Impact of age on the cumulative risk of transformation in patients with chronic myelomonocytic leukaemia

In older patients with chronic myelomonocytic leukaemia (CMML) and limited life expectancy due to age and or comorbidities, it is particularly important to consider the risk of transformation for individualised treatment decisions. There is limited information on potential differences between younger and older CMML patients regarding the cumulative risk of transformation as well as haematological, molecular and biologic characteristics. We analysed data from the Austrian Biodatabase for CMML (ABCMML) to compare these parameters in 518 CMML patients. Categorisation of patients into 3 age‐related groups: <60 years, 60‐79 years and ≥80 years, showed a significantly lower risk of transformation at higher age by competing risk analysis, with a 4‐year risk of 39%, 23% and 13%, respectively (P < .0001). The lower probability of transformation was associated with a lower percentage of blast cells in the peripheral blood (PB) of older patients. Furthermore, we provide a simple score based on age, PB blasts and platelet counts that allowed us to define subgroups of CMML patients with a different cumulative transformation risk, including a low‐risk group with a transformation risk of only 5%. Our findings may facilitate reasonable treatment decisions in elderly patients with CMML

Expansion microscopy: principles and uses in biological research

Many biological investigations require 3D imaging of cells or tissues with nanoscale spatial resolution. We recently discovered that preserved biological specimens can be physically expanded in an isotropic fashion through a chemical process. Expansion microscopy (ExM) allows nanoscale imaging of biological specimens with conventional microscopes, decrowds biomolecules in support of signal amplification and multiplexed readout chemistries, and makes specimens transparent. We review the principles of how ExM works, advances in the technology made by our group and others, and its applications throughout biology and medicine.NIH (Grants 1R01NS102727, 1R01EB024261, 1R41MH112318, 1R01MH110932, 1RM1HG008525, 1DP1NS087724)NSF (Grant 1734870)IARPA (Grant D16PC00008)US Army Research Laboratory & US Army Research Office (Contract W911NF1510548)US–Israel Binational Science Foundation (Grant 2014509

Three-dimensional imaging mass cytometry for highly multiplexed molecular and cellular mapping of tissues and the tumor microenvironment

A holistic understanding of tissue and organ structure and function requires the detection of molecular constituents in their original three-dimensional (3D) context. Imaging mass cytometry (IMC) enables simultaneous detection of up to 40 antigens and transcripts using metal-tagged antibodies but has so far been restricted to two-dimensional imaging. Here we report the development of 3D IMC for multiplexed 3D tissue analysis at single-cell resolution and demonstrate the utility of the technology by analysis of human breast cancer samples. The resulting 3D models reveal cellular and microenvironmental heterogeneity and cell-level tissue organization not detectable in two dimensions. 3D IMC will prove powerful in the study of phenomena occurring in 3D space such as tumor cell invasion and is expected to provide invaluable insights into cellular microenvironments and tissue architecture