Management of children and adolescents with chronic myeloid leukemia in chronic phase: International pediatric chronic myeloid leukemia expert panel recommendations.

The treatment strategy for children and adolescents with chronic myeloid leukemia in the chronic phase (CML-CP) has evolved from allogeneic hematopoietic stem cell transplantation (HSCT) to tyrosine kinase inhibitors (TKIs). With the advent of next-generation TKIs and new targeted therapies in the CML field, an international pediatric CML expert panel provides recommendations based on the medical literature (including previous pediatric guidelines), national standards, and treatment principles used in adults with CML-CP. Recommendations include diagnosis of the disease and details on managing the initial steps of care of children and adolescents with newly diagnosed CML-CP, including complications such as leukostasis.

Case report: A rare case of intragastric metastasis after liver transplantation for liver cancer.

A 13-year-old boy was admitted to Xiang'an Hospital of Xiamen University due to HBV-related liver cancer. Intrahepatic metastasis was considered to occur by CT scan. A gastroscope revealed esophagogastric variceal bleeding, and later, the patient underwent a successful liver transplantation.

Pentraxin-3 modulates hepatocyte ferroptosis and the innate immune response in LPS-induced liver injury.

The liver plays a crucial role in the immune response during endotoxemia and is one of the critical targets for sepsis-related injuries. As a secretory factor involved in inflammation, pentraxin-3 (PTX3) has been demonstrated to regulate hepatic homeostasis; however, the relationship between PTX3 and cell crosstalk between immune cells and hepatocytes in the liver remains incompletely understood. In this study, we revealed that, compared with WT mice, Ptx3 mice with lipopolysaccharide (LPS)-induced endotoxemia exhibited alleviated liver damage, with reduced serum alanine transaminase and aspartate transaminase levels and an improved survival rate.

The impact of SARS-CoV-2 infection on immunity reconstitution among pediatric patients after allogeneic hematopoietic stem cell transplantation: a propensity score-matched analysis.

Background: Immunity reconstitution (IR) is crucial for pediatric patients undergoing hematopoietic stem cell transplantation (HSCT), but the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on lymphocyte subsets post-transplant remains unclear. Therefore, we assessed immune cell dynamics in children after SARS-CoV-2 infection.

Methods: We enrolled 42 children, including 21 post-HSCT SARS-CoV-2 infected and 21 matched, non-infected historical controls (1:1 matching based on propensity scores).

Encephalitozoon hellem infection after haploidentical allogeneic hematopoietic stem cell transplantation in children: a case report.

Background: Encephalitozoon hellem (E. hellem) infection is a zoonotic disease, rarely observed in individuals, causing various clinical manifestations including diarrhea, keratoconjunctivitis, cystitis, etc. E.

Jak2V617F Reversible Activation Shows Its Essential Requirement in Myeloproliferative Neoplasms.

Unlabelled: Gain-of-function mutations activating JAK/STAT signaling are seen in the majority of patients with myeloproliferative neoplasms (MPN), most commonly JAK2V617F. Although clinically approved JAK inhibitors improve symptoms and outcomes in MPNs, remissions are rare, and mutant allele burden does not substantively change with chronic therapy. We hypothesized this is due to limitations of current JAK inhibitors to potently and specifically abrogate mutant JAK2 signaling.

Iron chelation improves ineffective erythropoiesis and iron overload in myelodysplastic syndrome mice.

Myelodysplastic syndrome (MDS) is a heterogeneous group of bone marrow stem cell disorders characterized by ineffective hematopoiesis and cytopenias, most commonly anemia. Red cell transfusion therapy for anemia in MDS results in iron overload, correlating with reduced overall survival. Whether the treatment of iron overload benefits MDS patients remains controversial.

Direct identification of pathogens via microbial cellular DNA in whole blood by MeltArray.

Rapid identification of pathogens is critical for early and appropriate treatment of bloodstream infections. The various culture-independent assays that have been developed often have long turnaround times, low sensitivity and narrow pathogen coverage. Here, we propose a new multiplex PCR assay, MeltArray, which uses intact microbial cells as the source of genomic DNA (gDNA).

MSI2 deficiency in ILC3s attenuates DSS-induced colitis by affecting the intestinal microbiota.

Background: The etiology and pathogenesis of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are generally believed to be related to immune dysfunction and intestinal microbiota disorder. However, the exact mechanism is not yet fully understood. The pathological changes associated with dextran sodium sulfate (DSS)-induced colitis are similar to those in human UC.

Immune microenvironment infiltration landscape and immune-related subtypes in prostate cancer.

Background: The tumor microenvironment (TME) primarily comprises cancer cells, cancer-infiltrating immune cells, and stromal cells. The tumor cells alter the TME by secreting signaling molecules to induce immune tolerance. The immune cell infiltrating the TME influences the prognosis of patients with cancers.

Phenotypic and genotypic correlation evaluation of 148 pediatric patients with Fanconi anemia in a Chinese rare disease cohort.

Background: Fanconi anemia (FA) is a rare autosomal recessive, X-linked or autosomal dominant disease. Few large-scale FA investigations of rare disease cohorts have been conducted in China.

Methods: We enrolled 148 patients diagnosed with FA according to evidence from the clinical phenotype, family history, and a set of laboratory tests.

Genotype-guided model significantly improves accuracy of tacrolimus initial dosing after liver transplantation.

Background: The initial dose of tacrolimus after liver transplantation (LT) is critical for rapidly achieving the steady state of the drug concentration, minimizing the potential adverse reactions and warranting long-term patient prognosis. We aimed to develop and validate a genotype-guided model for determining personalized initial dose of tacrolimus.

Methods: By combining pharmacokinetic modeling, pharmacogenomic analysis and multiple statistical methods, we developed a genotype-guided model to predict individualized tacrolimus initial dose after LT in the discovery (n = 150) and validation cohorts (n = 97) respectively.

Genetic factors underlying tacrolimus intolerance after liver transplantation.

Background: Tacrolimus (FK506) is the cornerstone of immunosuppression after liver transplantation (LT), however, clinically, switching from FK506 to cyclosporine (SFTC) is common in LT patients with tacrolimus intolerance. The aim of this study was to investigate the genetic risk of patients with tacrolimus intolerance.

Methods: A total of 114 LT patients were enrolled in this retrospective study.

DNAH2 facilitates the homologous recombination repair of Fanconi anemia pathway through modulating FANCD2 ubiquitination.

Fanconi anemia (FA), an X-linked genetic or autosomal recessive disease, exhibits complicated pathogenesis. Previously, we detected the mutated Dynein Axonemal Heavy Chain 2 () gene in 2 FA cases. Herein, we further investigated the potential association between DNAH2 and the homologous recombination repair pathway of FA.

Therapeutic Efficacy of Combined JAK1/2, Pan-PIM, and CDK4/6 Inhibition in Myeloproliferative Neoplasms.

Purpose: The JAK1/2 inhibitor ruxolitinib has demonstrated significant benefits for patients with myeloproliferative neoplasms (MPN). However, patients often lose response to ruxolitinib or suffer disease progression despite therapy with ruxolitinib. These observations have prompted efforts to devise treatment strategies to improve therapeutic efficacy in combination with ruxolitinib therapy.

Sfxn1 is essential for erythrocyte maturation via facilitating hemoglobin production in zebrafish.

Previous reports revealed that mutation of mitochondrial inner-membrane located protein SFXN1 led to pleiotropic hematological and skeletal defects in mice, associated with the presence of hypochromic erythroid cell, iron overload in mitochondrion of erythroblast and the development of sideroblastic anemia (SA). However, the potential role of sfxn1 during erythrocyte differentiation and the development of anemia, especially the pathological molecular mechanism still remains elusive. In this study, the correlation between sfxn1 and erythroid cell development is explored through zebrafish in vivo coupled with human hematopoietic cells assay ex vivo.

[The Correlation of Minimal Residual Disease with Prognosis in TCF3-PBX1 Acute Lymphoblastic Leukemia in Children].

Objective: To investigate the consistency between FCM and PCR on the detecting of MRD in TCF3-PBX1 ALL, and to investigate the prognosis value of these 2 methods.

Methods: 55 cases of paediatric TCF3-PBX1 ALL patients from April 2008 to April 2015 were enrolled and analyzed. The FCM and PCR was used to detect the MRD in 239 bone marrow samples of 55 patients.

[Clinical features and gene mutation spectrum in children with sideroblastic anemia].

Objective: To study the clinical features and gene mutation spectrum of children with sideroblastic anemia (SA) and the clinical value of targeted next-generation sequencing in the molecular diagnosis of children with SA.

Methods: Clinical data were collected from 36 children with SA. Targeted next-generation sequencing was used to detect mutations in SA-related pathogenic genes and genes associated with heme synthesis and mitochondrial iron metabolism.

[Clinical features of Wiskott-Aldrich syndrome: an analysis of 13 cases].

Objective: To study the clinical features of Wiskott-Aldrich syndrome (WAS) in children.

Methods: A retrospective analysis was performed for the clinical data of 13 children with WAS.

Results: All 13 children were boys, with a median age of onset of 3 months (range 1-48 months) and a median age of 24 months (range 1-60 months) at the time of diagnosis.

Role of cytarabine in paediatric acute promyelocytic leukemia treated with the combination of all-trans retinoic acid and arsenic trioxide: a randomized controlled trial.

Background: The combination of all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) has been suggested to be safe and effective for adult acute promyelocytic leukaemia (APL). As of 2010, the role of cytarabine (Ara-C) in APL was controversial. The aim of this study was to test the efficacy and safety of ATRA and ATO in paediatric APL patients.

Intron 1 GATA site enhances ALAS2 expression indispensably during erythroid differentiation.

The first intronic mutations in the intron 1 GATA site (int-1-GATA) of 5-aminolevulinate synthase 2 (ALAS2) have been identified in X-linked sideroblastic anemia (XLSA) pedigrees, strongly suggesting it could be causal mutations of XLSA. However, the function of this int-1-GATA site during in vivo development remains largely unknown. Here, we generated mice lacking a 13 bp fragment, including this int-1-GATA site (T AGATAA: AGCCCC) and found that hemizygous deletion led to an embryonic lethal phenotype due to severe anemia resulting from a lack of ALAS2 expression, indicating that this non-coding sequence is indispensable for ALAS2 expression in vivo Further analyses revealed that this int-1-GATA site anchored the GATA site in intron 8 (int-8-GATA) and the proximal promoter, forming a long-range loop to enhance ALAS2 expression by an enhancer complex including GATA1, TAL1, LMO2, LDB1 and Pol II at least, in erythroid cells.