Latest Research
All publications from the Cancer3.AI database, newest first.
New insights into JAK2 germline variant-driven stromal cell alterations and proinflammatory bone marrow niche remodeling in myeloproliferative neoplasms.
Nishimura K, et al
Researchers investigated how inherited germline variants in the JAK2 gene influence stromal cells within the bone marrow and contribute to the development of a proinflammatory microenvironment in myeloproliferative neoplasms (MPNs), a group of blood cancers that includes polycythemia vera, essential thrombocythemia, and myelofibrosis. The study found that JAK2 germline variants drive significant alterations in bone marrow stromal cells, reshaping the architecture and inflammatory signaling of the bone marrow niche in ways that promote disease progression. These findings reveal that the pathological process in MPNs extends beyond the malignant blood-forming cells themselves to encompass the surrounding supportive tissue environment. Understanding how the bone marrow niche is remodeled by inherited genetic factors may open new therapeutic avenues targeting not just the cancer cells but also the inflammatory microenvironment that sustains them. For patients and clinicians, these insights underscore the importance of germline genetic background in MPN disease biology and could inform future risk stratification and treatment strategies.
Leukemia
Source →Site-specific methylation of SRSF2P95H by SETD2 inhibits MDSC-mediated proinflammatory niche formation in mouse models of myelodysplastic syndrome.
Li Z, et al
Researchers investigated why patients with myelodysplastic syndrome (MDS) carrying mutations in the SRSF2 gene tend to have poor outcomes and excessive inflammation, focusing on the role of a protein called SETD2. The study found that low SETD2 expression in blood stem cells from these patients correlates with worse prognosis, and that loss of SETD2 in mouse models caused a lethal, hyperinflammatory form of MDS driven by an abnormal expansion of immune-suppressing cells called myeloid-derived suppressor cells (MDSCs). Mechanistically, SETD2 normally adds chemical tags (methyl groups) to two specific sites on the mutant SRSF2 protein, preventing it from causing faulty gene splicing of CEACAM1-4, a molecule that would otherwise ramp up inflammatory IL-1β signaling and fuel MDSC expansion. This cascade creates an immunosuppressive tumor microenvironment that allows the disease to progress unchecked. These findings identify a new molecular signaling axis—SRSF2P95H methylation through SETD2 acting on CEACAM1-4—as a promising therapeutic target for a subset of MDS patients who currently have very limited treatment options.
Science translational medicine
Source →Profiling Ten RHO GTPases in Myeloid Malignancies Reveals Distinct Expression Patterns and Prognostic Associations.
de Almeida Rodrigues B, et al
Researchers investigated the expression of ten RHO GTPase genes — a family of proteins that control cell movement and growth — in bone marrow samples from patients with acute myeloid leukemia (AML) and myelodysplastic neoplasms (MDS), two serious blood cancers. The study found that three genes, RHOBTB2, RND2, and RHOQ, showed abnormal expression levels compared to healthy individuals. Most notably, RHOBTB2 was elevated in both MDS and AML and was strongly associated with worse overall and disease-free survival, including in patients classified as intermediate-risk AML. These findings suggest that RHOBTB2 may play an oncogenic role and could serve as a new prognostic biomarker to help identify AML patients at higher risk of poor outcomes. The research supports further study into RHO GTPases as potential targets and biomarkers in blood cancers, which could ultimately improve patient stratification and treatment decisions.
Cancer medicine
Source →Base-resolution DNA methylome of human MDS hematopoietic stem cell reveals TET2-GFI1 epigenetic axis repressing MDS.
Hu L, et al
Researchers mapped the DNA methylation landscape of hematopoietic stem cells (HSCs) from patients with myelodysplastic syndromes (MDS), a group of bone marrow disorders that can progress to leukemia, at single-base resolution. The study revealed widespread abnormal methylation patterns in MDS HSCs, including hypermethylation in gene-regulatory CpG island regions and hypomethylation in repetitive DNA elements, affecting genes in cancer-related and stem cell function pathways. A key discovery was that loss of TET2, one of the most commonly mutated genes in MDS, causes silencing of the GFI1 gene through promoter hypermethylation, leading to abnormal expansion of stem and progenitor cells — a hallmark of MDS progression. This TET2-GFI1 epigenetic axis was validated in both human MDS samples and mouse models, including TET2-deficient and aged mice, strengthening the evidence for its biological relevance. These findings provide clinicians and researchers with a detailed epigenomic map of MDS stem cells and identify TET2-GFI1 signaling as a potential therapeutic target for correcting HSC dysfunction at its earliest stage.
Immunity & inflammation
Source →Defining remission and relapse after allogeneic hematopoietic cell transplantation in myelodysplastic/myeloproliferative neoplasms and optimization of transplantation outcomes: Recommendations from the EBMT practice harmonisation and guidelines committee.
Armstrong C, et al
A new expert consensus guideline has been developed by the European Society for Blood and Marrow Transplantation (EBMT) to improve care for patients with myelodysplastic/myeloproliferative neoplasms (MDS/MPN), a group of rare and heterogeneous blood cancers. These diseases account for less than 1% of allogeneic hematopoietic cell transplantation (allo-HCT) procedures in Europe annually, and allogeneic transplantation remains the only potentially curative treatment option. The guideline establishes standardized criteria for confirming remission after transplant, including specific timing and thresholds for morphological, molecular, cytogenetic, and chimerism analyses, which will help harmonize data comparisons across international registries. It also provides practical recommendations for managing complications such as poor graft function and splenomegaly, broadly aligned with approaches used in myelofibrosis. The authors highlight that post-transplant relapse remains a major clinical challenge with limited evidence to guide treatment, underscoring an urgent need for collaborative international clinical trials. This framework is intended to standardize post-transplant care, improve patient outcomes, and direct future research efforts in this underserved area of oncology.
Bone marrow transplantation
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