RUNX1 (RUNX Family Transcription Factor 1)

Serial assessments were performed before and during treatment with bortezomib and dexamethasone for MM, and later with daunorubicin/cytarabine for AML. It demonstrates the earliest events in pDC-AML evolution. Furthermore, the immature immunophenotype raises the question of appropriate treatment, since a diagnosis of acute undifferentiated leukemia can be established.

Current research has revealed that ASXL1 mutations in MDS predict demethylating agents (HMAs) resistance, the combination of HMAs and Venetoclax (VEN) achieved an ORR of 87%. DNMT3A R882 mutations induce decitabine sensitivity via hemi-methylated enhancer trapping, and TET2 mutations enhance HMAs efficacy only in ASXL1 wild-type contexts (ORR 62.1% vs. co-mutated 19%). RUNX1 aberrations reduce chemotherapy responses (18.9% ORR in high-risk MDS) through DNA repair impairment, while BCOR/EZH2 loss drives cytarabine resistance. TP53 multi-hit lesions correlate with poor survival (OS <12 months) but respond to eprenetapopt-azacitidine (ORR 73%), and IDH1/2 inhibitors achieve durable remissions (ivosidenib ORR 83.3%, mOS 35.7 months). In this paper, we systematically illustrate the correlation between key gene mutations and the response to HMAs, chemotherapy and targeted therapies in MDS patients. This article summarizes the current evidence on gene mutations as predictive biomarkers and discusses the direction of individualized therapy.

Subsequent comprehensive integration of clinical history, repeated bone marrow assessment, cytogenetics, fluorescence in situ hybridization (FISH), and extended immunohistochemistry(IHC) revealed the tumor to be a myeloid sarcoma (MS), representing an extramedullary relapse of his underlying AML. This case underscores the diagnostic pitfalls of MS, particularly within the central nervous system (CNS), and highlights the critical importance of considering MS in patients with a history of AML, especially those with genetic profiles predisposing to extramedullary disease, even when pathology initially suggests lymphoma.

The high diagnostic coverage and rapid turnaround of the FISH-based approach underscore its value as a reliable and efficient diagnostic tool in newly diagnosed ALL. The authors have confirmed clinical trial registration is not needed for this submission.

P2, N=147, Recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2025 --> May 2029 | Trial primary completion date: Oct 2025 --> May 2029

Space-time clustering at birth and diagnosis was observed in the HeH subgroup, suggesting potential etiologic heterogeneity in BCP-ALL. These findings support further investigation of environmental and infectious exposures across immunophenotypes and genetic subtypes in larger cohorts.

No amplifications or deletions were seen. This genomic landscape study highlights significant genomic differences between KMT2Ar and KMT2Awt AML patients, which may enrich our understanding of the molecular profile and clusters of mutations in AML.

Furthermore, NKX2-1 positive cells showed less induction of DNA damage and apoptosis upon treatment with etoposide, a DNA damaging chemotherapy agent that is clinically used to treat T-ALL...Notably, NKX2-1 expressing cells showed higher sensitivity towards RUNX1 inhibition, suggesting a cooperative role in regulating T-ALL cell survival. This work reveals a critical role of NKX2-1 in enhancing T-ALL cell survival through DNA damage protection, and identifies RUNX1 as an important cofactor in T-ALL pathogenesis.

The overall survival of MDS patients with ASXL1mut is poor. The patients with p.Gly646fs sequence mutation have a higher proportion of bone marrow blasts and a worse prognosis. There are no statistical differences in efficacy of different treatment strategies in ASXL1mut group. ASXL1 mutation shows no significant effect on the response of MDS to hypomethylating agent therapy.

The upregulation of CD70 thus suppresses immune cell infiltration into malignant lesions and promotes the exhaustion of CD8 + T cells to facilitate evasion from immunosurveillance. Taken together, our findings define the YAP1-CD70 signaling axis as a novel immunosuppressive mechanism in PCa, which provides new insights into the potential of targeting the CD70 pathway to help further subdivide the population of PCa patients who can benefit from immunotherapy.

Finally, we show that the expression of virally silenced cellular genes remains repressed even after the loss of the virus from infected cells. The results of the current study provide support for how adenovirus could be lost from translocation containing lymphocytes and provide evidence that adenovirus can leave a lasting imprint on cells previously infected in the form of an epigenetic echo.

Patients with RUNX1 mutations had inferior 5 year OS in multivariable analysis (p-value = 0.009). These findings suggest specific genomic alterations that may refine risk stratification and guide future therapeutic protocols in Taiwanese pediatric patients with AML.