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1.
Article in Chinese | WPRIM | ID: wpr-878706

ABSTRACT

The self-renewal and differentiation of hematopoietic stem cells(HSCs)are highly regulated by epigenetic modification,in which histone acetylation can activate or silence gene transcription.Histone deacetylase inhibitors(HDACIs)can inhibit the activity of histone deacetylase in HSCs to increase histone acetylation.A variety of HDACIs,such as trichostatin A and valproic acid,are used to expand HSCs in vitro,especially cord blood HSCs,combined with cytokines in serum-free culture to obtain more long-term repopulating cells.HDACIs promote the transcription of pluripotent genes related to stem cell self-renewal and inhibit the expression of genes related to differentiation,so as to promote the expansion and inhibit differentiation of HSCs.The expansion of cord blood HSCs by small molecular HDACIs in vitro is expected to improve the quantity of cord blood HSCs.The further research will focus on high-throughput screening for the most powerful HDACIs and the highly selective HDACIs,exploring the combination of epigenetic modifiers of different pathways.


Subject(s)
Epigenesis, Genetic , Fetal Blood , Hematopoietic Stem Cells , Histone Deacetylase Inhibitors/pharmacology , Valproic Acid/pharmacology
2.
Article in Chinese | WPRIM | ID: wpr-880170

ABSTRACT

OBJECTIVE@#To analyze the dynamic molecular expression characteristics of single cell RNA binding proteins (RBPs) in the development of mouse embryonic hematopoitic stem cells (HSCs), and obtain the functional research target RNA splicing factor--Mbnl1, to clarify the function of Mbnl1 involved in regulating mouse embryonic HSC development.@*METHODS@#Bioinformatics was used to analyze the single-cell transcriptome data of mouse embryos during HSC development, and the single-cell RBP dynamic molecular expression maps in HSC development was obtained. Mbnl1 was obtained by combining differential analysis and literature research screening. The Mbnl1-knockout mouse model was constructed by the CRISPER/Cas9 technology. Aorta-gonad-mesonephros (AGM) and yolk sac (YS) tissue in two genotype embryos of Mbnl1@*RESULTS@#The in vitro CFU-C experiment of hematopoietic cells preliminarily indicated that there was no significant difference in the number of cell colonies in AGM region and YS transformed by the two genotypes of Mbnl1@*CONCLUSION@#Through functional experiments in vivo and in vitro, it has been confirmed that knockout of the RNA splicing factor--Mbnl1 does not affect the development of HSPC in AGM region of mouse embryo.


Subject(s)
Animals , DNA-Binding Proteins , Gonads , Hematopoiesis , Hematopoietic Stem Cells , Mesonephros , Mice , RNA-Binding Proteins/genetics , Yolk Sac
3.
Article in Chinese | WPRIM | ID: wpr-880072

ABSTRACT

The normal hematopoiesis of the body are depends on the proliferation and differentiation of hematopoietic stem/progenitor cell (HSPC), as well as the mesenchymal stem/stromal cell (MSC) that support the growth and development of hematopoietic microenvironment of bone marrow (BM). At present, the commonly used MSC for promoting hematopoiesis are mainly derived from BM, however, the acquisition of MSC from BM is limited by the number, sampling, isolation and purification. Compared with BM, adipose tissue has many advantages, including widely distributed, abundant in source, simple and easy to obtain, and contains more pluripotent stem cell, such as adipose tissue-derived stem cell (ADSC), in which Perivascular cell/pericyte (PC) are considered as the precursor cell of MSC, also is the main components of vascular microenvironment, and plays an important role in the proliferation and differentiation of HSPC. PC is especially abundant in adipose tissue, and with the advantages of easy acquisition, small damage, fast cell proliferation and low immunogenicity. Therefore, the sustaining hematopoiess of human adipose derived-perivascular stem cell (AD-PC) to HSPC requires further research and exploration. In this review, the possible supporting effects and PC subgroup of ADSC as stromal cell on HSPC are summarized briefly.


Subject(s)
Adipose Tissue , Bone Marrow Cells , Cell Differentiation , Cell Proliferation , Cells, Cultured , Hematopoietic Stem Cell Transplantation , Hematopoietic Stem Cells , Humans , Mesenchymal Stem Cells
4.
Article in Chinese | WPRIM | ID: wpr-879807

ABSTRACT

OBJECTIVE@#To study the association of different maternal and infant factors with the number of total nucleated cells and CD34@*METHODS@#A prospective study was performed for the umbilical cord blood samples of 130 neonates who were born in Dalian Women and Children's Medical Center from June 2019 to January 2020, with a male/female ratio of 1:1. Related perinatal information was collected, including maternal age and blood type, presence or absence of gestational diabetes or gestational hypertension, pregnancy method, mode of delivery, singleton pregnancy/twin pregnancy, body weight and sex of neonates, Apgar score after birth, and the conditions of placenta, amniotic fluid, and umbilical cord.@*RESULTS@#The neonates were grouped according to maternal blood type, gestational diabetes, gestational hypertension, pregnancy method, mode of delivery, singleton pregnancy/ twin pregnancy, sex of neonates, Apgar score after birth, placental morphology, meconium staining of amniotic fluid, and umbilical cord around the neck. The comparison between groups showed no significant differences in the numbers of total nucleated cells and CD34@*CONCLUSIONS@#The number of CD34


Subject(s)
Antigens, CD34 , Female , Fetal Blood , Hematopoietic Stem Cell Transplantation , Hematopoietic Stem Cells , Humans , Infant , Infant, Newborn , Male , Pregnancy , Prospective Studies , Umbilical Cord
5.
Adv Rheumatol ; 61: 9, 2021. tab, graf
Article in English | LILACS | ID: biblio-1152744

ABSTRACT

Abstract Background: In the past 20 years, hematopoietic stem cell transplantation (HSCT) has been investigated as treatment for systemic sclerosis (SSc). The goal of HSCT is to eradicate the autoreactive immune system, which is replaced by a new immune repertoire with long-lasting regulation and tolerance to autoantigens. Here, we describe the clinical outcomes of severe and refractory SSc patients that underwent HSCT at a single Brazilian center. Patients and methods: This is a longitudinal and retrospective study, including 70 adult SSc patients, with an established diagnosis of SSc, and who underwent autologous HSCT from 2009 to 2016. The procedure included harvesting and cryopreservation of autologous hematopoietic progenitor cells, followed by administration of an immunoablative regimen and subsequent infusion of the previously collected cells. Patients were evaluated immediately before transplantation, at 6 months and then yearly until at least 5-years of post-transplantation follow-up. At each evaluation time point, patients underwent clinical examination, including modified Rodnan's skin score (mRSS) assessment, echocardiography, high-resolution computed tomography of the lungs and pulmonary function. Results: Median (range) age was 35.9 (19-59), with 57 (81.4%) female and median (range) non-Raynaud's disease duration of 2 (1-7) years. Before transplantation, 96% of the patients had diffuse skin involvement, 84.2%, interstitial lung disease and 67%, positive anti-topoisomerase I antibodies. Skin involvement significantly improved, with a decline in mRSS at all post-transplantation time points until at least 5-years of follow-up. When patients with pre-HSCT interstitial lung disease were analyzed, there was an improvement in pulmonary function (forced vital capacity and diffusing capacity of lung for carbon monoxide) over the 5-year follow-up. Overall survival was 81% and progression-free survival was 70.5% at 8-years after HSCT. Three patients died due to transplant-related toxicity, 9 patients died over follow-up due to disease reactivation and one patient died due to thrombotic thrombocytopenic purpura. Conclusions: Autologous hematopoietic progenitor cell transplantation improves skin and interstitial lung involvement. These results are in line with the international experience and support HSCT as a viable therapeutic alternative for patients with severe and progressive systemic sclerosis.(AU)


Subject(s)
Humans , Adult , Scleroderma, Systemic/surgery , Hematopoietic Stem Cells , Cryopreservation/instrumentation , Hematopoietic Stem Cell Transplantation/instrumentation , Disease Progression , Retrospective Studies , Longitudinal Studies
6.
Lima; Perú. Ministerio de Salud; 20201000. 17 p. ilus.
Monography in Spanish | LILACS, MINSAPERU | ID: biblio-1121864

ABSTRACT

Contiene los lineamientos técnicos para la captación de potenciales donantes no emparentados de células progenitoras hematopoyéticas en el contexto de una epidemia o pandemia producida por microorganismos que se transmiten por vía área.


Subject(s)
Hematopoietic Stem Cells , Donor Selection , Epidemics
7.
Estud. Interdiscip. Psicol ; 11(2): 167-197, maio-ago.2020. Tab
Article in Portuguese | LILACS | ID: biblio-1342145

ABSTRACT

Este estudo teve por objetivo conhecer as percepções e vivências do acompanhante familiar diante do adoecer e do transplante de células-tronco hematopoéticas (TCTH) à luz da teoria do luto antecipatório. Trata-se de um estudo exploratório com abordagem qualitativa, do qual participaram 11 familiares. As entrevistas individuais foram organizadas pela análise temática e interpretados em três níveis contextuais, envolvendo mudanças intrapsíquicas, interacionais com o paciente e no âmbito familiar/social. Constatou-se que o familiar experimenta sentimentos e reações emocionais consistentes com o processo de enlutamento. As mudanças na interação com o paciente acontecem desde os primeiros sintomas e intensificam-se com a necessidade de fornecer cuidado integral na enfermaria durante o transplante. Transformações na dinâmica familiar acontecem em resposta às perdas de papéis sociais, ocupacionais e seus impactos financeiros. Ademais, o sofrimento experimentado pelo cuidador durante esse processo não é legitimado, tanto pela família quanto pela equipe de saúde, já que do acompanhante se exige que seja uma fonte de apoio inabalável (AU).


This study aimed to know the perceptions and experiences of family companions facing illness and transplantation of hematopoietic stem cells (HSCT) in light of the theory of anticipatory grief. This is an exploratory study with a qualitative approach, in which 11 relatives participated. The individual interviews were organized by thematic analysis and interpreted at three contextual levels, involving intra-psychic, interactional with the patient and family / social changes. It was found that the family member experiences feelings and emotional reactions consistent with the bereavement process. Changes in patient interaction occur from the earliest symptoms and intensify with the need to provide comprehensive nursing care during transplantation. Transformations in family dynamics occur in response to the loss of social, occupational roles and their financial impacts. Moreover, the suffering experienced by the caregiver during this process is not validated, either by the family or by the healthcare providers, as the companion is required to be an unshakable source of support (AU).


Este estudio tuvo como objetivo conocer las percepciones y experiencias del compañero familiar cuando se enfrenta a una enfermedad y el trasplante de células madre hematopoyéticas (TCMH) a la luz de la teoría del duelo anticipatorio. Este es un estudio exploratorio con un enfoque cualitativo, en el que participaron 11 familiares. Las entrevistas individuales fueron organizadas por análisis temático e interpretadas en tres niveles contextuales, involucrando intrapsíquica, interacción con el paciente y cambios familiares / sociales. Se descubrió que el miembro de la familia experimenta sentimientos y reacciones emocionales consistentes con el proceso de duelo. Los cambios en la interacción con el paciente ocurren desde los primeros síntomas y se intensifican con la necesidad de proporcionar atención integral de enfermería durante el trasplante. Las transformaciones en la dinámica familiar ocurren en respuesta a la pérdida de roles sociales, ocupacionales y sus impactos financieros. Además, el sufrimiento experimentado por el cuidador durante este proceso no está legitimado, ni por la familia ni por el equipo de salud, ya que el acompañante debe ser una fuente de apoyo inquebrantable (AU).


Subject(s)
Humans , Male , Female , Hematopoietic Stem Cells , Bereavement , Family , Caregivers , Stem Cell Transplantation , Emotions , Grief
8.
Infectio ; 24(2): 126-128, abr.-jun. 2020. graf
Article in Spanish | LILACS, COLNAL | ID: biblio-1114852

ABSTRACT

Resumen La linfohistiocitosis hemofagocítica (LHH) por Histoplasma capsulatum, presentación rara de la histoplasmosis diseminada, es causada por la fagocitosis de las células hematopoyéticas por macrófagos tisulares. Presentamos el caso de un paciente masculino de 44 años con trasplante renal que asiste por fiebre sin otra sintomatología. Inicialmente se obtiene una gota gruesa positiva para P. vivax, iniciando manejo antimalárico. A los 2 días de tratamiento, el paciente presenta disfunción multiórganica, se rectifica diagnóstico en centro de referencia reportando en extendido de sangre periférica la presencia de levaduras de H. capsulatum en polimorfonucleares, resultado confirmado con prueba de inmunodifusión. Se ajusta manejo, pero el paciente fallece. El diagnóstico de infecciones por gérmenes inusuales con presentaciones inespecíficas es un reto en pacientes con inmunosupresión.


Abstract Hemophagocytic Lymphohistiocytosis (HLH) induced by Histoplasma capsulatum is a rare entity who is characterized by phagocytosis of hematopoietic cells by tissue macrophages. A 44-year-old male patient with kidney transplantation was admitted to our ambulatory service with fever. Initially, we performed a thick drop test who was positive for P. vivax, so antimalarial therapy was initiated. Patient then progressed to multiple organ dysfunction after 2 days of treatment. Thus, a reference center went back over the blood smear which revealed the presence of yeast cells H. capsulatum within polymorphonuclear cells. This result was confirmed by an immunodifussion assay. Despite of antifungal treatment, patient passed away. The diagnosis for unusual microorganism with unspecific clinical presentation could be a challenge in immunosupressive patients.


Subject(s)
Humans , Male , Adult , Lymphohistiocytosis, Hemophagocytic , Phagocytosis , Hematopoietic Stem Cells , Kidney Transplantation , Histoplasma
9.
Autops. Case Rep ; 10(2): e2020147, Apr.-June 2020. graf
Article in English | LILACS | ID: biblio-1131811

ABSTRACT

In adults, B-lymphocytes comprise approximately 10% of circulating lymphocytes. The majority of peripheral B cells are B2 cells ("Mature" B-cells), which function as part of the humoral adaptive immune system. B1 cells ("Innate-like" B cells) are another sub-class of B lymphocytes, considered as innate immune cells with a characteristic phenotype (CD20+, CD27+, CD43+, CD70-, CD11b+, sIgM++, sIgD+) which can be divided into two subtypes; B1a (CD5+): spontaneously produce broadly reactive natural IgM, and B1b (CD5-): can generate T-cell independent, long-lasting IgM. There is very limited data available, indicating a correlation between allogeneic bone marrow transplantation and an increase in B1a cells. Here we present a case of a 17-year-old female with homozygous sickle cell disease (HbSS disease) who underwent hematopoietic stem cell transplant (HSCT). Approximately seven months post-transplant, she was found to have 16% immature mononuclear cells on complete blood count (CBC)-differential report. A follow-up peripheral blood flow cytometry showed that these cells were polyclonal CD5+/CD20+ B-cells, and comprised 66% of lymphocytes. Further workup and follow up failed to reveal any lymphoproliferative disorders. It is important not to misdiagnose these cells as an atypical CD5+ lymphoproliferative disorder. The presence of B1a cells has not been widely reported in non-neoplastic post-stem cell transplanted patients. This case also adds to and expands our knowledge regarding the presence of increased circulating B1a cells after stem cell transplant in a patient with no history of hematological malignancy.


Subject(s)
Humans , Female , Adolescent , Stem Cell Transplantation/adverse effects , Blood Cell Count , Hematopoietic Stem Cells , B-Lymphocytes/cytology , B-Lymphocyte Subsets/pathology , Flow Cytometry , Anemia, Sickle Cell , Lymphoproliferative Disorders/diagnosis
11.
Journal of Experimental Hematology ; (6): 1025-1031, 2020.
Article in Chinese | WPRIM | ID: wpr-827167

ABSTRACT

OBJECTIVE@#To investigate the prevalence of respiratory viral infections in patients with primary immunodeficiency disease (PID) during hematopoietic stem cell transplantation.@*METHODS@#108 specimens of nasopharyngeal aspirate were collected from 22 PID patients before and after hematopoietic stem cell transplantation from July 2016 to July 2018 in the Department of Hematology. The TR-PCR was used to detect for respiratory viruses including respiratory syncytial virus(RSV),human metapneumoviros(hMPV),coronavirus(CoV) and parainfluenza 1-3 (PIV1-3). And the clinical characteristics and co-infection were analyzed.@*RESULTS@#Among the total 108 specimens, viral pathogens were identified in 41 (37.96%) specimens. Among which the pathogens of highest detection rate was RSV (25.9%). Different types of PID showed different virus infection rates, among which the highest infection rate was severe combined immunodeficiency disease (SCID) patients, with the virus detection rate was 57.9%. The incidence of co-infection with two or more than two viruses was 19.5%.@*CONCLUSION@#Patients with PID who undergo hematopoietic stem cell transplantation are more susceptible to respiratory viruses. RSV is an important respiratory tract virus pathogen after hematopoietic stem cell transplantation.


Subject(s)
Hematopoietic Stem Cell Transplantation , Hematopoietic Stem Cells , Humans , Metapneumovirus , Primary Immunodeficiency Diseases , Therapeutics , Respiratory Syncytial Virus, Human , Respiratory Tract Infections
12.
Journal of Experimental Hematology ; (6): 1038-1043, 2020.
Article in Chinese | WPRIM | ID: wpr-827165

ABSTRACT

Abstract  Hematopoietic stem cells (HSCs), as a kind of adult stem cell, is first used in clinical practice. It has been widely used in hematopoietic stem cell transplantation and has broad application prospects in the field of gene therapy. However, the shortage of HSC is still the main bottleneck restricting the clinical application of HSC transplantation, especially cord blood HSC transplantation. With the continuous improvement of the concept of HSC and the in-depth study of the molecular mechanism regulating HSC self-renewal and differentiation, it have been explored that a variety of strategies for ex vivo expansion of HSC, such as adding small molecule compounds in vitro culture system, simulating bone marrow microenvironment, regulating HSC metabolism and biomaterial-based amplification methods. In this review, recent advances in research of ex vivo expansion strategy of HSC are summarized and discussed.


Subject(s)
Bone Marrow , Cell Differentiation , Hematopoietic Stem Cell Transplantation , Hematopoietic Stem Cells
13.
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
14.
Journal of Experimental Hematology ; (6): 1283-1291, 2020.
Article in Chinese | WPRIM | ID: wpr-827125

ABSTRACT

OBJECTIVE@#To analyze the effect of clinical features, routine laboratory examination and related gene mutation on the OS of patients with myelodysplastic syndrome (MDS) after hematopoietic stem cell transplantation (HSCT).@*METHODS@#121 patients diagnosed as MDS and underwent hematopoietic stem cell transplantation in the First Affiliated Hospital of Soochow University from October 2013 to August 2018 were selected. Basic information of the patients was collected, and blood cells, bone marrow blasts at initial diagnosis, chromosomal karyotypes and gene mutations of the patients were detected.The effect of different factors on overall survival (OS) was analyzed by statistical method.@*RESULTS@#Kaplan-Meier univariate analysis shows that OS was significanly different among different age groups. The 3-year OS rate of patients aged 0-29 years was (83.3±7.7) %, the 3-year OS rate in patients aged 30-49 years was (58.1±7.7 %), and the 3-year OS rate of patients aged 50-69 years was (31.0±22.6) %, which was statistically different (P<0.05) between different groups. There were also significant differences in OS among patients with different transplantation types. 3-year OS rate: HLA-matched sibling HSCT>unrelated HLA-matched HSCT>haploidentical HSCT>micro HSCT. The OS rate of patients with bone marrow blasts≥10% seems lower than blasts<10%, but there was no statistical difference.The 3-year OS rate of patients with chromosomal karyotype complex abnormality was (47.7±11.5) %, and that of patients without complex abnormality was (80±4.2) % which was statistical difference (P<0.05). Patients with DNMT3A, NRAS, TP53 and GATA2 mutations had shorter OS time compared with patients without mutation of these genes, which shows statistically significant (P<0.05). COX multivariate analysis showed that age, chromosome karyotype, DNMT3A, TET2, GATA2 and NRAS were the independent factors influencing OS of patients after HSCT, with statistically significant difference.@*CONCLUSION@#age of patients, donor selection of HSCT, chromosome karyotype, DNMT3A, NRAS, TP53, GATA2 and TET2 gene mutations are all independent factors affecting the OS of patients after HSCT. Therefore, the assessment of the OS of MDS patients with transplantation requires comprehensive consideration.


Subject(s)
Adolescent , Adult , Aged , Child , Child, Preschool , Hematopoietic Stem Cell Transplantation , Hematopoietic Stem Cells , Humans , Infant , Infant, Newborn , Middle Aged , Myelodysplastic Syndromes , Prognosis , Retrospective Studies , Siblings , Survival Analysis , Young Adult
15.
Acta Physiologica Sinica ; (6): 167-174, 2020.
Article in Chinese | WPRIM | ID: wpr-827071

ABSTRACT

Humans with chronic psychological stress are prone to develop multiple disorders of body function including impairment of immune system. Chronic psychological stress has been reported to have negative effects on body immune system. However, the underlying mechanisms have not been clearly demonstrated. All immune cells are derived from hematopoietic stem cells (HSC) in the bone marrow, including myeloid cells which comprise the innate immunity as a pivotal component. In this study, to explore the effects of chronic psychological stress on HSC and myeloid cells, different repeated restraint sessions were applied, including long-term mild restraint in which mice were individually subjected to a 2 h restraint session twice daily (morning and afternoon/between 9:00 and 17:00) for 4 weeks, and short-term vigorous restraint in which mice were individually subjected to a 16 h restraint session (from 17:00 to 9:00 next day) for 5 days. At the end of restraint, mice were sacrificed and the total cell numbers in the bone marrow and peripheral blood were measured by cell counting. The proportions and absolute numbers of HSC (LinCD117Sca1CD150CD48) and myeloid cells (CD11bLy6C) were detected by fluorescence activated cell sorting (FACS) analysis. Proliferation of HSC was measured by BrdU incorporation assay. The results indicated that the absolute number of HSC was increased upon long-term mild restraint, but was decreased upon short-term vigorous restraint with impaired proliferation. Both long-term mild restraint and short-term vigorous restraint led to the accumulation of CD11bLy6C cells in the bone marrow as well as in the peripheral blood, as indicated by the absolute cell numbers. Taken together, long-term chronic stress led to increased ratio and absolute number of HSC in mice, while short-term stress had opposite effects, which suggests that stress-induced accumulation of CD11bLy6C myeloid cells might not result from increased number of HSC.


Subject(s)
Animals , Antigens, Ly , Metabolism , Bone Marrow Cells , Cell Biology , CD11b Antigen , Metabolism , Cell Proliferation , Hematopoietic Stem Cells , Cell Biology , Mice , Mice, Inbred C57BL , Restraint, Physical , Stress, Psychological
16.
Blood Research ; : 17-26, 2020.
Article in English | WPRIM | ID: wpr-820807

ABSTRACT

BACKGROUND: DNMT3A mutations occur in approximately 20% of AML cases and are associated with changes in DNA methylation. CDKN2B plays an important role in the regulation of hematopoietic progenitor cells and DNMT3A mutation is associated with CDKN2B promoter methylation. We analyzed the characteristics of DNMT3A mutations including their clinical significance in AML and their influence on promoter methylation and CDKN2B expression.METHODS: A total of 142 adults, recently diagnosed with de novo AML, were enrolled in the study. Mutations in DNMT3A, CEBPA, and NPM1 were analyzed by bidirectional Sanger sequencing. We evaluated CDKN2B promoter methylation and expression using pyrosequencing and RT-qPCR.RESULTS: We identified DNMT3A mutations in 19.7% (N=28) of enrolled patients with AML, which increased to 29.5% when analysis was restricted to cytogenetically normal-AML. Mutations were located on exons from 8–23, and the majority, including R882, were found to be present on exon 23. We also identified a novel frameshift mutation, c.1590delC, in AML with biallelic mutation of CEBPA. There was no significant difference in CDKN2B promoter methylation according to the presence or type of DNMT3A mutations. CDKN2B expression inversely correlated with CDKN2B promoter methylation and was significantly higher in AML with R882H mutation in DNMT3A. We demonstrated that DNMT3A mutation was associated with poor AML outcomes, especially in cytogenetically normal-AML. The DNMT3A mutation remained as the independent unfavorable prognostic factor after multivariate analysis.CONCLUSION: We characterized DNMT3A mutations in AML and revealed the association between the DNMT3A mutation and CDKN2B expression and clinical outcome.


Subject(s)
Adult , DNA Methylation , Exons , Frameshift Mutation , Hematopoietic Stem Cells , Humans , Leukemia, Myeloid, Acute , Methylation , Multivariate Analysis
17.
Odontol. vital ; (30): 31-38, ene.-jun. 2019. tab, graf
Article in Spanish | LILACS, SaludCR | ID: biblio-1091410

ABSTRACT

Resumen Objetivo: Describir la incidencia y el puntaje de la mucositis oral (MO) y las morbilidades relacionadas en individuos sometidos a trasplante de células madre hematopoyéticas (TCMH) a lo largo del período de inmunosupresión. Métodos: Los sujetos con enfermedades onco / hematológicas, mayores de 14 años, sometidos a TCMH alogénico fueron evaluados diariamente por la presencia y clasificación de OM, nivel de dolor, disfagia, disgeusia y xerostomía. El examen comenzó dos días antes de la infusión de células madre hematopoyéticas y finalizó veinte días después. La OM se clasificó de acuerdo con la escala de la OMS y se utilizó la escala analógica visual (EVA) para medir el nivel de dolor. Resultados: Se reclutaron 23 individuos, el 83% con enfermedades malignas y el 91% con OM. La mediana del grado máximo de OM fue 3 y el nivel máximo de dolor fue 9. Hubo una mediana de 11 días de uso de medicación opioide. Los sujetos que tuvieron el mayor número de días con dolor en la boca alcanzaron el grado máximo de OM y el mayor número de días y el uso de opioides. Conclusión: Hubo una alta incidencia y puntuaciones más altas de OM, pérdida de masa corporal y dolor en esta muestra.


Abstract Aim: To describe the oral mucositis (OM)` incidence and score, and related morbidities in individuals submitted to Hematopoietic Stem Cell Transplantation (HSCT) throughout the immunosuppression period of time. Methods: Subjects with onco / hematological diseases, older than 14 years, submitted to allogeneic HSCT were daily evaluated by the presence and classification of OM, pain level, dysphagia, dysgeusia and xerostomia. The examination started two days before the infusion of hematopoietic stem cells and ended twenty days later. The OM was classified according to the WHO scale and visual analog scale (VAS) was used to measure pain level. Results: Twenty-three individuals were recruted, 83% with malignant diseases and 91% had OM. The median of maximum OM degree was 3 and the maximum pain level was 9. There was a median of 11 days of opioid medication use. The subjects who had the highest mean number of days with mouth pain reached the maximum degree of OM and higher number of days and opiod use. Conclusion: There was a high incidence and high scores of OM, loss of body mass and pain in this sample.


Subject(s)
Humans , Stomatitis/diagnosis , Hematopoietic Stem Cells , Hematology , Medical Oncology , Stem Cells , Stomatitis/drug therapy
18.
S. Afr. med. j. (Online) ; 109(8): 65-70, 2019. ilus
Article in English | AIM | ID: biblio-1271232

ABSTRACT

Autologous and allogeneic haematopoietic stem cell (HSC) transplantation has been performed in patients with various malignant and non-malignant haematological disorders for more than 50 years. Ex vivo gene modification of HSCs for autologous transplantation opens up new therapeutic avenues for genetic and infectious diseases. Major advances have been made over the last three decades with respect to gene modification of HSCs and transplantation strategies, ultimately culminating in the approval of two such therapies in Europe (Strimvelis for a rare primary immune deficiency, and LentiGlobin for beta-thalassaemia). Newer gene-modifying technologies and treatment regimens have also recently come to the fore, which hold great promise for the development of safer and more effective treatments. We provide an overview of the current state of gene-modified HSC therapies, highlighting success stories, limitations and important considerations for achieving successful translation of these therapies to the clinic


Subject(s)
Clinical Laboratory Services , Hematopoietic Stem Cells , Hematopoietic System , Medical Informatics Applications , South Africa , Stem Cell Transplantation
19.
Blood Research ; : 274-281, 2019.
Article in English | WPRIM | ID: wpr-785538

ABSTRACT

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is a well-established treatment modality for a variety of diseases. Immune reconstitution is an important event that determines outcomes. The immune recovery of T cells relies on peripheral expansion of mature graft cells, followed by differentiation of donor-derived hematopoietic stem cells. The formation of new T cells occurs in the thymus and as a byproduct, T cell receptor excision circles (TRECs) are released. Detection of TRECs by PCR is a reliable method for estimating the amount of newly formed T cells in the circulation and, indirectly, for estimating thymic function. The aim of this study was to determine the role of TREC quantitation in predicting outcomes of human leucocyte antigen (HLA) identical allogenic HSCT.METHODS: The study was conducted on 100 patients receiving allogenic HSCT from an HLA identical sibling. TREC quantification was done by real time PCR using a standard curve.RESULTS: TREC levels were inversely related to age (P=0.005) and were significantly lower in patients with malignant diseases than in those with benign diseases (P=0.038). TREC levels could predict relapse as an outcome but not graft versus host disease (GvHD) and infections.CONCLUSION: Age and nature of disease determine the TREC levels, which are related to relapse.


Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Hematopoietic Stem Cells , Humans , Methods , Polymerase Chain Reaction , Real-Time Polymerase Chain Reaction , Receptors, Antigen, T-Cell , Recurrence , Siblings , T-Lymphocytes , Thymus Gland , Transplants
20.
Journal of Experimental Hematology ; (6): 1986-1992, 2019.
Article in Chinese | WPRIM | ID: wpr-781507

ABSTRACT

OBJECTIVE@#To investigate the effect of human placental hematopoietic stem cells (PHSCs) on hematopoietic reconstruction in non-lethally irradiated mice.@*METHODS@#Human placental HSCs were extracted by mechanical method combined with zymolysis and were identified by flow cytometry and colony formationtest. Twenty-five NOG mice were divided randomly into 4 groups: the blank control group (n=5), the irradiated group (n=4), the low dose PHSC group (n=8) and the high dose PHSC group (n=8). The mice in the irradiated, the low dose and the high dose PHSC groups were irradiated with X-rays at dose 1 Gy (100 cGy/min) under sterile condition. The mice in the low dose PHSC group and the high dose PHSC group were injected intravenously with 0.1 ml human placental HSC in dose of 2×10 and 1×10, respectively. The mice in the blank control and the irradiated group were injected with the same volume of saline. The mice were weighed weekly, and the changes of body weight were calculated. The peripheral blood was collected from each group at 4, 8 and 12 week for flow cytometrytic detection of human CD45 and myeloid and lymphoid cells.@*RESULTS@#The flow cytometry and cell-colong formation test showed that the human placental HSC accounted for more than 0.75% of total placental mononuclear cells, moreover possess the differentiation ability. Compared with the blank control group, the relative weight gain in the irradiated, the low dose PHSC, and the high dose PHSC groups decreased significantly, and the relative weight gain in the low dose PHSC and the high dose PHSC group increased significantly as compared with the irradiated group. Flow cytometry showed that at the tine-point of 12 weeks after transplantation, the human blood immune system in the high-dose PHSC mice began long-term reconstruction, while the ratio of human CD45 cells in the low-dose PHSC mice was very low.@*CONCLUSION@#After transplantation of human PHSC the non-lethally irradiated mice can obtain short-term and long-term reconstruetion of human blood cells, which demonstrated that human placental HSC can differentiate and reconstruct hematopoietic function in vivo of irradiated mice.


Subject(s)
Animals , Bone Marrow Cells , Female , Flow Cytometry , Hematopoietic Stem Cell Transplantation , Hematopoietic Stem Cells , Humans , Mice , Mice, Inbred C57BL , Pregnancy
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