The developmental origins of health and disease (DOHaD) indicate that fetal tissues and organs in critical and sensitive periods of development are susceptible to structural and functional changes due to the adverse environment in utero. Maternal immune activation (MIA) is one of the phenomena in DOHaD. Exposure to maternal immune activation is a risk factor for neurodevelopmental disorders, psychosis, cardiovascular diseases, metabolic diseases, and human immune disorders. It has been associated with increased levels of proinflammatory cytokines transferred from mother to fetus in the prenatal period. Abnormal immunity induced by MIA includes immune overreaction or immune response failure in offspring. Immune overreaction is a hypersensitivity response of the immune system to pathogens or allergic factor. Immune response failure could not properly fight off various pathogens. The clinical features in offspring depend on the gestation period, inflammatory magnitude, inflammatory type of MIA in the prenatal period, and exposure to prenatal inflammatory stimulation, which might induce epigenetic modifications in the immune system. An analysis of epigenetic modifications caused by adverse intrauterine environments might allow clinicians to predict the onset of diseases and disorders before or after birth.

Images in Clinical Medicine from The New England Journal of Medicine — Gastric Gyri — Pediatric Ménétrier’s Disease

Acute myeloid leukaemia (AML) is a haematologic malignancy with high relapse rates in both adults and children. Leukaemic stem cells (LSCs) are central to leukaemopoiesis, treatment response and relapse and frequently associated with measurable residual disease (MRD). However, the dynamics of LSCs within the AML microenvironment is not fully understood. This study utilized three-dimensional cellular automata (CA) modelling to simulate LSC behaviour and treatment response under induction chemotherapy. Our study revealed: (i) a correlation between LSC persistence post-induction chemotherapy and risk of AML relapse; (ii) MRD negativity based on LSC count may not reliably predict outcomes, supporting clinical evidence that patients with MRD-negative status can still be at risk of relapse; (iii) prolonged persistence of LSCs post-chemotherapy without disruption of normal haematopoiesis, aligning with clinical observations of dormant AML clones; (iv) early LSC dynamics post-induction chemotherapy, characterized by stochastic behaviours and movement velocities, are insufficient predictors of long-term prognosis; and (v) a distinct spatiotemporal organization of LSCs in later phases post-induction chemotherapy is correlated with long-term outcomes. Our modelling results provide a theoretical and clinical framework for AML research, and future clinical data validation could refine the utility of CA modelling for oncological studies.