In this week’s episode, we will review a study that utilized whole-genome sequencing to define the mutational spectrum and clonal architecture of myelodysplastic/ myeloproliferative neoplasms, learn more about the association between plasma levels of growth differentiation factor 15 and the risk of venous thromboembolism, and examine the role of microenvironment myeloid cells in supporting the growth of T-cell acute lymphoblastic leukemia.
Lyu et al investigated the role of the microenvironment in T-cell ALL (T-ALL), demonstrating that monocyte-macrophages are necessary for supporting the survival and proliferation of T-ALL cells in vitro and in vivo in murine models. In addition, they demonstrated that an enriched macrophage signature in human pediatric T-ALL is associated with inferior outcomes, suggesting that tumor-associated myeloid cells might offer a novel target for T-ALL therapy.
Myelodysplastic/myeloproliferative (MDS/MPN) neoplasms are a heterogeneous set of syndromes, including chronic myelomonocytic leukemia, atypical chronic myeloid leukemia, MDS/MPN with ring sideroblasts and thrombocytosis, and MDS/MPN unclassifiable (MDS/MPN-U). Using genome-wide sequencing, the authors defined gene signatures underlying genotype-phenotype associations and demonstrated that many patients with MDS/MPN-U have signatures that mimic other subtypes.
Although 85% of pediatric patients with ALL have long-term remission following chemotherapy, the prognosis of relapsed ALL remains poor. Hunger and Raetz use multiple scenarios involving 3 illustrative patients to highlight advances in therapy for relapsed ALL and discuss appropriate sequencing of hematopoietic stem cell transplantation and novel immunotherapies.
Plasma levels of growth differentiation factor 15 are associated with future risk of venous thromboembolism
Growth differentiation factor 15 (GDF-15) is elevated in inflammation and a biomarker for arterial cardiovascular disease. The authors examined the association between GDF-15 and venous thromboembolism (VTE). They demonstrated that elevated plasma levels of GDF-15 are associated with increased VTE risk, with Mendelian randomization suggesting that it is a biomarker of potential VTE risk but not causal.
The bone marrow stem cell niche is critical for hematopoietic stem cell development. The authors demonstrate that vascular endothelial growth factor C (VEGF-C) is critical for maintaining the niche: elimination of VEGF-C leads to delayed hematopoietic recovery posttransplant, and exogenous VEGF-C accelerates hematopoietic recovery from irradiation.