Aberrant expression of ecotropic viral integration site-1 (EVI1+) is associated with very poor outcomes in acute myeloid leukemia (AML), mechanisms of which are only partially understood. Using the green fluorescent protein reporter system to monitor EVI1 promoter activity, we demonstrated that Evi1high KMT2A-MLLT1–transformed AML cells possess distinct features from Evi1low cells: the potential for aggressive disease independent of stem cell activity and resistance to cytotoxic chemotherapy, along with the consistent gene expression profiles. RNA sequencing and chromatin immunoprecipitation sequencing in EVI1-transformed AML cells and normal hematopoietic cells combined with functional screening by cell proliferation–related short hairpin RNAs revealed that the erythroblast transformation–specific transcription factor ERG (E26 transformation-specific [ETS]-related gene) and cyclin D1 were downstream targets and therapeutic vulnerabilities of EVI1+ AML. Silencing Erg in murine EVI1+ AML models severely impaired cell proliferation, chemoresistance, and leukemogenic capacity. Cyclin D1 is also requisite for efficient EVI1-AML development, associated with gene expression profiles related to chemokine production and interferon signature, and T- and natural killer–cell exhaustion phenotype, depending on the interferon gamma (IFN-γ)/STAT1 pathway but not on CDK4/CDK6. Inhibiting the IFN-γ/STAT1 pathway alleviated immune exhaustion and impaired EVI1-AML development. Overexpression of EVI1 and cyclin D1 was associated with IFN-γ signature and increased expression of chemokines, with increased exhaustion molecules in T cells also in human AML data sets. These data collectively suggest that ERG and cyclin D1 play pivotal roles in the biology of EVI1+ AML, where ERG contributes to aggressive disease nature and chemoresistance, and cyclin D1 leads to IFN-γ signature and exhausted T-cell phenotypes, which could potentially be targeted.

ChatGPT is gaining widespread acceptance for its ability to generate natural language sentences in response to various inputs and is expected to become a supplementary tool for diagnosing and determining treatment policies in clinical settings. ChatGPT was used to evaluate its ability to perform clinical inference and accuracy in answering questions on the 117th Japanese National Medical Licensing Examination held in February 2023. The exam questions were manually inputted into ChatGPT's window, and the accuracy of ChatGPT's responses was determined based on answers provided by a preparatory school. ChatGPT provided answers for 389 out of 400 questions, and its overall correct answer rate was 55.0%. The correct answer rate for 5-choice-1, 5-choice-2, and 5-choice-3 were 57.8%, 42.9%, and 41.2%, respectively. The highest correct answer rate was for the compulsory exam (67.0%), followed by the specific knowledge exam (54.1%) and the cross category exam (47.9%). The correct answer rate for non-image questions was 56.2% and for image questions, it was 51.5%. The study suggests that ChatGPT has potential to support healthcare professionals in clinical decision-making in Japanese clinical settings, but caution should be exercised in interpreting and using the answers generated by ChatGPT due to room for improvement in performance.

To the Editor: In the review article by Ghanem et al. (Feb. 27 issue)¹ regarding the reemergence of syphilis, information about blood banking is lacking. Transfusion-transmitted syphilis is rare in developed countries, but the recent resurgence of syphilis has had a negative effect on the donor population. The number of cases of syphilis per year in Japan has recently exceeded 6000 for the first time in 50 years, and this number is increasing by 1100 per year.² Unlike other developed countries, Japan has an increase attributed more to heterosexual encounters than to same-sex encounters.³ Women who have one-time heterosexual encounters . . .

To the Editor: The randomized, placebo-controlled trial Benefits and Risks of Iron Interventions in Young Children (BRISC) (September 9 issue)¹ showed that 3 months of iron supplementation in infants reduced the prevalence of anemia but did not improve infant development. Although the daily supplementation with 12.5 mg of elemental iron was consonant with guidelines from the World Health Organization, the increased rates of iron deficiency and anemia seemed higher in the infants who received iron than in those who received placebo, both before and after the subsequent iron-free follow-up period. Table 2 and Table S2 in the Supplementary Appendix indicated . . .