Differentially expressed genes (adjusted P <0.01 ) in STAG2/LMO2 subtype compared to other T-ALL cases.

Differentially expressed genes (adjusted P <0.05) in three TLX3 subtypes (TLX3 γδ, TLX3 immature, TLX3 DP-like) compared to other T-ALL cases.

The gene expression profiles of γδ T-ALL.

Compounds used in single-dose (10uM) drug screening.

Differential peaks of H3K27ac and differentially expressed genes in gene-edited PF382 model.

The list of drugs for the patient-derived xenografts (PDX) cell screening.

Comparison of clinical characteristics and outcomes between gamma delta T-ALL and non-gamma delta T-ALL.

Lists of T-ALL related genes for filtering tumor-only and RNAseq samples.

Patient characteristics of 24 cases of STAG2/LMO2 subtype T-ALL that were performed genomic analysis.

The clinical features of γδ T-ALL.

Patient characteristics of 76 γδ T-ALL cases performed genomic analysis.

Up-regulated pathways in STAG2/LMO2 subtype compared to other T-ALL cases for mouse leukemia initiating cells (LIC) signatures analyzed by gene-set enrichment analysis (GSEA).

BACKGROUND:ATP-binding cassette transporter A3 (ABCA3) deficiency is a rare form of interstitial lung disease caused by biallelic pathogenic variants in ABCA3, it is the most common cause of genetic surfactant deficiency among European and US infants and children. This study aimed to elucidate the genetic features of ABCA3 deficiency in Japanese children. MATERIALS AND METHODS:From April 2011 to March 2024, 291 candidates with children's interstitial lung disease (chILD) were enrolled. Sanger sequencing or next-generation sequencing for ABCA3 was performed for all candidates. RESULTS:Eleven cases of ABCA3 deficiency were identified, including one pair of siblings. Among eight cases with onset at birth, five-including the siblings-died. All three cases whose disease onset occurred after 1 yr of age survived, and no cases presented between 1 month and 1 yr of age. Of the 11 cases, nine carried compound heterozygous ABCA3 variants. In the remaining two cases, diagnosed as ABCA3 deficiency based on specific pathological findings, only one pathogenic variant was detected in each. No homozygous variants were found, and aside from the siblings, no cases shared the same pathogenic variants. Eighteen distinct pathogenic variants were identified, including nine missense, five nonsense, three splicing, and one frameshift variant. All were considered disease-causing. DISCUSSION:The incidence of ABCA3 deficiency among chILD candidates (11/291, 3.8%) was significantly lower (p < 0.0001) than those reported in the United States (185/632, 29.3%), Europe (79/398, 19.8%) and Argentina (14/50, 28%). The frequency of ABCA3 deficiency among Japanese children is low.

PURPOSE:Male childhood cancer survivors (CCS) are at increased risk of hypogonadism, which may be overlooked due to subtle symptoms. Early detection of male hypogonadism remains challenging. In Japan, lacking a nationwide surveillance system for gonadal dysfunction in CCS, few studies focus on male CCS. This study aimed to prospectively identify compensated primary hypogonadism (cPH) among male CCS using a comprehensive medical checkup system. METHODS:We prospectively recruited CCS aged 18 and older who had been diagnosed with pediatric cancer over 10 years ago and untreated for more than 5 years. Physical checkup and mental health examination were conducted for both CCS and healthy CCS siblings, and analyzed data from male participants. We defined cPH if their testicular volume was 10 mL or lower and/or the follicle-stimulating hormone level was greater than 10 IU/L. RESULTS:Among 30 CCS aged 19-41, 12 were identified as having cPH. Factors significantly associated with cPH in CCS included receiving a cyclophosphamide equivalent dose greater than 7.5 g/m2, experiencing secondary cancers, and older age at medical checkup. CCS with cPH exhibited higher fasting blood sugar and elevated luteinizing hormone levels. Furthermore, CCS with cPH reported significantly lower mental component summary scores and reported greater psychological distress. CONCLUSION:Despite the limited sample size, our preliminary findings suggest that this surveillance approach may help identify male CCS at risk for hypogonadism. These survivors warrant monitoring for gonadal dysfunction and associated complications.

Models for examining the effects of STAG2 inactivation.