Sangrado uterino anormal como presentación inicial de malignidades hematológicas / Abnormal uterine bleeding as the initial presentation of hematologic malignancies

El sangrado uterino anormal tiene una etiología variable, que va desde causas estructurales hasta causas funcionales, que se describen clásicamente en el acrónimo PALM-COEIN. No obstante, hay una pobre sensibilización de este síntoma como un marcador de enfermedades graves. En esta revisión se describe la relación de la hemorragia uterina anormal como síntoma clave o de presentación de malignidad hematológica, así como la posible relación con la hemofilia adquirida secundaria a neoplasia hematológica como causal del evento hemostático. Se realizó búsqueda en la literatura, con la mayoría de los artículos obtenidos de Medline, 24 de los cuales cumplieron con los objetivos para resolver la pregunta de investigación. Se encontraron diferentes malignidades hematológicas asociadas a sangrado uterino anormal, de las cuales la hemofilia adquirida y la trombocitopenia como potenciales causales de esta; la mayor correlación fue con leucemia, seguido de linfomas, y en menor cuantía la asociación con mieloma múltiple.

Abnormal uterine bleeding has a variable etiology, ranging from structural to functional causes, classically described by the acronym PALM-COEIN. However, there is poor awareness of this symptom as a marker of serious disease; in this review, we describe the relationship of abnormal uterine bleeding as a key symptom or debut of hematologic malignancy, as well as its possible relationship to acquired hemophilia secondary to hematologic neoplasia as causative of the hemostatic event. A literature search was performed, with most of the articles obtained from Medline, 24 of which met the objectives to solve the research question. Different hematological malignancies associated with abnormal uterine bleeding were found, of which acquired hemophilia and thrombocytopenia were found as potential causes; the highest correlation was with leukemia, followed by lymphomas, and to a lesser extent the association with multiple myeloma.

Periodontal status in adult patients with leukemia: a literature review / Condição periodontal em pacientes adultos com leucemia: revisão de literatura

Periodontal disease is a highly prevalent chronic inflammatory disease that affects the tissues that support the teeth, while leukemia is a type of malignous cancer that affects the production of blood cells. Recent studies suggest that immune response and microbial disbiosis related to periodontal disease may be associated with an increased risk of developing leukemia and may affect its prognosis, as well as leukemia type and treatment may also have effects on the periodontium, demanding a interdiscipinary approach of these patients. The aim of this study was to conduct a literature review to assess the association between periodontal disease and leukemia in adult patients. An electronic database serch using the descriptors was performed. Clinical studies with periodontal examination in adult individuals with leukemia were selected. After literature search, 9 studies were reviewed. Gingival bleeding and periodontal pockets were frequent findings. Periodontitis prevalence varied among studies, ranging from 29% to 82,4% in patients diagnosed with leukemia. The relationship between periodontal disease and leukemia is complex and multifaceted and there are few studies available in adults, with heterogeneous exam protocols. Still, the high prevalence of gingivitis and periodontitis found in the studies suggest that periodontal diagnosis and treatment could be a helpful tool to prevent further complications in leukemia treatment.

A doença periodontal é uma doença inflamatória crônica altamente prevalente e que afeta os tecidos que sustentam os dentes, enquanto a leucemia é um tipo de câncer maligno que afeta a produção de células sanguíneas. Estudos recentes sugerem que a resposta imune e a disbiose microbiana relacionada a doença periodontal podem estar associadas a um risco aumentado de desenvolver leucemia e pode afetar o prognóstico da doença, assim como o tipo de leucemia e o tratamento também podem ter efeitos no periodonto, exigindo uma abordagem interdisciplinar desses pacientes. O objetivo deste estudo foi realizar uma revisão de literatura para avaliar a associação entre doença periodontal e leucemia em pacientes adultos. Foi realizada uma busca eletrônica em bancos de dados utilizando os descritores. Foram selecionados estudos clínicos com exame periodontal em indivíduos adultos com leucemia. Após busca na literatura, 9 estudos foram revisados. Sangramento gengival e bolsas periodontais foram achados frequentes. A prevalência da periodontite variou entre os estudos, sendo de 29% a 82,4% em pacientes diagnosticados com leucemia. A relação entre doença periodontal e leucemia é complexa e multifacetada e existem poucos estudos disponíveis em adultos, com protocolos de exames heterogêneos. Ainda assim, a alta prevalência de gengivite e periodontite encontrada nos estudos sugere que o diagnóstico e o tratamento periodontal podem ser uma ferramenta útil para prevenir maiores complicações no tratamento da leucemia.

Clinical outcome and prognosis of patients with acute myeloid leukemia submitted to chemotherapy with 5 years of follow-up

Abstract Objective The purpose of this study was to evaluate the clinical-epidemiological profile, associated risk factors and clinical outcomes of patients with acute myeloid leukemia (AML), identifying the main causes of morbidity and mortality and overall survival rate of patients at five years of follow-up. Method This was a retrospective cohort study evaluating the prognosis and clinical outcomes of 222 patients diagnosed with AML at three large hematology centers in Ceará (northeastern Brazil) over a period of five years. Results The mean age at diagnosis was 44.1 ± 16 years, with a female prevalence of 1.3:1. No additional relevant risk factors associated with the development of AML were found, except for the well-established cytogenetic assessment. The overall 5-year survival rate was 39.4% (95%CI: 35.47 - 42.17). The main causes of death were disease progression (37.72%; n = 84) and sepsis (31.58%; n = 70). Conclusion The clinical outcomes in our sample of AML patients were similar to those of other reported groups. Disease progression and infection were the main causes of death. Access to diagnostic flow cytometry and karyotyping was greater in our sample than in the national average. As expected, overall survival differed significantly according to the risk, as determined by cytogenetic testing.

Riesgo de mortalidad en candidemia en niños oncohematológicos: revisión sistemática / Mortality risk in candidemia in children with cancer and blood disorders: a systematic review

Introducción: La tasa de mortalidad de la candidemia es variable, pero puede estar influenciada por la patología de base, en especial aquella que condiciona la presencia de neutropenia. En niños con patología oncohematológica, son pocos los trabajos que han abordado la mortalidad relacionada a candidemias y sus factores asociados. Las preguntas que promueven esta revisión sistemática, son: ¿Cuáles son las características epidemiológicas, clínicas y de evolución de los pacientes pediátricos oncohematológicos con candidemia? ¿Cuál es la mortalidad relacionada con esta entidad? Materiales y métodos: Revisión sistemática de la literatura. Se utilizaron los siguientes términos de búsqueda: candidemia por Candida spp. y los siguientes filtros humanos, niños y adolescentes y patología oncohematológica. Se revisaron los artículos publicados en inglés, español o francés hasta el 21 de septiembre de 2023. Las referencias bibliográficas de los artículos incluidos se revisaron manualmente para identificar estudios relevantes adicionales. Resultados: Se encontraron 66 artículos. Del análisis cualitativo realizado en sus textos completos, quedaron finalmente 4 estudios que se consideró que cumplían con los criterios de inclusión. Todos los artículos seleccionados sumaron 191 pacientes con diversas patologías oncohematológicas. La presencia de accesos vasculares fue frecuente en esta serie y la no extracción del catéter venoso central fue el factor más prevalente entre los que fallecieron. El agente infectante predominante fue Candida no albicans y la mortalidad osciló entre el 11,3 y el 31% con una mediana de 25%. No fue posible establecer si la especie de Candida influía en la letalidad

Introduction: The mortality rate of candidemia is variable, but may be influenced by underlying diseases, especially those causing neutropenia. In children with cancer and blood disorders, few studies have addressed mortality related to candidemia and its associated factors. The questions that motivated this systematic review were: What are the epidemiological, clinical and outcome characteristics of pediatric cancer patients with candidemia? What is the mortality related to this condition? Materials and methods: Systematic review of the literature. The following search terms were used: Candida spp., candidemia, with the following filters: human, children and adolescents, and cancer and blood disorders. Articles published in English, Spanish, or French up to September 21, 2023 were reviewed. References of included articles were manually reviewed to identify additional relevant studies. Results: 66 articles were identified. From the qualitative analysis carried out on their full texts, 4 studies that were considered to meet the inclusion criteria were finally selected. The selected articles included a total of 191 patients with various types of cancer and blood disorders. The presence of vascular access was common in this series and failure to remove the central venous catheter was the most prevalent factor among those who died. The predominant infectious agent was non-albicans Candida and mortality ranged from 11.3% to 31% with a median of 25%. It was not possible to establish whether Candida species influenced mortality.

A fase terminal do filho com câncer: percepções dos profissionais hospitalares / The terminal phase of children with cancer: perceptions of hospital professionals / La fase terminal del hijo con cáncer: percepciones de los profesionales del hospital

O confronto com o câncer de um filho e a percepção da sua morte como inevitável dão lugar a experiências parentais relevantes para a pesquisa científica. Este estudo teve como objetivo investigar, por meio da percepção dos profissionais hospitalares, o modo como os pais experienciam a fase terminal e fim de vida do filho com câncer para melhor compreender os processos psicoemocionais experienciados por esses pais diante da cronicidade da doença e da morte do filho. No sentido de alcançar esse objetivo, realizou-se um estudo qualitativo de tipo fenomenológico envolvendo 17 profissionais de dois hospitais portugueses de referência em oncologia pediátrica. Os dados foram recolhidos com recurso a um guia de entrevista semiestruturada. Na percepção dos profissionais hospitalares, os resultados evidenciam que esses pais experienciam múltiplas dificuldades e preocupações na fase terminal da doença do filho e no pós-morte, bem como um sofrimento extremo e desestruturação biopsicossocial e espiritual na família. O conhecimento aprofundado da fenomenologia desses processos é essencial para o desenho e a implementação de intervenções emocionais, cognitivas, comportamentais e sociais mais ajustadas às dificuldades e preocupações parentais vividas no fim de vida e pós-morte.(AU)

Coping with children's cancer and the perception of their inevitable death give rise to parental experiences that are important to study. This study aimed to investigate, based on hospital professionals' perspectives, how parents experience the terminal phase and end of life of their children suffering from cancer to better understand the psycho-emotional processes these parents experienced in face of the chronicity of the disease and their children's death. To achieve this objective, a qualitative phenomenological study was carried out involving 17 professionals of two Portuguese hospitals that are reference in pediatric oncology. Data were collected using a semi-structured interview guide. From the perspective of hospital professionals, results show that these parents experience multiple difficulties and concerns in the terminal phase of their children's disease and postmortem, as well as the extreme suffering and biopsychosocial and spiritual disruption of the family. A deeper understanding of the phenomenology of these processes is essential to design and implement better adjusted emotional, cognitive, behavioral, and social interventions aimed at the parental difficulties and concerns experienced at the end of life and after death.(AU)

El enfrentamiento del cáncer de un hijo y la percepción de su muerte como inevitable dan lugar a experiencias parentales importantes que deben ser estudiadas. Este estudio pretende identificar desde la percepción de los profesionales del hospital cómo los padres viven la fase terminal y el final de la vida de su hijo con cáncer con el fin de comprender mejor los procesos psicoemocionales que viven estos padres ante la cronicidad de la enfermedad y la muerte de su hijo. Para ello, se realizó un estudio cualitativo, con enfoque fenomenológico, en el que participaron 17 profesionales de dos hospitales portugueses de referencia en oncología pediátrica. Para recoger los datos se aplicó un guion de entrevista semiestructurada. En cuanto a la percepción de los profesionales del hospital, estos padres experimentaron múltiples dificultades y preocupaciones en la fase terminal de la enfermedad de su hijo y postmuerte, así como un sufrimiento extremo y una desestructuración biopsicosocial y espiritual en la familia. El conocimiento en profundidad de la fenomenología de estos procesos es esencial para elaborar e implementar intervenciones emocionales, cognitivas, conductuales y sociales más acordes a las dificultades y preocupaciones parentales que se experimentan al final de la vida y la postmuerte.(AU)

Presentación clínica de patologías no malignas que simulan leucemia cutis: a propósito de dos casos / Clinical presentation of non-malignant diseases mimicking leukemia cutis: A report of two cases

La infiltración cutánea por células leucémicas conocida como leucemia cutis es una presentación infrecuente de esta patología y constituye un desafío diagnóstico. Los diagnósticos como infecciones, otras patologías neoplásicas con afectación cutánea y los trastornos histiocíticos, entre otros, constituyen los principales diagnósticos diferenciales, ya que configuran un escenario pronóstico y terapéutico diferente. Se presentan dos pacientes que fueron diagnosticados inicialmente como leucemia cutis, cuyo diagnóstico final fue de patologías no malignas.

The infiltration of leukemia cells into the skin, known as leukemia cutis, is a rare presentation of this disease and accounts for a diagnostic challenge. The main differential diagnoses include infections, other neoplastic diseases with skin involvement and histiocytic disorders, among others, as they entail different prognostic and therapeutic approaches. Here we describe two patients who were initially diagnosed with leukemia cutis, whose final diagnosis was of non-malignant diseases.

Real-world practice of acute leukemia intrathecal chemotherapy administration: A Mexican nationwide survey

ABSTRACT Introduction: Intrathecal chemotherapy is a mainstay component of acute lymphoblastic leukemia treatment. In Mexico, there is a considerable practice variability in aspects, such as the manner of preparation and the administration technique. Objective: Our objective was to describe the different techniques used for the application of ITC and review the existing recommendations in the literature. Method: A cross-sectional, nationwide survey study was conducted by an electronic questionnaire sent to hematologists and oncologists in Mexico. We collected demographic data, personal experience, intrathecal chemotherapy techniques, drug preparation and postprocedural conduct. Results: We received 173 responses. Twenty percent had an anesthesiologist administering sedation and pain management. The platelet count considered safe was 50 × 109/L in 48% of the participants. In 77% (n = 133) of the cases, the conventional needle with stylet used was, 49% did not receive any added diluent in the intrathecal chemotherapy and only 42% were recommended to rest in a horizontal position for more than 30 min. Conclusion: We identified a considerable variation in the administration of intrathecal chemotherapy across the hematologists in Mexico. We discuss the implications and opportunities in reducing the variation in our setting, highlighting the unmet need to establish guidelines that should be evaluated by the Mexican professional society to produce a position paper regarding practice standardization.

Applicability of the acute leukemia (AL) - EBMT score as a prognostic model for allogeneic hematopoietic stem cell transplantation: a single-center, prospective, cohort study at a reference transplant center in Brazil

Abstract Introduction The Acute Leukemia-European Society for Blood and Marrow Transplantation (AL-EBMT) risk score was recently developed and validated by Shouval et al. Objective To assess the ability of this score in predicting the 2-year overall survival (OS-2), leukemia-free survival (LFS-2) and transplant-related mortality (TRM) in acute leukemia (AL) adult patients undergoing a first allogeneic hematopoietic stem cell transplant (HSCT) at a transplant center in Brazil. Methods In this prospective, cohort study, we used the formula published by Shouval et al. to calculate the AL-EBMT score and stratify patients into three risk categories. Results A total of 79 patients transplanted between 2008 and 2018 were analyzed. The median age was 38 years. Acute myeloid leukemia was the most common diagnosis (68%). Almost a quarter of the cases were at an advanced stage. All hematopoietic stem cell transplantations (HSCTs) were human leukocyte antigen-matched (HLA-matched) and the majority used familial donors (77%). Myeloablative conditioning was used in 92% of the cases. Stratification according to the AL-EBMT score into low-, intermediate- and high-risk groups yielded the following results: 40%, 12% and 47% of the cases, respectively. The high scoring group was associated with a hazard ratio of 2.1 (p= 0.007), 2.1 (p= 0.009) and 2.47 (p= 0.01) for the 2-year OS, LFS and TRM, respectively. Conclusion This study supports the ability of the AL-EBMT score to reasonably predict the 2-year post-transplant OS, LFS and TRM and to discriminate between risk categories in adult patients with AL, thus confirming its usefulness in clinical decision-making in this setting. Larger, multicenter studies may further help confirm these findings.

Sobrevida en población pediátrica con leucemia linfoblástica aguda tratada con protocolo ALLIC-BFM de quimioterapia. Revisión sistemática / Survival of pediatric population with acute lymphoblastic leukemia treated with ALLIC-BFM chemotherapy protocol. Systematic review

La leucemia linfoblástica aguda constituye la neoplasia infantil más frecuente. Los tratamientos actuales posibilitan más del 80% de supervivencia libre de enfermedad por cinco años. En el 2000, se probó un protocolo de quimioterapia llamado leucemia linfoblástica intercontinental Berlín-Frankfurt-Münster (ALLIC BFM). El proceso investigativo se realizó mediante la metodología PRISMA, con el propósito de sistematizar la información acerca de la supervivencia de los pacientes pediátricos con leucemia linfoblástica aguda tratados con el uso del protocolo de quimioterapia ALLIC BFM en sus versiones de 2002 o 2009. La supervivencia global en pacientes donde se utilizó el protocolo de 2002 fue del 52% al 91,7% y la libre de enfermedad fue del 45% a 83,3%; mientras que, con el uso del protocolo 2009 se reportó una supervivencia global del 71,1% al 90% y la libre de enfermedad fue del 69,4% al 90,3%. Los principales factores que afectaron la supervivencia fueron las complicaciones relacionadas con el tratamiento, los pacientes de alto riesgo y la medicación insuficiente.

Acute lymphoblastic leukemia is the most common childhood neoplasia. Current treatments allow more than 80% disease-free survival for five years. In 2000, a chemotherapy protocol called Berlin-Frankfurt-Münster intercontinental lymphoblastic leukemia (ALLIC BFM) was tested. The investigative process was carried out using the PRISMA methodology. This study aimed to systematize the information about the survival of pediatric patients with acute lympho-blastic leukemia treated with the ALLIC BFM chemotherapy protocol in its 2002 or 2009 versions. 52% to 91.7% of patients showed an overall survival in patients where the 2002 proto-col was used, and disease-free was from 45% to 83.3%; while, with the use of the 2009 protocol, an overall survival of 71.1% to 90% was reported, and disease-free survival was 69.4% to 90.3%. The main factors affecting survival were treatment-related complications, high-risk patients, and insufficient medication.

Intrathoracic masses in children and adolescents: a single tertiary pediatric institution experience

OBJECTIVES@#The Cancer and Hematology Division of the PCMC receives an average of 24 cases of pediatric intrathoracic masses annually. Comprehensive data on the demographic status, clinical profile, management, and outcome are still not available. This study aims to determine the clinical features, diagnosis, management and outcome of children and adolescents with intrathoracic masses from 2017 to 2019.@*MATERIALS AND METHODS@#Descriptive study design was utilized. Data were collected by doing a chart review. Possible associations between the clinical features and outcome were described.@*RESULTS@#Sixty-eight (68) cases were referred from January 2017 to December 2019. Mean age at diagnosis is 8.8 years with a 2.4:1 male to female ratio. Severe wasting was seen in 21%. All subjects were symptomatic at presentation, 50% with respiratory compromise. Anterior mediastinal lesions are observed at 82% of cases. Elevated LDH was seen in 50% of the patients. Malignant hematologic lesions are the most common etiology. Steroid pretreatment was given in 40% of patients. Only a small percentage (<20%) underwent definitive treatment. Patients were symptomatic for 18 days on average before consult. It took an average of 18 days for a case to be diagnosed definitively, and 10 days from the diagnosis to start of directed treatment. Mortality rate was high at 57.4%@*CONCLUSION@#Patients with intrathoracic mass and malnutrition are 1.4x more likely to die. Diagnosis is the most significant factor associated with death. Observed data can be used as basis to formulate protocols which can streamline the diagnostic and therapeutic approach in these patients.

Clinical and microbiological profile and factors affecting outcome among pediatric febrile neutropenic patients with hematologic malignancies

Objective@#To evaluate the clinical and microbiological profile and factors affecting outcome among pediatric febrile neutropenic (FN) patients with hematologic malignancies (HM)@*Methodology@#This was a cross-sectional study which looked into medical records of Filipino children 0-18years old diagnosed with FN and HM and admitted from June 2016 up to June 2022 at the St. Luke’s Medical Center, Quezon City (SLMC-QC). Data on age, sex, underlying malignancy, stage of treatment, site of infection, presence of central line, initial antibiotic therapy, culture positivity and isolates were retrospectively evaluated. Incomplete records were excluded. The relationship between clinical & microbiologic profile and outcomes were analyzed using T-test and Chi-square test. Significance was set at p<0.05.@*Results@#This study included 267 episodes of FN. Patients had a mean age of 8.3 years with male preponderance (59%). The most frequent underlying malignancy was acute lymphoblastic leukemia (61%). Episodes occurred primarily during the induction (40%) and consolidation phases (28%) of chemotherapy. Most (65%) had an absolute neutrophil count (ANC) of <100/mm3 . Central line catheter was present in 59% of episodes and 52% had an implanted port. There was no identifiable focus of infection in 52% of cases. Gram-negative bacteria, specifically Klebsiella pneumoniae (13%) and Escherichia coli (11%) were the most common isolates. Most patients (88%) recovered. Age >10years, male sex, diagnosis of acute myelogenous leukemia, relapse disease, ANC <100/mm3 , presence of a central line, and central line associated bloodstream infection were significantly associated with duration of hospital stay. Presence of central venous line was the most significant factor associated with mortality. Conclusions: Several clinical and microbiological factors, specifically age >10years, male sex, diagnosis of acute myelogenous leukemia, relapse disease, ANC <100/mm3 , presence of a central line, and central line associated bloodstream infection, were documented to significantly affect outcome in Filipino pediatric FN patients with HM.

Effect of Hispidulin on Proliferation and Apoptosis of Leukemia K562 Cells by Up-Regulating IL-37 / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect and underlying mechanism of hispidulin on the proliferation and apoptosis of leukemia K562 cells.@*METHODS@#K562 cells were cultured in vitro and treated with 0, 5, 25 or 100 μmol/L hispidulin for 24 h. Cell proliferation and apoptosis were detected by CCK-8 and flow cytometry, respectively. Western blot was used to assess the expression of Bax, Bcl-2 and interleukin (IL)-37 proteins. Bone marrow mononuclear cells were extracted from 17 chronic myeloid leukemia patients and 21 healthy individuals by Ficoll-Hypaque density gradient method, and the expression of IL-37 protein was measured by Western blot. K562 cells with IL-37 overexpression or knockdown were constructed, and then treated with 0 or 100 μmol/L hispidulin for 24 h. Cell proliferation, apoptosis and protein expression of Bax and Bcl-2 were determined in the same way as above.@*RESULTS@#After K562 cells were treated with hispidulin, the cell inhibition rate, apoptosis rate, and the protein expression of Bax and IL-37 were significantly increased (P <0.05), but the cell proliferation and expression of Bcl-2 protein were decreased (P <0.05). The expression of IL-37 protein in bone marrow mononuclear cells of the leukemia patient was 0.24±0.03, which was significantly lower than 0.91±0.05 of healthy controls (P <0.05). Overexpression of IL-37 significantly promoted inhibition rate, apoptosis rate, and expression of Bax protein in K562 cells (P <0.05), but suppressed the expression of Bcl-2 protein (P <0.05). In addition, knockdown of IL-37 could reverse the effects of hispidulin on proliferation and apoptosis of K562 cells.@*CONCLUSION@#Hispidulin inhibits the proliferation and induces apoptosis of leukemia K562 cells, which may be related to the up-regulation of IL-37 protein in cells.

Research Progress of Immune Heterogeneity in Leukemia Microenvironment--Review / 中国实验血液学杂志

Although the body has a strong immune system which can resists the invasion of leukemia cells, leukemia cells disseminate systemically and form an immunosuppressive microenvironment through a variety of mechanisms, including regulation of antigen presentation, utilization of immunosuppressive enzyme AXL, immune cell inhibitory checkpoint NKG2A and immunoregulatory gene VISTA, resulting in immune escape. Therefore, most types of leukemia are inevitable for the affliction of drug resistance or relapse, and the immune efficacy is not as significant as that of other hematological tumors and the prognosis is suboptimal. This article reviews the immune heterogeneity of leukemia microenvironment from many aspects, including anti-leukemia immunity and immune escape. In addition, it also reviews the latest progress and future prospects of immune checkpoint inhibition, adoptive cell therapy and vaccine therapy in leukemia, providing a theoretical basis for the development of personalized combination therapy strategies with less toxic side effects.

Comprehensive Diagnosis of Mantle Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To explore the value of multiple detection methods based on histopathology and supplemented by bone marrow or peripheral blood sample detections in the comprehensive diagnosis of mantle cell lymphoma (MCL).@*METHODS@#The clinical, immunophenotypic, pathologic, cytogenetic and molecular features of 153 newly diagnosed MCL patients admitted to the hematology department of our hospital from May 2009 to September 2022 were analyzed.@*RESULTS@#144 (96.6%) of the 149 MCL patients who underwent marrow or peripheral blood IGH/CCND1 FISH detection at initial diagnosis were positive, of which 36 cases (24.2%) had a low proportion positive. The immunophenotypes in 115 patients were analyzed by flow cytometry (FCM), 89 cases (77.4%) conformed to MCL while 23 cases (20.0%) were initially diagnosed as B-cell lymphoproliferative disorders (B-LPD). Of the 75 cases who performed bone marrow biopsy, 50 cases (66.7%) had morphological and immunophenotypic characteristics consistent with MCL, 15 cases (20.0%) were classified as B-LPD, and 10 cases with no obvious abnormality. 77 patients underwent histopathology examination, of which 73 cases (94.8%) had typical clinicopathological features of MCL, including 2 CCND1 negative MCL, 2 pleomorphic variants, 5 pleomorphic variants and 4 cases diagnosed as other leukemia or lymphoma. Among 153 cases of MCL, 128 cases were classic MCL(cMCL), and another 25 cases (16.3%) were diagnosed as leukemic non-lymph node MCL (lnnMCL). The incidence of IGHV mutation, TP53 mutation and CD23 expression positive were significantly different between cMCL and lnnMCL.@*CONCLUSION@#Histopathology is still the main standard for the diagnosis of cMCL, and detection based on bone marrow or peripheral blood samples is an important means for the diagnosis of lnnMCL. Single marker or examination can cause a certain proportion of misdiagnosis. The accurate diagnosis of MCL depends on a combination of multiple detection methods.

MLL1 inhibits the neurogenic potential of SCAPs by interacting with WDR5 and repressing HES1 / 国际口腔科学杂志·英文版

Mesenchymal stem cell (MSC)-based therapy has emerged as a promising treatment for spinal cord injury (SCI), but improving the neurogenic potential of MSCs remains a challenge. Mixed lineage leukemia 1 (MLL1), an H3K4me3 methyltransferases, plays a critical role in regulating lineage-specific gene expression and influences neurogenesis. In this study, we investigated the role and mechanism of MLL1 in the neurogenesis of stem cells from apical papilla (SCAPs). We examined the expression of neural markers, and the nerve repair and regeneration ability of SCAPs using dynamic changes in neuron-like cells, immunofluorescence staining, and a SCI model. We employed a coimmunoprecipitation (Co-IP) assay, real-time RT-PCR, microarray analysis, and chromatin immunoprecipitation (ChIP) assay to investigate the molecular mechanism. The results showed that MLL1 knock-down increased the expression of neural markers, including neurogenic differentiation factor (NeuroD), neural cell adhesion molecule (NCAM), tyrosine hydroxylase (TH), βIII-tubulin and Nestin, and promoted neuron-like cell formation in SCAPs. In vivo, a transplantation experiment showed that depletion of MLL 1 in SCAPs can restore motor function in a rat SCI model. MLL1 can combine with WD repeat domain 5 (WDR5) and WDR5 inhibit the expression of neural markers in SCAPs. MLL1 regulates Hairy and enhancer of split 1 (HES1) expression by directly binds to HES1 promoters via regulating H3K4me3 methylation by interacting with WDR5. Additionally, HES1 enhances the expression of neural markers in SCAPs. Our findings demonstrate that MLL1 inhibits the neurogenic potential of SCAPs by interacting with WDR5 and repressing HES1. These results provide a potential therapeutic target for promoting the recovery of motor function in SCI patients.

Discovery and bioassay of disubstituted β-elemene-NO donor conjugates: synergistic enhancement in the treatment of leukemia / 中国天然药物

Natural products are essential sources of antitumor drugs. One such molecule, β-elemene, is a potent antitumor compound extracted from Curcuma wenyujin. In the present investigation, a series of novel 13,14-disubstituted nitric oxide (NO)-donor β-elemene derivatives were designed, with β-elemene as the foundational compound, and subsequently synthesized to evaluate their therapeutic potential against leukemia. Notably, the derivative labeled as compound 13d demonstrated a potent anti-proliferative activity against the K562 cell line, with a high NO release. In vivo studies indicated that compound 13d could effectively inhibit tumor growth, exhibiting no discernible toxic manifestations. Specifically, a significant tumor growth inhibition rate of 62.9% was observed in the K562 xenograft tumor mouse model. The accumulated data propound the potential therapeutic application of compound 13d in the management of leukemia.

The Effect of Ena/VASP Family on the Expression of GPIb-IX Complex in Human Megakaryoblastic Leukemia Dami Cells / 中国实验血液学杂志

OBJECTIVE@#To explore the effects of Ena/VASP gene family on the expression of glycoprotein (GP) Ib-IX complex in human megakaryoblastic leukemia Dami cells.@*METHODS@#SiRNAs targeting Ena/VASP gene family were designed and synthesized to interfere Enah, EVL and VASP gene expression. When the siRNAs were transfected into Dami cells by using LipofectamineTM 2000 for 48 h, the expression of GPIb-IX complex was detected by quantitative real-time PCR, Western blot and flow cytometry.@*RESULTS@#We successfully established siVASP , siEVL and si Enah Dami cell lines. And it was found that the expression of GPIb-IX complex had no evident reduction in siEVL or siVASP Dami cells at both mRNA and protein level, while the total protein and membrane protein of GPIb-IX complex were obviously reduced when Enah was knocked down.@*CONCLUSION@#Enah could affect the expression of GPIb-IX complex in human megakaryoblastic leukemia Dami cells, but the underlying mechanism still needs to be further explored.