The complex genetic landscape of familial MDS and AML reveals pathogenic germline variants.

The inclusion of familial myeloid malignancies as a separate disease entity in the revised WHO classification has renewed efforts to improve the recognition and management of this group of at risk individuals. Here we report a cohort of 86 acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) families with 49 harboring germline variants in 16 previously defined loci (57%). Whole exome sequencing in a further 37 uncharacterized families (43%) allowed us to rationalize 65 new candidate loci, including genes mutated in rare hematological syndromes (ADA, GP6, IL17RA, PRF1 and SEC23B), reported in prior MDS/AML or inherited bone marrow failure series (DNAH9, NAPRT1 and SH2B3) or variants at novel loci (DHX34) that appear specific to inherited forms of myeloid malignancies.

Are reduced-intensity transplants safe in older patients with hematologic malignancies?

Non-myeloablative allogeneic hematopoietic cell transplantation (HCT) offers a potentially curative therapy for older patients with hematologic malignancies. However, the treatment modality is underutilized and, to date, there are only limited data on outcomes in people older than 60 years. This study describes the toxicities and outcomes of non-myeloablative allogeneic HCT, conditioned with low-dose total body irradiation with or without fludarabine, in patients aged 60-75 years enrolled in prospective multicenter clinical trials.

Isolation and characterization of human interleukin-10-secreting T cells from peripheral blood.

Recent studies have expanded our understanding of the role of the anti-inflammatory cytokine interleukin (IL)-10, produced by multiple lineages of both human and murine T cells, in regulating the immune response. Here, we demonstrate that the small percentage of circulating CD4(+) T cells that secrete IL-10 can be isolated from human peripheral blood and, importantly, we have optimized a protocol to expand these cells in both antigen-specific and polyclonal manners. Expanded CD4(+)IL-10(+) T cells abrogate proliferation and T helper (Th) 1-like cytokine production in an antigen-specific manner, and to a lesser extent exhibit bystander suppressive capacity.