Myelodysplastic Syndrome

P2, N=87, Active, not recruiting, Agios Pharmaceuticals, Inc. | Recruiting --> Active, not recruiting | Trial completion date: Nov 2028 --> Mar 2029 | Trial primary completion date: Nov 2025 --> Mar 2026

P1, N=36, Recruiting, medac GmbH | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Aug 2025 --> Mar 2026

P1/2, N=3, Terminated, National Cancer Institute (NCI) | Completed --> Terminated; Drug company withdrew support.

Despite multiple cycles of azacitidine, within one month, the patient had transitioned into sAML with blasts increased to 55% with heterogeneity in the sample, and TMEM91::TAL1 expression increased to 2.83%...This case illustrates the value of comprehensive molecular profiling, including RNA-seq, in cases of rapidly progressive MDS that cannot be diagnosed through standard molecular diagnostics. The temporal relationship between expression of the fusions and disease progression warrants additional studies of TMEM91::TAL1 in myeloid malignancies.

P1/2, N=84, Not yet recruiting, AstraZeneca | Trial completion date: Jun 2029 --> Feb 2029 | Trial primary completion date: Jun 2029 --> Feb 2029

Newly developed "progenitor scores" based on chromatin accessibility stratify disease status and correlate well with prognosis. These findings indicate that chromatin landscapes of MDS stem cells define their cell-autonomous behavior and contribute to disease progression.

P1, N=94, Not yet recruiting, University of Arizona

The patient responded favourably to the oral prednisolone therapy...Clinicians should be aware of these potential atypical manifestations to prevent delays in the diagnosis and treatment of VEXAS syndrome. Further research is warranted to delineate the full spectrum of clinical and pathological presentations of VEXAS.

Conventional treatments, including chemotherapy and hypomethylating agents +/- venetoclax, offer limited benefit, with high relapse rates and short remissions...Novel therapeutic approaches-ranging from p53 reactivation strategies to immunotherapy and targeted inhibition of specific signaling pathways-are under active investigation. Our review summarizes current knowledge on the molecular pathogenesis, prognostic implications, and therapeutic landscape of TP53-mutated MDS/AML and discusses ongoing challenges and opportunities for improving patient outcomes.

The multifaceted nature of MS necessitates a multidisciplinary approach, including thorough diagnostic evaluation involving immunohistochemistry, cytochemistry, and cytogenetic analysis. Standardizing terminology and refining diagnostic and treatment algorithms through future prospective studies are vital steps toward enhancing clinical management and prognosis for patients with de novo myeloid sarcoma of the urogenital tract.

Iron chelation may modulate disease-relevant redox, endothelial, and cytokine pathways in transfusion-dependent MDS, generating mechanistic hypotheses for prospective clinical validation. These findings support the concept that NTBI reduction mitigates pathogenic processes relevant to disease progression, warranting confirmation in prospective studies integrating clinical endpoints.

Further, in a subset of TP53 -mutant disease, low TCR diversity with skewing toward dominant clonotypes foreshadowed relapse. These findings lay the groundwork for improved relapse prediction and nominate therapeutic targets for early post-transplant intervention.