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T‐cell acute lymphoblastic leukemia (T‐ALL) is a rare and aggressive hematological malignancy primarily affecting adolescents and young adults and is scarce in infants and toddlers under age 3. Unlike B‐ALL, T‐ALL in this young population remains poorly characterized due to limited data and lacks evidence‐based guidelines to help clinicians determine the optimal treatment approach. In this study, we conducted a comprehensive genetic analysis of infant/toddler T‐ALL cases from a French national cohort, utilizing high‐throughput targeted sequencing, optical genome mapping, and RNA sequencing. Genetic analysis revealed the absence of TLX1/3 dysregulation. Instead, we identified a significant prevalence of NKX2 rearrangements (n = 9, 33%), co‐occurring with MYB alterations (n = 5/9) or chromothripsis‐like events (n = 3/9). Additional findings included TAL1/‐like anomalies (30%), STAG2::LMO2 (15%), ETS rearrangements (15%), and rarely, KMT2A rearrangements (7%). Comparative analyses with 245 patients aged 3–18 years, enrolled in the pediatric FRALLE2000T French protocol, underscored the distinct clinical and genetic profiles of infants/toddlers. Despite presenting with higher rates of hyperleukocytosis and slower responses to treatment, they demonstrated comparable survival outcomes to older pediatric patients, with a 5‐year overall survival (OS) rate of 75.4% (95% confidence interval [CI]: 60.0%–94.8%) versus 75.2% (95% CI: 69.8%–81.1%), p = 0.86. Notably, alterations in NKX2, KMT2A, and STAG2::LMO2 delineated oncogenic subgroups exhibiting a remarkable 100% OS rate, while patients with TAL1 or ETS dysregulation experienced less favorable outcomes. This was further supported by analyses of data from the COG AALL0434 trial, enhancing our understanding of T‐ALL in infants/toddlers. Large‐scale collaborative studies remain essential to confirm these findings and refine treatment strategies.

The contribution of γδ T cells to immune responses is associated with rapid secretion of interferon-γ (IFN-γ). Here, we show a perinatal thymic wave of innate IFN-γ-producing γδ T cells that express CD8αβ heterodimers and expand in preclinical models of infection and cancer. Optimal CD8αβ + γδ T cell development is directed by low T cell receptor signaling and through provision of interleukin (IL)-4 and IL-7. This population is pathologically relevant as overactive, or constitutive, IL-7R–STAT5B signaling promotes a supraphysiological accumulation of CD8αβ + γδ T cells in the thymus and peripheral lymphoid organs in two mouse models of T cell neoplasia. Likewise, CD8αβ + γδ T cells define a distinct subset of human T cell acute lymphoblastic leukemia pediatric patients. This work characterizes the normal and malignant development of CD8αβ + γδ T cells that are enriched in early life and contribute to innate IFN-γ responses to infection and cancer. Here the authors identify and characterize the development and function of an IFN-γ-producing CD8αβ + subset of γδ T cells that contributes to malignancy.

Peripheral T cell lymphomas (PTCLs) represent a significant unmet medical need with dismal clinical outcomes. The T cell receptor (TCR) is emerging as a key driver of T lymphocyte transformation. However, the role of chronic TCR activation in lymphomagenesis and in lymphoma cell survival is still poorly understood. Using a mouse model, we report that chronic TCR stimulation drove T cell lymphomagenesis, whereas TCR signaling did not contribute to PTCL survival. The combination of kinome, transcriptome, and epigenome analyses of mouse PTCLs revealed a NK cell-like reprogramming of PTCL cells with expression of NK receptors (NKRs) and downstream signaling molecules such as Tyrobp and SYK. Activating NKRs were functional in PTCLs and dependent on SYK activity. In vivo blockade of NKR signaling prolonged mouse survival, demonstrating the addiction of PTCLs to NKRs and downstream SYK/mTOR activity for their survival. We studied a large collection of human primary samples and identified several PTCLs recapitulating the phenotype described in this model by their expression of SYK and the NKR, suggesting a similar mechanism of lymphomagenesis and establishing a rationale for clinical studies targeting such molecules.

We aimed to assess the popularity and perceived effectiveness of smartphone tools that track and limit smartphone use. We also aimed to explore how a set of variables related to mental health, smartphone use, and smartphone addiction may influence the use of these tools. First, we conducted a web-based survey in a representative sample of 1989 US-based adults using the crowdsourcing platform Prolific. Second, we used machine learning and other statistical tools to identify latent user classes; the association between latent class membership and demographic variables; and any predictors of latent class membership from covariates such as daily average smartphone use, social problems from smartphone use, smartphone addiction, and other psychiatric conditions. Smartphone tools that monitor and control smartphone use were popular among participants, including parents targeting their children; for example, over two-thirds of the participants used sleep-related tools. Among those who tried a tool, the highest rate of perceived effectiveness was 33.1% (58/175). Participants who experienced problematic smartphone use were more likely to be younger and more likely to be female. Finally, 3 latent user classes were uncovered: nonusers, effective users, and ineffective users. Android operating system users were more likely to be nonusers, whereas younger adults and females were more likely to be effective users. The presence of psychiatric symptoms did not discourage smartphone tool use. If proven effective, tools that monitor and control smartphone use are likely to be broadly embraced. Our results portend well for the acceptability of mobile interventions in the treatment of smartphone-related psychopathologies and, potentially, non–smartphone-related psychopathologies. Better tools, targeted marketing, and inclusive design, as well as formal efficacy trials, are required to realize their potential.

Objective Despite the availability of thousands of mental health applications, the extent to which they are used and the factors associated with their use remain largely unknown. The present study aims to (a) assess in a representative US-based population sample the use of smartphone apps for mental health and wellbeing (SAMHW), (b) determine the variables predicting the use of SAMHW, and (c) explore how a set of variables related to mental health, smartphone use, and smartphone “addiction” may be associated with the use of SAMHW. Methods Data was collected via online questionnaire from 1989 adults. The data gathered included information on smartphone use behavior, mental health, and the use of SAMHW. Latent class analysis was used to categorize participants. Machine learning and logistic regression analyses were used to determine the most important predictors of SAMHW use and associations between predictors and outcome variables. Results While two-thirds of participants had a statistically high probability for using SAMHW, nearly twice more had high probability for using them to improve wellbeing compared to using them to address mental health problems (43% vs. 18%). In both groups, these participants were more likely to be female and in the younger adult age bracket than male and in the adult or older adult age bracket. According to the machine learning model, the most important predictors for using the relevant smartphone apps were variables associated with smartphone problematic use, COVID-19 impact, and mental health problems. Conclusion Findings from the present study confirm that the use of SAMHW is growing, particularly among younger adult and female individuals who are negatively impacted by problematic smartphone use, COVID-19, and mental health problems. These individuals tend to bypass traditional care via psychotherapy or psychopharmacology, relying instead on smartphones to address mental health conditions or improve wellbeing. Advising users of these apps to also seek professional help and promoting efforts to prove the efficacy and safety of SAMHW would seem necessary.