A CADASIL NOTCH3 mutation leads to clonal hematopoiesis and expansion of Dnmt3a-R878H hematopoietic clones.

Clonal hematopoiesis (CH) is nearly universal in the elderly. The molecular and cellular mechanisms driving CH and the clinical consequences of carrying clonally derived mutant mature blood cells are poorly understood. We recently identified a C223Y mutation in the extracellular domain (ECD) of NOTCH3 as a putative CH driver in mice.

Turning the spotlight on bone marrow adipocytes in haematological malignancy and non-malignant conditions.

Whilst bone marrow adipocytes (BMAd) have long been appreciated by clinical haemato-pathologists, it is only relatively recently, in the face of emerging data, that the adipocytic niche has come under the watchful eye of biologists. There is now mounting evidence to suggest that BMAds are not just a simple structural entity of bone marrow microenvironments but a bona fide driver of physio- and pathophysiological processes relevant to multiple aspects of health and disease. Whilst the truly multifaceted nature of BMAds has only just begun to emerge, paradigms have shifted already for normal, malignant and non-malignant haemopoiesis incorporating a view of adipocyte regulation.

Diversity in the bone marrow niche: Classic and novel strategies to uncover niche composition.

Our view on the role and composition of the bone marrow (BM) has dramatically changed over time from a simple nutrient for the bone to a highly complex multicellular tissue that sustains haematopoiesis. Among these cells, multipotent haematopoietic stem cells (HSCs), which are predominantly quiescent, possess unique self-renewal capacity and multilineage differentiation potential and replenish all blood lineages to maintain lifelong haematopoiesis. Adult HSCs reside in specialised BM niches, which support their functions.