[Genetic and clinical characteristics of children with -mutated juvenile myelomonocytic leukemia].

Objectives: To investigate the genomic characteristics and prognostic factors of juvenile myelomonocytic leukemia (JMML) with mutations.

Methods: A retrospective analysis was conducted on the clinical data of JMML children with mutations treated at the Hematology Hospital of Chinese Academy of Medical Sciences, from January 2008 to November 2022.

Results: A total of 34 children were included, with 17 cases (50%) having isolated mutations, 9 cases (27%) having isolated mutations, and 8 cases (24%) having compound mutations.

Engineered CRO-CD7 CAR-NK cells derived from pluripotent stem cells avoid fratricide and efficiently suppress human T-cell malignancies.

Background: T-cell malignancies are highly aggressive hematological tumors with limited effective treatment options. CAR-NK cell therapy targeting CD7 has emerged as a promising approach for treating T-cell malignancies. However, conventional CAR-NK cell therapy faces the challenges of cell fratricide due to CD7 expression on both malignant cells and normal NK cells.

Homoharringtonine in Relapsed/Refractory Paediatric T-Cell Acute Lymphoblastic Leukaemia-A Case Series and a Report on the Use of In Vitro Drug Profiling.

Paediatric relapse/refractory T-cell acute lymphoblastic leukaemia (T-ALL) is notoriously difficult to treat. This group of heavily pre-treated patients needs effective agents that can rapidly control the disease while not having significant toxicity. Homoharringtonine (HHT) has been widely used in children with acute myeloid leukaemia, but there is little information on T-ALL.

Single-cell epigenetic and clonal analysis decodes disease progression in pediatric acute myeloid leukemia.

Pediatric acute myeloid leukemia (pAML) is a clonal disease with recurrent genetic alterations that affect epigenetic states. However, the implications of epigenetic dysregulation in disease progression remain unclear. Here, we interrogated single-cell and clonal level chromatin accessibility of bone marrow samples from 28 patients with pAML representing multiple subtypes using mitochondrial single-cell assay for transposase-accessible chromatin with sequencing, which revealed distinct differentiation hierarchies and abnormal chromatin accessibility in a subtype-specific manner.

[Establishment of BCL-2 Inhibitors-Resistant B-cell Acute Lymphoblastic Leukemia Cell Lines and Study on Their Resistance Mechanisms].

Objective: RS4;11 cell line was used to establish BCL-2 inhibitor-resistant cell lines of B-cell acute lymphoblastic leukemia (B-ALL) and explore the possible mechanisms of drug resistance.

Methods: RS4;11 cell line was continuously induced and cultured by low and ascending concentrations of BCL-2 inhibitors navitoclax and venetoclax to construct navitoclax-resistant cell line RS4;11/Nav and venetoclax-resistant cell line RS4;11/Ven. The cell viability was detected by MTT assay, and the cell apoptosis was detected by flow cytometry.

Single-cell transcriptomic analysis of the immune microenvironment in pediatric acute leukemia.

Relapse and treatment resistance pose significant challenges in the management of pediatric B cell acute lymphoblastic leukemia (B-ALL) and acute myeloid leukemia (AML). The efficacy of immunotherapy in leukemia remains limited due to factors such as the immunosuppressive tumor microenvironment (TME) and lack of suitable immunotherapeutic targets. Thus, an in-depth characterization of the TME in pediatric leukemia is warranted to improve the efficacy of immunotherapy.

Single-cell analysis highlights a population of Th17-polarized CD4 naïve T cells showing IL6/JAK3/STAT3 activation in pediatric severe aplastic anemia.

Acquired aplastic anemia (AA) is recognized as an immune-mediated disorder resulting from active destruction of hematopoietic cells in bone marrow (BM) by effector T lymphocytes. Bulk genomic landscape analysis and transcriptomic profiling have contributed to a better understanding of the recurrent cytogenetic abnormalities and immunologic cues associated with the onset of hematopoietic destruction. However, the functional mechanistic determinants underlying the complexity of heterogeneous T lymphocyte populations as well as their correlation with clinical outcomes remain to be elucidated.

Dasatinib-therapy induced sustained remission in a child with refractory TCF7-SPI1 T-cell acute lymphoblastic leukemia.

The prognosis of patients with T-cell acute lymphoblastic leukemia (T-ALL) has been largely lacked behind than that of patients with B-cell ALL, especially in refractory or relapsed cases. Here, we describe a 4.7-year-old male child with TCF-SPI1-postitve T-ALL who developed refractoriness disease after a seven drugs-conventional therapy.

Necrosulfonamide reverses pyroptosis-induced inhibition of proliferation and differentiation of osteoblasts through the NLRP3/caspase-1/GSDMD pathway.

The acute inflammatory stimulation occurring after a bone fracture regulates the repair and healing of local bone injury; however, under certain conditions, pyroptosis may occur in osteoblasts, which affects osteoblast proliferation and differentiation, thereby affecting the growth, development and morphological changes of bone tissue. The aim of the present study was to examine the effect of the pyroptosis inhibitor necrosulfonamide (NSA) on the proliferation and differentiation of osteoblasts and elucidate the underlying mechanism. The results revealed that NSA reversed the effects of ATP/lipopolysaccharide (LPS) on cell viability and pyroptosis, and on the mRNA and protein expression of pyroptosis-related genes.

Long-term outcomes of 172 children with severe aplastic anemia treated with rabbit antithymocyte globulin and cyclosporine.

This study retrospectively analyzed the clinical outcome of 172 children with newly diagnosed severe aplastic anemia (SAA) between January 2008 and April 2018, who received rabbit antithymocyte globulin (ATG) and cyclosporine (CsA) as first-line treatment. The median age at diagnosis was 5 years (range, 1-14). The overall response rates were 22.