KMT2A::MLLT3 acute myelomonocytic leukemia (AML) comes in two clinically and biologically different subtypes. One is characterized by inferior outcome, older age, and MECOM oncogene expression. The other is mainly observed in children and young adults, associates with better clinical outcome, but lacks MECOM. To identify cell fate determining transcription factors downstream of KMT2A::MLLT3, we applied a bioinformatic algorithm that integrates gene and enhancer expression from primary MECOM-positive and -negative KMT2A::MLLT3 AML samples. This identified MECOM to be most influential in the MECOM-positive group, while neuronal transcription factor HMX3 was most influential in the MECOM-negative group. In large AML cohorts, HMX3 expression associated with a unique gene expression profile, younger age (p < 0.002) and KMT2A-rearranged and KAT6A-CREBBP leukemia (p < 0.00001). HMX3 was not expressed in other major genetic risk groups and healthy blood cells. RNA-sequencing analyses following forced HMX3 expression in healthy CD34+ cells and its silencing in KMT2A::MLT3 cells showed that HMX3 drives cancer-associated E2F and MYC gene programs (p < 0.001). HMX3 expression in healthy CD34+ cells blocked monocytic but not granulocytic colony formation. Strikingly, HMX3 silencing in KMT2A::MLLT3 patient cells resulted in cell cycle arrest, monocytic differentiation and apoptosis. Thus, the neuronal transcription factor HMX3 is a leukemia-specific vulnerability in KMT2A::MLLT3 AML.

The transcription factor Growth Factor Independence 1B (GFI1B) recruits Lysine Specific Demethylase 1 A (LSD1/KDM1A) to stimulate gene programs relevant for megakaryocyte and platelet biology. Inherited pathogenic GFI1B variants result in thrombocytopenia and bleeding propensities with varying intensity. Whether these affect similar gene programs is unknow. Here we studied transcriptomic effects of four patient-derived GFI1B variants (GFI1B,,,) in MEG01 megakaryoblasts. Compared to normal GFI1B, each variant affected different gene programs with GFI1B uniquely failing to repress myeloid traits. In line with this, single cell RNA-sequencing of induced pluripotent stem cell (iPSC)-derived megakaryocytes revealed a 4.5-fold decrease in the megakaryocyte/myeloid cell ratio in GFI1B versus normal conditions. Inhibiting the GFI1B-LSD1 interaction with small molecule GSK-LSD1 resulted in activation of myeloid genes in normal iPSC-derived megakaryocytes similar to what was observed for GFI1B iPSC-derived megakaryocytes. Thus, GFI1B and LSD1 facilitate gene programs relevant for megakaryopoiesis while simultaneously repressing programs that induce myeloid differentiation.

Despite a lack of scientific evidence supporting the use of single-sex education, the number of U.S. public schools offering single-sex education has increased. However, our understanding as to why decision-makers have implemented single-sex education is lacking. To address this gap, we surveyed U.S. public-school principals and assessed their attitudes about and experiences with single-sex schooling. Sixty-seven principals from single-sex schools and 193 from coeducational schools participated. The results indicated that principals who had experience with single-sex schooling tended to have more positive attitudes about single-sex schooling, viewed it as more effective, and more often evoked gender-essentialist rationales for the use of single-sex schooling than did coeducational principals. However, both single-sex and coeducational principals noted issues with single-sex schooling. It was concluded that single-sex schooling is not a silver bullet to educational reform and that when single-sex schooling is implemented, one set of issues and problems is substituted for another.

In a state ravaged by suicide and a mental health crisis, this study sought to mitigate impacts of adverse childhood experiences (ACEs) and depressive and anxiety symptomology in high school students in a rural Montana community. Through a seven-week, twice weekly intervention of trauma-informed yoga, participants experienced statistically significant reductions in anxiety (GAD-7) and increases in Strengths and Difficulties (SDQ-11) overall scores and some subscales; noteworthy improvements were also present in depressive symptomatology (PHQ-A), salivary cortisol levels, and sleep duration. Importantly, participant qualitative feedback indicated significant benefits in focus, relaxation, and overall well-being. Further research is needed to imply generalizability and should include a larger, more diverse sample as well as utilization of control groups and an examination of academic and behavioral impacts at the school level.

Studies have sought to understand the underrepresentation of women and racial/ethnic minority groups in STEM, but less attention has been paid to primary school students. Using data from a nationally-representative sample, this study identified factors influencing US third-grade children's self-perceived competencies in math and science, while controlling for their actual abilities. Results indicate that girls had degraded self-perceptions of their math competencies compared to boys, but similar self-rated science competencies. Black students exhibited buoyed self-perceived math competencies, while Hispanic and indigenous students underestimated their science competencies. Students who reported being satisfied with parental attention, friends, and neighborhood had higher self-perceived competencies in both math and science.