denotes an abstract that is clinically relevant.
denotes that this is a ticketed session.
Description:
In this scientific session, we will explore interactions between normal developmental programs and the abnormal programs that contribute to childhood leukemias or immune deficiency. We will first highlight recent advances in our understanding of normal hematopoietic stem and progenitor cell ontogeny. We will then explore how fetal and neonatal developmental programs can shape the biology of a representative early childhood malignancy: myeloid leukemia of Down Syndrome (ML-DS). Finally, we will explore how maternal stress, such as inflammation or infection, can influence childhood immune development. The cutting-edge science presented here will illuminate mechanisms that critically influence health and well-being.
Dr. Shannon McKinney-Freeman will present an overview of our current understanding of the normal ontogeny of the hematopoietic system during embryogenesis and early life. She will emphasize recent findings that challenge long-held assumptions regarding the developmental origins of hematopoietic progenitors and their transition from embryonic to fetal to adult molecular identities.
Dr. Jan-Henning Klusmann will describe mechanisms underlying ML-DS, a malignancy that arises exclusively in young children with trisomy 21. ML-DS carry pathogomonic mutations in GATA1, and they evolve from antecedent transient abnormal myelopoiesis, a disorder that occurs in 10-30% of neonates with Down Syndrome. The developmentally restricted nature of this malignancy highlights the critical role for fetal/neonatal programming in its pathogenesis. Dr. Klusmann will discuss how RUNX1 isoform shifting during normal fetal ontogeny can sensitize progenitors to GATA1 mutations. He will also discuss the critical, developmentally restricted roles of miR-125b and ARID3A in ML-DS initiation.
Dr. Alan Cantor will describe how inherited GATA1 deficiency can predispose to ML-DS-like leukemias with somatically acquired trisomy or tetrasomy 21. He will highlight the significant phenotypic overlap between these leukemias and ML-DS, including early age of onset. The implications of these findings will be discussed, as they relate to age-specific mechanisms of ML-DS.
Dr. Anna Beaudin will discuss recent findings showing that prenatal inflammation can reprogram fetal hematopoietic progenitor cells, with sustained consequences for postnatal immune function and infection susceptibility. Dr. Beaudin will also highlight new data demonstrating that other types of developmental perturbation, including variation in maternal nutritional status, can program hematopoietic stem cell function into adulthood.
Dr. Shannon McKinney-Freeman will present an overview of our current understanding of the normal ontogeny of the hematopoietic system during embryogenesis and early life. She will emphasize recent findings that challenge long-held assumptions regarding the developmental origins of hematopoietic progenitors and their transition from embryonic to fetal to adult molecular identities.
Dr. Jan-Henning Klusmann will describe mechanisms underlying ML-DS, a malignancy that arises exclusively in young children with trisomy 21. ML-DS carry pathogomonic mutations in GATA1, and they evolve from antecedent transient abnormal myelopoiesis, a disorder that occurs in 10-30% of neonates with Down Syndrome. The developmentally restricted nature of this malignancy highlights the critical role for fetal/neonatal programming in its pathogenesis. Dr. Klusmann will discuss how RUNX1 isoform shifting during normal fetal ontogeny can sensitize progenitors to GATA1 mutations. He will also discuss the critical, developmentally restricted roles of miR-125b and ARID3A in ML-DS initiation.
Dr. Alan Cantor will describe how inherited GATA1 deficiency can predispose to ML-DS-like leukemias with somatically acquired trisomy or tetrasomy 21. He will highlight the significant phenotypic overlap between these leukemias and ML-DS, including early age of onset. The implications of these findings will be discussed, as they relate to age-specific mechanisms of ML-DS.
Dr. Anna Beaudin will discuss recent findings showing that prenatal inflammation can reprogram fetal hematopoietic progenitor cells, with sustained consequences for postnatal immune function and infection susceptibility. Dr. Beaudin will also highlight new data demonstrating that other types of developmental perturbation, including variation in maternal nutritional status, can program hematopoietic stem cell function into adulthood.