TP53 (Tumor protein P53)

P2, N=42, Completed, Jennifer Woyach | Active, not recruiting --> Completed | Trial completion date: Dec 2026 --> Jan 2026

P1, N=32, Not yet recruiting, Northside Hospital, Inc.

We illustrate four use cases of ASHOP: (1) stratification of DUX4-rearranged B-cell leukemias into Early/Multipotent and Committed subgroups with distinct outcomes, (2) characterization of HOXA/HOXB expression patterns in acute myeloid leukemias, (3) correlating mutational burden with mismatch repair deficiency and mutational signatures, (4) investigation of TP53 alteration landscape. ASHOP is an open-access resource to inform genomic and transcriptomic data interpretation for hematologic malignancies, and will expand to support additional diseases and data modalities from the ASH community.

Additionally, analysis of 128 patients with a 56-gene panel (18% with rapid growth) identified TP53 as an independent risk factor for fast growth. This study found risk factors associated with fast-growing lung cancers, helping to identify patients at high risk of disease progression.

These findings establish a mechanistic link between hormonal signaling, p53 allelic status, and m6A-dependent post-transcriptional regulation. Although further in vivo validation is required, disruption of the ALKBH5-REG1A axis may contribute to heterogeneous endometrial responses to tamoxifen, thereby providing a conceptual framework for biomarker-oriented investigation.

Furthermore, clonal evolution analysis revealed that the two tumor components shared a set of 160 identical somatic mutations (accounting for approximately 16% of the total mutations in each component). This study delineates a dynamic evolutionary process within the pulmonary neuroendocrine tumor spectrum, confirming that a subset of atypical carcinoids can progress to small cell lung carcinoma through a transformation pathway.

NFκB acts downstream of the T-cell-mediated CD40L:CD40 stimulus, and indeed, CK1δ/ε inhibition efficiently blocked the proliferation of primary CLL triggered by CD40L across multiple patient groups, with lower efficacy in patients with TP53 defects. We propose that CK1δ/ε inhibitors act in the multiple-hit mode, striking both intrinsically via direct interference with cell cycle machinery and extrinsically via inhibition of multiple pro-proliferative stimuli.

Additionally, we explore the mechanisms underlying TP53 mutations in the leukemic transformation of MPNs, including clonal evolution to multihit status and the role of inflammation and therapy. Finally, recent findings on the clinical impact of multihit TP53 mutations and potential strategies for targeting the p53 pathway in MPNs and sAML are presented.

This review synthesizes current knowledge on the unique tumor biology of breast cancer in young women, highlighting the need for precision oncology approaches that account for age-related tumor behavior. Enhanced characterization of this population may ultimately improve survival outcomes and quality of life for young women affected by breast cancer.

Malignant EAML can invade atypical venous routes such as the lumbar vein. Comprehensive imaging, multidisciplinary evaluation, and long-term follow-up are crucial for successful management.

Our study highlights the complementary diagnostic value of p53 and Smad4 IHC relative to molecular testing in PDAC, especially when tissue is limited, as commonly encountered in FNB specimens. The newly established Smad4 IHC classification system, which integrates an intermediate expression category into the conventional two-tier framework, demonstrates superior clinical utility and enhances predictive accuracy for SMAD4 genomic alterations.

The mutational patterns affecting homologous recombination repair differ across gynecologic and breast cancers. Further research into cancer-specific HRD mechanisms is warranted.