Acute myeloid leukaemia (AML) is a heterogeneous group of diseases with diverse genetic drivers. The conventional one-size-fits-all approach with chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT) has reached an impasse, and only about 40% of patients can achieve long-term survival. Disease heterogeneities have also hampered the development of effective therapy applicable to the multitude of AML subtypes. Recent advances in cancer genetics and genomics have shed light on the genetic underpinnings of AML and both inter-individual and intra-tumoral heterogeneities. These new pieces of knowledge have begun to impact the management and prognostication of AML. They also provide the foundation for personalized treatment for this group of diseases.

Early-onset polyhydramnios during pregnancy can be caused by X-linked transient antenatal Bartter syndrome. Most of the reported cases were molecularly diagnosed after birth, whereas few cases were diagnosed in the fetus period. We received a pregnant woman who had polyhydramnios detected by ultrasound imaging at 25 weeks of gestation, and treated with magnesium sulfate, indomethacin and an amnioreduction at 30 weeks of gestation, whereas amniotic fluid decreased spontaneously since 32 weeks of gestation. Prenatal molecular testing showed the fetus carried MAGED2 hemizygous variant c.967C>T [p. (Asp323*)] inherited from the mother. The preterm boy did not present with polyuria and electrolytes and acid-base imbalance in the early neonatal period, and had good development without polyuria at the age of 20 months. We presented the phenotypes of a Chinese case with a prenatal diagnosis of X-linked transient antenatal Bartter syndrome and his response to prenatal indomethacin treatment. Early identification of the condition helps to provide appropriate prenatal genetic counseling and postnatal management.

Aim: To develop and evaluate genomics education programs for health professionals to expedite the translation of genomics into healthcare.

Methods: Our co-design team of genetic specialists, expert medical specialist peers, and genomics educators developed two continuing genomics education programs for health professionals: stand-alone, specialty-specific workshops and a generic blended learning course, combining online learning with workshops. Both programs referenced adult learning theories; workshops included case-based learning and expert peer-led discussion. Longitudinal surveys evaluated changes in confidence and understanding of genomic testing processes and clinical practice.

Results: We delivered eleven specialty workshops (414 attendees) and a blended learning course comprising four self-directed online modules (61 users) and workshops (71 attendees) for mixed-specialty groups with adult, pediatric, or oncology cases. Surveys (214 workshops; 63 blended) showed that both programs significantly increased confidence and understanding of genomic testing processes. Blended learning participants showed additional gains in confidence after attending a workshop following online learning. Workshop discussions with experts were valued, particularly regarding interpreting and applying results. At follow-up, gains in confidence and understanding were maintained for both programs and 81% of respondents had performed a new genomics activity in clinical practice.

Conclusion: Scalable education is needed. Our results suggest that specialty-specific genomics education may not be required to meet the needs of multiple specialties across a health system. Online learning can meet foundational learning needs but may not be sufficient to apply learning to practice. Blended learning offers flexible, continuing education pathways for dispersed national audiences as genomics becomes increasingly used across varied specialties.

Maintenance of genome integrity is essential for cellular survival. There are mechanisms utilized by the cells to sense and respond to assaults on genomic DNA. These mechanisms are conserved across all domains of life and are collectively called the DNA damage response pathways. However, eukaryotic cells also have extrachromosomal DNA in mitochondria (mtDNA), which is indispensable for mitochondrial function, and hence cell survival. Indeed, impaired mitochondrial activity arising due to mutations in mtDNA has been found to be associated with many human pathologies. Despite its importance, our understanding of how cells ensure mtDNA genome integrity is limited. Since mitochondria do not encode for machinery required for the maintenance of their own genomes, they depend on the nucleus for replication, transcription, and repair processes. This adds a layer of complexity with the requirement for organelle crosstalk and coordination in response to mtDNA damage. This review summarizes recent findings that provide new insights into mechanisms involved in mtDNA quality control, acting at the level of mtDNA or organelle and also discusses a few new avenues of research towards a comprehensive understanding of the “mtDNA damage response”.

Aim: Evidence suggests that the risk of spontaneous preterm birth (sPTB) is the result of environmental exposure interacting with genetic risk and is mediated by epigenetic modification. Long non-coding RNA (lncRNA) comprises a large group of regulators of epigenetic modification that has recently become the focus of increased investigation in reproductive science. Human placenta expresses many lncRNAs, and differential expression profiles (DEPs) have identified several lncRNAs as associated with sPTB. However, little is known about lncRNA’s role in the epigenetic modification of the genes potentially involved in sPTB. This study is to better understand the epigenetic regulation of lncRNA on the development of sPTB.

Methods: A transcriptomic analysis of human placentas derived from various pregnancy outcomes was performed as a discovery study. This was followed by a quantitative confirmation to validate the differential transcription of lncADAM9, the lncRNA overlapping with the ADAM9 gene locus, and of lncRNA-overlapped mRNA of ADAM9 (mRNA-ADAM9). In vitro examination of lncADAM9 transgenic (TG) HTR8 cells were used to perform functional assessment to address the role of lncADAM9-mediated epigenetic regulation of extracellular matrix-adhesion (ECM-A) associated molecules. This assessment was then expanded to studies of human fetal membranes.

Results: We observed that expression of lncADAM9 was increased in sPTB, and this increase was further associated with the down-regulation of mRNA-ADAM9 in human placentas. In vitro, overexpression of lncADAM9 in lncADAM9-transgenic HRT8 cells led to DEPs relevant to ECM-A molecules, particularly at the loci of CNTN1, NRXN2, SPN, ICAM2, and HLA-DPB1. This was also true in fetal membranes from abnormal versus normal fetal membranes.

Conclusion: We have studied the epigenetic impact of differentially expressed lncADAM9 on the ECM-A pathway that is associated with sPTB and documented that this impact may be mediated through the down-regulation of mRNA-ADAM9. Our results of demonstrating the epigenetic regulation of lncADAM9 on the ECM-A pathway may help provide greater insight into critical pathogenic mechanisms underlying sPTB.