Overweight and obesity as predictors of early mortality in Mexican children with acute lymphoblastic leukemia: a multicenter cohort study.

BACKGROUND: Mexico City has one of the highest incidences and mortality rates of acute lymphoblastic leukemia (ALL) in the world and a high frequency of early relapses (17%) and early mortality (15%). Otherwise, childhood overweight and obesity are reaching epidemic proportions. They have been associated with poor outcomes in children with ALL. The aim of present study was to identify if overweight and obesity are predictors of early mortality and relapse in Mexican children with ALL. METHODS: A multicenter cohort study was conducted. ALL children younger than 15 years old were included and followed-up during the first 24 months after diagnosis. Overweight and obesity were classified according World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) criteria. Early mortality and early relapses were the main outcomes. RESULTS: A total of 1070 children were analyzed. Overweight/obesity at diagnosis were predictors of early mortality (WHO: HR = 1.4, 95%CI:1.0-2.0; CDC: HR = 1.6, 95%CI:1.1-2.3). However, no associations between overweight (WHO: HR = 1.5, 95%CI:0.9-2.5; CDC: HR = 1.0; 95% CI:0.6-1.6) and obesity (WHO: HR = 1.5, 95%CI:0.7-3.2; CDC: HR = 1.4; 95%CI:0.9-2.3) with early relapse were observed. CONCLUSIONS: Overweight and obese patients embody a subgroup with high risk of dying during leukemia treatment.

Ethical issues in susceptibility genetic testing for late-onset neurodegenerative diseases.

Genome-wide association studies have revolutionized our understanding of the genetic architecture of complex traits and diseases over the last decade. This knowledge is enabling clinicians, researchers, and direct-to-consumer genetics companies to conduct disease susceptibility testing based on powerful methods such as polygenic risk scoring. However, these technologies raise a set of complex ethical, legal, social, and policy considerations. Here we review and discuss a series of ethical dilemmas associated with susceptibility genetic testing for the two most common late-onset neurodegenerative diseases, Alzheimer's and Parkinson's disease, including testing in asymptomatic individuals. Among others, these include informed consent, disclosure of results and unexpected findings, mandatory screening, privacy and confidentiality, and stigma and genetic discrimination. Importantly, appropriate counseling is a deciding factor for the ethical soundness of genetic testing, which poses a challenge for the regulation of these tests and the training of healthcare professionals. As genetic knowledge about these diseases continues growing and genetic testing becomes more widespread, it is increasingly important to raise awareness among researchers, medical practitioners, genetic counselors, and decision makers about the ethical, legal, and social issues associated with genetic testing for polygenic diseases.

Not only a therapeutic target; mTOR in Hodgkin lymphoma and acute lymphoblastic leukemia.

Introduction: The mechanistic/mammalian target of rapamycin (mTOR) is a serine/threonine kinase, which is downregulated or upregulated and is implicated in different types of cancer including hematologic neoplasms, skin prostate, and head and neck cancer. Aim: The aim of this study was to explore the current knowledge of mTOR signaling in acute lymphoblastic leukemia and Hodgkin lymphoma. Methods: A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searching PubMed, Discovery Service for National Autonomous University of Mexico, Registro Nacional de Instituciones y Empresas Científicas y Tecnológicas (RENIECYT), and Scientific Electronic Library Online (SciELO) from 1994 to 2023. A total of 269 papers were identified for acute lymphoblastic leukemia, but based on specific criteria, 15 were included; for Hodgkin lymphoma, 110 papers were identified, but 5 were included after manual searching. Results: A total of 20 papers were evaluated, where mTOR activity is increased in patients with Hodgkin lymphoma and acute lymphoblastic leukemia by different molecular mechanisms. Conclusions: mTOR activity is increased in patients with both hematologic neoplasms and NOTCH; interleukin 4, 7, and 9, and nuclear proteins have been studied for their role in the activation of mTOR signaling.

Lymphoid progenitor cells from childhood acute lymphoblastic leukemia are functionally deficient and express high levels of the transcriptional repressor Gfi-1.

Acute lymphoblastic leukemia (ALL) is the most frequent malignancy of childhood. Substantial progress on understanding the cell hierarchy within ALL bone marrow (BM) has been recorded in the last few years, suggesting that both primitive cell fractions and committed lymphoid blasts with immature stem cell-like properties contain leukemia-initiating cells. Nevertheless, the biology of the early progenitors that initiate the lymphoid program remains elusive. The aim of the present study was to investigate the ability of lymphoid progenitors from B-cell precursor ALL BM to proliferate and undergo multilineage differentiation. By phenotype analyses, in vitro proliferation assays, and controlled culture systems, the lymphoid differentiation potentials were evaluated in BM primitive populations from B-cell precursor ALL pediatric patients. When compared to their normal counterparts, functional stem and progenitor cell contents were substantially reduced in ALL BM. Moreover, neither B nor NK or dendritic lymphoid-cell populations developed recurrently from highly purified ALL-lymphoid progenitors, and their proliferation and cell cycle status revealed limited proliferative capacity. Interestingly, a number of quiescence-associated transcription factors were elevated, including the transcriptional repressor Gfi-1, which was highly expressed in primitive CD34⁺ cells. Together, our findings reveal major functional defects in the primitive hematopoietic component of ALL BM. A possible contribution of high levels of Gfi-1 expression in the regulation of the stem/progenitor cell biology is suggested.

Clinical features and treatment outcomes of pediatric acute promyelocytic leukemia in a Mexican pediatric hospital.

INTRODUCTION: Acute promyelocytic leukemia (APL) is a distinct type of acute myeloid leukemia (AML) characterized by chromosomal translocations involving the retinoid acid receptor α (RARA) gene on chromosome 17. APL is a relatively rare blood disease that is highly curable with current treatment strategies; however, patient outcomes are heterogeneous in countries with limited resources. Promyelocytic leukemia accounts for 20-25% of all AML cases in Latin American countries. MATERIAL AND METHODS: We conducted a study from July 2007 to July 2012 and applied the IC-APL2006 protocol. This case study reports the results from eleven patients with AML M3 (five males and six females). In all cases, the diagnoses were made by aspirating bone marrow and evaluating the t(15:17) or t(11:17) transcript. In eight cases, the molecular biology-based diagnostics for the PLM-RARa transcript were positive, and they were negative in two cases. One patient was positive for the PLZF-RARa transcript. RESULTS: The mean WBC at the time of diagnosis was 10.1 x 10(9)/L, and the mean platelet count was 17.1 x 10(9)/L. The mean percentage of abnormal promyelocytes in the bone marrow aspirates was 68%. Of the eleven patients, four presented with disseminated intravascular coagulation. All of the patients began treatment with transretinoic acid (ATRA) (45 mg/m(2)/day), which led to 4 cases of ATRA syndrome. There were 2 relapses, and the patient died in one case. The remaining ten patients were alive after the median follow-up period of 33.6 months (range from 11 to 60 months). CONCLUSION: The authors report on a series of cases involving pediatric patients with AML M3 seen at a single institution; the patients were stratified and treated with a standard protocol to obtain satisfactory results. Although the number of patients is limited, the health outcomes are relevant. To our knowledge, this is the first series of pediatric APL patients in Mexico who were treated with the IC-APL2006 protocol.

Fungal infections in pediatric patients with acute myeloid leukemia in a tertiary hospital.

Introduction: Acute leukemia accounts for more than 30% of all pediatric cancer cases, and of these, 15-20% are acute myeloid leukemia (AML). Children who super from AML are more likely to develop infections due to the humoral and cellular immune deficits generated by the disease and its treatment. The incidence of fungal infections is underestimated; reports show that up to 75% of fungal infections go undiagnosed until autopsy. In only 30 years, the incidence of invasive candidiasis has increased by 40-fold. Thus, the high morbidity and mortality associated with fungal infections in hematological patients make it necessary to adopt preventive measures. Methods: This work aimed to retrospectively identify pediatric patients with acute myeloid leukemia and invasive fungal diseases (IFDs) in a Latin American tertiary care hospital. A retrospective analysis of 36 clinical records of pediatric patients diagnosed with AML from 2007 to 2017 was carried out. Results: One hundred and twenty-nine hospitalizations were associated with infectious events. Thirteen patients in our study presented 15 infectious events associated with IFDs (11.6%). Two patients died because of complications related to IFDs (15.3%). The most frequent IFD type was aspergillosis, which was observed in 7 cases, followed by Candidemia, which was observed in 4 cases. The most frequent clinical manifestations were fever and respiratory distress. Discussion: Mortality due to IFD can be prevented with effective pharmacotherapy. An appropriate antifungal prophylaxis strategy still needs to be developed through larger prospective studies in Latin America.

Long-term experience in treatment of acute promyelocytic leukemia in Mexican children in a tertiary care hospital.

Introduction: Acute promyelocytic leukemia (APL) is a rare myeloid leukemia subtype affecting adult and pediatric populations. APL constitutes 15-20% of all childhood AML in Latin America, compared to 7% in the non-Latino population. This leukemia has unique characteristics, such as its association with chromosomal translocations involving the retinoid acid receptor α (RARA) gene on chromosome 17. In addition, APL is also distinct from other AML subtypes due to its response to all-trans-retinoic acid (ATRA), which induces terminal granulocytic differentiation of blasts. Overall 5-year survival rates are generally reported to be greater than 80%. Materials and methods: A study was conducted from January 2008 to December 2022 applying the IC-APL 2006 treatment protocol. This case series reports the clinical results of 22 children with APL. In all cases, the diagnosis was made by bone marrow aspiration and evaluation of the t(15:17) or t(11:17) transcripts. Results: We identified 22 patients with APL, of whom 10 were female and 12 were male. Twelve patients debuted with coagulation abnormalities. The doses of anthracyclines varied according to the risk, with an average of 496.8 mgm2. The cardiological assessment was performed before and after chemotherapy, finding 2/22 patients with moderate sisto-diastolic dysfunction and one with mild pulmonary insufficiency at the end of treatment. There were 6/22 patients with complications related to ATRA treatment, the most frequent being pseudotumor cerebri. All complications were transitory and treated immediately without complications. In this series of cases, an overall survival of 90.6% and a relapse-free survival of 90.6% were recorded. The follow-up mean was 9.1 ± 3.8 years. Conclusion: APL is a highly curable disease when combined with ATRA and anthracyclines. In this series of cases, good long-term results were observed with the IC-APL 2006 protocol. However, in Latin America, the availability of drugs such as arsenic trioxide as the first line of treatment is an unresolved challenge.

A protective maternal nutrient concomitant intake associated with acute leukemia might be modified by sex, in children under 2 years.

Introduction: Maternal dietary consumption during pregnancy has been inconclusively associated with acute leukemia (AL) in infants, probably because epidemiological evidence has emerged mainly from the analysis of one-by-one nutrient, which is not a real-life scenario. Our objective was to evaluate the association between AL in Mexican children under 2 years of age and their mothers' nutrients concomitant intake during pregnancy, as well as to explore whether there are differences between girls and boys. Methods: We conducted a study of 110 cases of AL and 252 hospital-based controls in the Mexico City Metropolitan area from 2010 to 2019. We obtained information on maternal intake of 32 nutrients by a food frequency questionnaire and used weighted quantile sum regression to identify nutrient concomitant intakes. Results: We found a concomitant intake of nutrients negatively associated with AL (OR 0.17; CI95% 0.03,0.88) only among girls; and we did not find a nutrient concomitant intake positively associated with AL. Discussion: This is the first study that suggests nutrients that have been individually associated with AL are not necessarily the same in the presence of other nutrients (concomitant intake); as well as that maternal diet might reduce AL risk only in girls.

Maternal dietary patterns and acute leukemia in infants: results from a case control study in Mexico.

Background: Childhood cancer is the leading cause of disease-related mortality among children aged 5-14 years in Mexico, with acute leukemia being the most common cancer among infants. Examining the overall dietary patterns allows for a comprehensive assessment of food and nutrient consumption, providing a more predictive measure of disease risk than individual foods or nutrients. This study aims to evaluate the association between maternal dietary patterns during pregnancy and the risk of acute leukemia in Mexican infants. Methods: A hospital-based case-control study was conducted, comparing 109 confirmed acute leukemia cases with 152 age-matched controls. All participants (≤24 months) were identified at hospitals in Mexico City between 2010 and 2019. Data on a posteriori dietary patterns and other relevant variables were collected through structured interviews and dietary questionnaires. Multivariate logistic regression was employed to estimate the association between maternal dietary patterns during pregnancy and the risk of acute leukemia in infants. Results: The "Balanced & Vegetable-Rich" pattern, characterized by a balanced consumption of various food groups and higher vegetable intake, exhibited a negative association with acute leukemia when compared to the "High Dairy & Cereals" Pattern (adjusted odds ratio [OR] = 0.51; 95% confidence interval [CI]: 0.29, 0.90). We observed that mothers who gave birth to girls and adhered to a healthy dietary pattern during pregnancy exhibited significantly lower odds of their children developing AL compared to those who gave birth to boys [OR = 0.32 (95% CI 0.11, 0.97)]. Our results underscore the significance of maternal nutrition as a modifiable factor in disease prevention and the importance of prenatal health education.

Predictors of Septic Shock or Bacteremia in Children Experiencing Febrile Neutropenia Post-Chemotherapy.

BACKGROUND: Febrile neutropenia (FN) is an early indicator of infection in oncology patients post-chemotherapy. We aimed to determine clinical predictors of septic shock and/or bacteremia in pediatric cancer patients experiencing FN and to create a model that classifies patients as low-risk for these outcomes. METHODS: This is a retrospective analysis with clinical data of a cohort of pediatric oncology patients admitted during July 2015 to September 2017 with FN. One FN episode per patient was randomly selected. Statistical analyses include distribution analysis, hypothesis testing, and multivariate logistic regression to determine clinical feature association with outcomes. RESULTS: A total of 865 episodes of FN occurred in 429 subjects. In the 404 sampled episodes that were analyzed, 20.8% experienced outcomes of septic shock and/or bacteremia. Gram-negative bacteria count for 70% of bacteremias. Features with statistically significant influence in predicting these outcomes were hematological malignancy (P < .001), cancer relapse (P = .011), platelet count (P = .004), and age (P = .023). The multivariate logistic regression model achieves AUROC = 0.66 (95% CI 0.56-0.76). The optimal classification threshold achieves sensitivity = 0.96, specificity = 0.33, PPV = 0.40, and NPV = 0.95. CONCLUSIONS: This model, based on simple clinical variables, can be used to identify patients at low-risk of septic shock and/or bacteremia. The model's NPV of 95% satisfies the priority to avoid discharging patients at high-risk for adverse infection outcomes. The model will require further validation on a prospective population.

Mortality in children with cancer and SARS-CoV-2 in Latin America: A systematic review.

The new COVID-19 disease is caused by a novel coronavirus (SARS-CoV-2), that probably originated in Wuhan, China, and has currently infected 505,817,953 people and caused 6,213,876 deaths in the world. On the American continent, 152,265,980 cases and 2,717,108 deaths have been reported to WHO (World Health Organization). The Latin America and the Caribbean (LAC) region presents an epidemiological challenge due to its population's heterogeneity and socioeconomic inequality. A particularly vulnerable population is that of children with cancer, and their mortality from COVID-19 has been reported to be 3.6% globally. This work aimed to study the lethality of SARS-CoV-2 infection in children with cancer in the Latin American region. Our objective was to systematically review published scientific literature and search hospital databases in Latin America to explore mortality in this region. A median of mortality of 9.8% was found in the articles analyzed. In addition, we collected five databases from Latin American hospitals. We concluded that there was an underestimation in the mortality registry of this group of patients in the analyzed region. Therefore, although the causes are unknown, it is necessary to strengthen the case-reporting system to determine the reality in complex and particular areas such as Latin America.

Childhood acute leukemias are frequent in Mexico City: descriptive epidemiology.

BACKGROUND: Worldwide, acute leukemia is the most common type of childhood cancer. It is particularly common in the Hispanic populations residing in the United States, Costa Rica, and Mexico City. The objective of this study was to determine the incidence of acute leukemia in children who were diagnosed and treated in public hospitals in Mexico City. METHODS: Included in this study were those children, under 15 years of age and residents of Mexico City, who were diagnosed in 2006 and 2007 with leukemia, as determined by using the International Classification of Childhood Cancer. The average annual incidence rates (AAIR), and the standardized average annual incidence rates (SAAIR) per million children were calculated. We calculated crude, age- and sex-specific incidence rates and adjusted for age by the direct method with the world population as standard. We determined if there were a correlation between the incidence of acute leukemias in the various boroughs of Mexico City and either the number of agricultural hectares, the average number of persons per household, or the municipal human development index for Mexico (used as a reference of socio-economic level). RESULTS: Although a total of 610 new cases of leukemia were registered during 2006-2007, only 228 fit the criteria for inclusion in this study. The overall SAAIR was 57.6 per million children (95% CI, 46.9-68.3); acute lymphoblastic leukemia (ALL) was the most frequent type of leukemia, constituting 85.1% of the cases (SAAIR: 49.5 per million), followed by acute myeloblastic leukemia at 12.3% (SAAIR: 6.9 per million), and chronic myeloid leukemia at 1.7% (SAAIR: 0.9 per million). The 1-4 years age group had the highest SAAIR for ALL (77.7 per million). For cases of ALL, 73.2% had precursor B-cell immunophenotype (SAAIR: 35.8 per million) and 12.4% had T-cell immunophenotype (SAAIR 6.3 per million). The peak ages for ALL were 2-6 years and 8-10 years. More than half the children (58.8%) were classified as high risk. There was a positive correlation between the average number of persons per household and the incidence of the pre-B immunophenotype (Pearson's r, 0.789; P = 0.02). CONCLUSIONS: The frequency of ALL in Mexico City is among the highest in the world, similar to those found for Hispanics in the United States and in Costa Rica.

Human, mouse, and dog bone marrow show similar mesenchymal stromal cells within a distinctive microenvironment.

Bone marrow stromal cells (BMSCs) are a key part of the hematopoietic niche. Mouse and human BMSCs are recognized by different markers (LepR and NGFR/CD271, respectively). However, there has not been a detailed in situ comparison of both populations within the hematopoietic microenvironment. Moreover, dog BMSCs have not been characterized in situ by any of those markers. We conducted a systematic histopathological comparison of mouse, human, and dog BMSCs within their bone marrow architecture and microenvironment. Human and dog CD271+ BMSCs had a morphology, frequency, and distribution within trabecular bone marrow similar to those of mouse LepR+ BMSCs. However, mouse bone marrow had higher cellularity and megakaryocyte content. In conclusion, highly comparable bone marrow mesenchymal stromal cell distribution among the three species establishes the validity of using mouse and dog as a surrogate experimental model of hematopoietic stem cell-BMSC interactions. However, the distinct differences in adipocyte and megakaryocyte microenvironment content of mouse bone marrow and how they might influence hematopoietic stem cell interactions as compared with humans require further study.

Survival in pediatric patients with cancer during the COVID-19 pandemic: scoping systematic review.

Background: Coronavirus disease (COVID)-19 has currently affected 8,015,502 million people worldwide with global mortality around 5%. Information in pediatric cancer patients is still limited, but it is emerging day by day. The objective of this scoping review was to analyze the available data associated with COVID-19 infection and mortality in pediatric cancer patients and to provide useful information to plan and design strategies in this group. Methods: A search was conducted, and eight articles were obtained for qualitative analysis; 110 patients were included, all from cross-sectional studies. At the time of publication, all the analyzed documents reported no deaths associated with COVID-19. Results: According to the information, COVID-19 infection appears to be less severe in the pediatric population in comparison with adults and does not appear to be a cause of mortality in patients with childhood cancer. Conclusions: Given the nature of preliminary reports and a short follow-up in cancer patients, it is necessary to have medium- and long-term follow-up studies to determine the effects of infection and modifications to the treatments of these patients.

Introducción: La enfermedad conocida como COVID-19 ha afectado ya a 8,015,502 millones de personas en el mundo, con una mortalidad global de aproximadamente el 5%. La información en pacientes pediátricos con cáncer es aún limitada y está surgiendo día a día. El objetivo de esta revisión sistemática fue conocer los datos disponibles sobre la COVID-19 y la mortalidad en los pacientes pediátricos con cáncer, y aportar información útil para planear y diseñar estrategias en este grupo. Métodos: Se llevó a cabo una búsqueda y se seleccionaron ocho artículos para realizar un análisis cuantitativo; se incluyeron 110 pacientes, todos provenientes de estudios transversales. Al momento de las publicaciones, no se documentaron fallecimientos asociados a la COVID-19 en los documentos analizados. Resultados: De acuerdo con la información de esta revisión sistemática, la COVID-19 parece ser menos grave que en los adultos y no parece ser causa de mortalidad en pacientes pediátricos con cáncer. Conclusiones: Dada la naturaleza de los reportes preliminares y el corto seguimiento en los pacientes con cáncer, es necesario contar con estudios de seguimiento a mediano y largo plazo para conocer los efectos de la infección y de las modificaciones del tratamiento en estos pacientes.

Survival and Complications in Pediatric Patients With Cancer and COVID-19: A Meta-Analysis.

BACKGROUND: The pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected all age groups, including the pediatric population, in 3-5% of all cases. We performed a meta-analysis to understand the survival and associated complications in pediatric cancer patients as well as their hospitalization, intensive care, and ventilation care (supplemental oxygen/endotracheal intubation) needs. METHODS: A systematic search was performed using MEDLINE, TRIP Database, International Clinical Trials Registry Platform (WHO), The Cochrane Library, Wiley, LILACS, and Google Scholar. Additionally, a search using the snowball method was performed in Nature, New England Journal of Medicine, Science, JAMA, ELSEVIER editorial, Oxford University Press, The Lancet, and MedRxiv. Searches were conducted until July 18, 2020. A total of 191 cancer patients with coronavirus disease 2019 (COVID-19) were integrated from 15 eligible studies. In a sub-analysis, patients were stratified into two groups: hematological cancer and solid tumors. Outcome measures were overall survival, risk of hospitalized or needing intensive care, and need for ventilatory support in any modality. The random effects statistical analysis was performed with Cochran's chi square test. The odds ratio (OR) and heterogeneity were calculated using the I2 test. RESULTS: The overall survival was 99.4%. There were no statistically significant differences in the risk of hospitalization between hematological malignancies and solid tumors (95% confidence interval [CI] 0.48-18.3; OR = 2.94). The risk of being admitted to the intensive care unit was also not different between hematological malignancies and other tumors (95% CI 0.35-5.81; OR = 1.42). No differences were found for the need of ventilatory support (95% CI 0.14-3.35; OR = 0.68). Although all the studies were cross-sectional, the mortality of these patients was 0.6% at the time of analysis. CONCLUSIONS: In the analyzed literature, survival in the studied group of patients with COVID-19 was very high. Suffering from hematological neoplasia or other solid tumors and COVID-19 was not a risk factor in children with cancer for the analyzed outcomes.

Aberrant immunophenotypes in acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is the most prevalent hematologic neoplasia worldwide. To classify leukemia, we analyzed the immunophenotypic characteristics in the neoplastic cells obtained with antibodies by cell flow cytometry or immunohistochemistry. The aberrant immunophenotypes are antigen expression patterns that differ from the normal hematopoietic maturation process, which can include some different lineage antigens such as myeloid antigens in ALL or asynchronous expression of antigens. These aberrant immunophenotypes have been studied as prognostic factors and residual disease markers. In this review, some aspects of aberrant immunophenotypes are addressed, including definition, epidemiology, and potential uses.

La leucemia linfoblástica aguda es la neoplasia hematológica más prevalente en el mundo. Para clasificar la leucemia se utilizan características inmunofenotípicas en las células neoplásicas que se pueden observar con anticuerpos en la citometría de flujo o mediante inmunohistoquímica. Los inmunofenotipos aberrantes son los patrones de expresión de los antígenos que difieren del proceso normal de maduración hematopoyética, y pueden incluir antígenos de linajes diferentes, como antígenos mieloides en la leucemia linfoblástica aguda, o la expresión asincrónica de antígenos. Estos inmunofenotipos aberrantes se han estudiado como factores de pronóstico y como marcadores de enfermedad mínima residual. En esta revisión se abordan algunos aspectos de los inmunofenotipos aberrantes, incluyendo su definición, epidemiología y usos potenciales.

Acute myeloid leukemia associated with t(16:21)(p11;q22) in a pediatric patient.

Background: Background">Rare subgroups of pediatric patients with acute myeloid leukemia (AML), such as t(16:21) (p11;q22), require international cooperation to establish a proper stratification system to assign clinical risk. Case report: Here, we report a 13-year-old female who was admitted for asthenia, fatigue, and intermittent fever. The hematological data showed thrombocytopenia and anemia, and the bone marrow test showed 82.5% blast cells, which were positive for CD13, CD33, CD38, and CD117. Blast cells showed negative myeloperoxidase staining and positive periodic acid-Schiff staining. A diagnosis of AML M6 was made. Cells were positive for the fusion transcript FUS-ERG t(16;21)(p11;q22). The patient achieved morphological remission. However, molecular remission was not achieved, and she died 11 months after diagnosis. Conclusions: It is essential to report this sporadic case of AML to provide clinicians with data for clinical decision-making, such as for risk-group stratification. To the best of our knowledge, this is the first association between this translocation and this morphological subtype.

Introducción: La leucemia mieloide aguda (LMA) infantil es una enfermedad heterogénea, por lo que existen subgrupos de rara presentación, como aquellos con t(16;21)(p11;q22). Para establecer el riesgo clínico y la estratificación pronóstica adecuada es necesaria la cooperación internacional. Caso clínico: Se reporta el caso de una adolescente de 13 años, admitida por astenia, adinamia y fiebre intermitente. Los datos hematológicos mostraron trombocitopenia y anemia, con un 82.5% de blastos en médula ósea, los cuales fueron positivos para CD13, CD33, CD38 y CD 117. Los blastos fueron negativos para mieloperoxidasa y positivos para ácido peryódico de Schiff. Se realizó el diagnóstico morfológico de LMA M6. Las células fueron positivas para el transcrito FUS-ERG t(16;21)(p11;q22). La paciente alcanzó la remisión morfológica; sin embargo, no fue posible la remisión molecular y falleció 11 meses después del diagnóstico. Conclusiones: Es importante reportar casos en los que se identifique un subtipo muy raro de LMA infantil para incrementar la evidencia clínica y contribuir con elementos que ayuden a tomar decisiones clínicas y lograr la estratificación en grupos de riesgo. Hasta la fecha, este el primer caso reportado en que se asocia el transcrito t(16;21)(p11;q22) con el subtipo morfológico LMA M6.

High cortactin expression in B-cell acute lymphoblastic leukemia is associated with increased transendothelial migration and bone marrow relapse.

Cancer is a major cause of death in children worldwide, with B-lineage cell acute lymphoblastic leukemia (B-ALL) being the most frequent childhood malignancy. Relapse, treatment failure and organ infiltration worsen the prognosis, warranting a better understanding of the implicated mechanisms. Cortactin is an actin-binding protein involved in cell adhesion and migration that is overexpressed in many solid tumors and in adult B-cell chronic lymphocytic leukemia. Here, we investigated cortactin expression and potential impact on infiltration and disease prognosis in childhood B-ALL. B-ALL cell lines and precursor cells from bone marrow (BM) and cerebrospinal fluid (CSF) of B-ALL patients indeed overexpressed cortactin. In CXCL12-induced transendothelial migration assays, transmigrated B-ALL cells had highest cortactin expression. In xenotransplantation models, only cortactinhigh-leukemic cells infiltrated lungs, brain, and testis; and they colonized more easily hypoxic BM organoids. Importantly, cortactin-depleted B-ALL cells were significantly less efficient in transendothelial migration, organ infiltration and BM colonization. Clinical data highlighted a significant correlation between high cortactin levels and BM relapse in drug-resistant high-risk B-ALL patients. Our results emphasize the importance of cortactin in B-ALL organ infiltration and BM relapse and its potential as diagnostic tool to identify high-risk patients and optimize their treatments.