Tooth Extraction
19.
Acta bioquím. clín. latinoam ; 50(2): 233-245, jun. 2016. ilus, tab
Article in Spanish | LILACS | ID: biblio-837602

ABSTRACT

Tal vez por haber sido consideradas como simples restos citoplasmáticos de los megacariocitos encargadas únicamente de la reparación de heridas, las plaquetas han tenido un lugar secundario en cuanto a su estudio e interés en comparación con los otros componentes celulares de la sangre. Sin embargo, en los últimos 20 años se ha avanzado mucho en el conocimiento de estas fascinantes células que de a poco han recobrado un lugar destacado dentro de la hematología. A lo largo de este trabajo se han revisado los aportes más destacados y novedosos acerca del proceso de biogénesis plaquetaria, su regulación por el microambiente medular y factores humorales, recorriendo desde la generación de megacariocitos hasta la liberación de plaquetas libres.


Perhaps for being considered mere megakaryocyte cytoplasmic debris responsible for wound repair alone, platelets have had a secondary role when compared to other cellular blood components. However, in the last 20 years we have learned much more about these fascinating cells, which have slowly regained a prominent place in hematology. This review discusses the most outstanding and novel contributions on platelet biogenesis, its regulation by the bone marrow microenvironment and humoral factors, analyzing from megakaryocyte generation to platelet release.


Talvez por ter sido considerados simples restos citoplasmáticos dos megacariócitos, encarregadas apenas da reparação de feridas, as plaquetas têm tido um lugar secundário quanto a seu estudo e interesse em comparação com os outros componentes celulares do sangue. Entretanto, nos últimos 20 anos foi possível aprender muito a respeito destas fascinantes células que aos poucos foram recobrando um lugar de destaque dentro da hematologia. Ao longo deste trabalho foram revistas as contribuições mais destacadas e novas acerca do processo de biogênese plaquetária, sua regulação pelo microambiente medular e fatores humorais, percorrendo desde a geração de megacariócitos até a liberação de plaquetas livres.


Subject(s)
Female , Megakaryocytes , Cells , Origin of Life , Cytoplasm , Hematology
20.
Korean Journal of Medicine ; : 288-292, 2016.
Article in Korean | WPRIM | ID: wpr-167772

ABSTRACT

Although there have been substantial advances in confirming diagnoses and defining the molecular characteristics of polycythemia vera (PV) and essential thrombocythemia (ET), treatments for these conditions remain elementary. The main goal is still mainly focused on reducing the risk of thrombosis. The prevention of hemorrhage, leukemia transformation, and progression to myelofibrosis has yet to be established. To reduce the risk of thrombosis, risk-adapted treatment is recommended. Phlebotomy is the most important and effective treatment modality for patients with erythrocytosis, while cytoreduction using hydroxyurea, busulfan, or interferon-α is an ancillary treatment for patients at high risk for thrombosis. Anagrelide is used to decrease platelet counts in patients with thrombocytosis by inhibiting the maturation of platelets from megakaryocytes. Recent trials have shown that ruxolitinib, a Janus kinase (JAK) inhibitor, has clinical benefits in patients with polycythemia vera who show an inadequate response, or unacceptable side effects, to therapeutic doses of hydroxyurea. Theoretically, JAK inhibitors may also delay the progression of leukemia transformation and myelofibrosis but there is still no evidence of this. The cost of JAK inhibitors for the treatment of patients with PV/ET is a difficult hurdle for its use as a first-line treatment.


Subject(s)
Busulfan , Diagnosis , Hemorrhage , Humans , Hydroxyurea , Janus Kinases , Leukemia , Megakaryocytes , Phlebotomy , Phosphotransferases , Platelet Count , Polycythemia Vera , Polycythemia , Primary Myelofibrosis , Thrombocythemia, Essential , Thrombocytosis , Thrombosis
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