PML (Promyelocytic Leukemia)

P3, N=158, Active, not recruiting, Children's Oncology Group | Trial completion date: Sep 2025 --> Jun 2029

Early diagnosis of acute promyelocytic leukemia (APL), driven by PML-RARA oncoprotein, is vital for survival, as delays can cause fatal coagulopathy without prompt therapeutic intervention of all-trans retinoic acid and arsenic trioxide...Pharmacological inhibition of TGF-β1 ligand using luspatercept reduced SMAD phosphorylation and PDPN expression, indicating TGF-β/SMAD transcriptionally regulates PDPN. Additionally, ELISA-based serum profiling showed significantly elevated TGF-β1 levels in APL patients compared to non-APL AML (p < 0.0001). These findings identify PDPN overexpression as a downstream consequence of TGF-β/SMAD signaling and highlight its potential as a diagnostic biomarker for APL.

Conversely, the N-to-C synthesis method proceeded efficiently without cysteine protection, thereby simplifying the workflow and reducing the number of purification steps. This research presents a reliable and accessible method for the complete chemical synthesis of RNF4, addressing significant challenges in synthesizing large proteins and opening up new opportunities for future biological research.

The absolute mortality risk reduction was 16%, yielding a number-needed-to-treat of seven. Early ED ATRA initiation substantially improved survival in PML-RARA-confirmed APL.

Compared with non-APL-AML patients, APL patients (PML-RARα (S-type) and PML-RARα (L-type)) exhibit unique immunophenotypic changes. The expression frequencies of CD56, CD2, CD34, and CD200 in leukemia cells are significantly correlated with the OS of APL patients, and the high expression of these indicators before treatment may be an adverse prognostic factor for APL patients.

Ras promotes cellular transformation by decreasing the expression of SncmtRNA-2 and hsa-miR-620, which may contribute to increased PML expression, suggesting but not demonstrating a possible regulatory relationship among these molecules in HPV-immortalised cells. These results highlight a potential SncmtRNA-2/miR-620/PML axis that requires further validation through direct interaction assays and functional necessity/sufficiency experiments.

Notably, demethylation therapy induced sustained complete remission in patients with refractory recurrent APL during experimental treatment. Our findings underscore the critical role of ALDH1A3 in leukemogenesis and highlight its potential as a therapeutic target in APL.

This work provides a robust tool for early APL diagnosis. The proposed triple-amplification strategy and the rational design of the ECL-RET platform offer a generalizable and versatile sensing paradigm, which can be readily adapted for the ultrasensitive detection of a wide range of other disease-related nucleic acid biomarkers and infectious pathogens.

P1, N=48, Active, not recruiting, National Cancer Institute (NCI) | Suspended --> Active, not recruiting

Despite the high efficacy of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) in treating acute promyelocytic leukemia (APL), approximately 10-20% of patients develop drug resistance due to mutations in PML-RARα and other factors...Consistent with PML-RARα degradation, ML364 treatment significantly induces apoptosis in APL cell lines and primary leukemia cells. In conclusion, this study identifies USP2 as a novel deubiquitinating enzyme for PML-RARα and highlights USP2 inhibition as a potential therapeutic strategy for APL with PML-RARα mutations.

P2, N=153, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2027