Potential value of high-throughput single-cell DNA sequencing of Juvenile myelomonocytic leukemia: report of two cases.

Juvenile myelomonocytic leukemia (JMML) is a rare myeloproliferative disease of early childhood that develops due to mutations in the genes of the RAS-signaling pathway. Next-generation high throughput sequencing (NGS) enables identification of various secondary molecular genetic events that can facilitate JMML progression and transformation into secondary acute myeloid leukemia (sAML). The methods of single-cell DNA sequencing (scDNA-seq) enable overcoming limitations of bulk NGS and exploring genetic heterogeneity at the level of individual cells, which can help in a better understanding of the mechanisms leading to JMML progression and provide an opportunity to evaluate the response of leukemia to therapy. In the present work, we applied a two-step droplet microfluidics approach to detect DNA alterations among thousands of single cells and to analyze clonal dynamics in two JMML patients with sAML transformation before and after hematopoietic stem cell transplantation (HSCT). At the time of diagnosis both of our patients harbored only "canonical" mutations in the RAS signaling pathway genes detected by targeted DNA sequencing. Analysis of samples from the time of transformation JMML to sAML revealed additional genetic events that are potential drivers for disease progression in both patients. ScDNA-seq was able to measure of chimerism level and detect a residual tumor clone in the second patient after HSCT (sensitivity of less than 0.1% tumor cells). The data obtained demonstrate the value of scDNA-seq to assess the clonal evolution of JMML to sAML, response to therapy and engraftment monitoring.

First-principles study of graphenylene/MoX2 (X = S, Te, and Se) van der Waals heterostructures.

New van der Waals (vdW) heterostructures obtained by stacking monolayers of recently synthesized graphenylene (Gr) and two-dimensional 1H-MoX2 (X = S, Te, and Se) are proposed and analyzed using ab initio calculations. These heterostructures are stable under normal conditions and have unique crystalline lattices. The study of electronic properties shows that the proposed materials are direct-gap semiconductors with a narrow band gap, which can be controlled by in-plane tensile strain or a transverse electric field. The considered vdW heterostructures demonstrate the transition of band alignments between types I, II and III, when in-plane stress or a transverse electric field is applied, and hold great potential for creating multifunctional devices for stretched electronics. Computations based on the non-equilibrium Green's function method indicate a high rectification factor of the order of 103-104 for a diode based on the Gr/MoS2 vdW junction. The studied structures exhibit broad optical absorption across the entire visible range and represent a promising material for optoelectronic applications.