Acute Promyelocytic Leukemia

Insertion sites located in Hinge Region(HR)/β1 domain and juxtamembrane domain (JMD) derived significantly greater benefit from early FLT3 inhibitor therapy(primarily sorafenib), showing significantly prolonged overall survival...In the era of FLT3-ITD targeted drug therapy combined with transplantation, the insertion site of FLT3-ITD based on high throughput sequencing results helps predict the efficacy of FLT3 inhibitors. Integrating white blood cell count with HR/β1 insertion site can identify a high-risk patient subgroup likely to benefit from FLT3 inhibitor therapy.

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.

Fenofibrate effectively counteracted these effects by activating PPARα, thereby competitively inhibiting RARα binding to RXRα and restoring lipid homeostasis. This study reveals a novel mechanism underlying ATRA-induced hyperlipidemia and hepatic lipid accumulation, which offers a theoretical foundation for the clinical use of fenofibrate in managing ATRA-induced hyperlipidemia and hepatic steatosis.

We demonstrate that the E3 ligase UBE2O catalyzes dual-site monoubiquitination of NLRP6: at K680-687 to drive oligomerization via a conformational change, and at K115/130 within the nuclear localization signal to enforce cytoplasmic sequestration through steric hindrance. Furthermore, the UBE2O inhibitor arsenic trioxide suppresses NLRP6-dependent interleukin (IL)-18 secretion in acute promyelocytic leukemia (APL) patients. Thus, UBE2O-mediated dual-site monoubiquitination emerges as a central mechanism licensing NLRP6 inflammasome activation, revealing a new target for modulating intestinal immunity.

Furthermore, the article explores the importance of the immune system in acute promyelocytic leukemia treatment response and the impact of all-trans retinoic acid/arsenic trioxide therapy on the proteome and metabolome. By synthesizing existing research findings, this review aims to discuss how proteomic and metabolomic data elucidate the pathological mechanisms and therapeutic targets of acute promyelocytic leukemia, providing a theoretical basis for future precision medicine and translational research.

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.

P3, N=120, Not yet recruiting, SDK Therapeutics, Inc.

Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia characterized by the promyelocytic leukemia-retinoic acid receptor alpha (PML-RARA) fusion gene and exceptional responsiveness to differentiation therapy with all-trans retinoic acid (ATRA) and arsenic trioxide (Arsenic Trioxide)...Anthracycline-based chemotherapy was subsequently administered, followed by azacitidine combined with venetoclax in the subsequent course of treatment...A literature review suggests that FIP1L1-RARA-positive APL represents a biologically and clinically distinct entity with highly variable treatment responses and poor prognosis. Early molecular diagnosis and prompt implementation of conventional chemotherapy or targeted therapies such as venetoclax may be essential to improving outcomes in this rare APL subtype.

Using the median soluble podoplanin value as a cutoff, a higher proportion of APL patients presented elevated levels. Soluble podoplanin levels correlated with CD40L in APL cases, but not in non-APL AML patients, suggesting a possible interaction with thrombo-inflammatory activation pathways These findings represent a proof-of-concept that measuring soluble podoplanin in plasma samples can contribute to the diagnosis of APL, while also providing novel data on the association of podoplanin with the pathogenesis of APL coagulopathy.

P2, N=151, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2027

All patients received induction therapy with all-trans retinoic acid, arsenic trioxide, or both...Elevated peak WBC, hypoalbuminemia, and lack of prophylactic corticosteroids are independent predictors of DS in APL patients. These findings underscore the importance of early risk stratification and preventive strategies to mitigate DS risk during induction therapy.

For relapsed and refractory APL, relevant drug resistance gene monitoring should be carried out. Some relapsed and refractory APL patients who do not respond to conventional treatment are at risk of death. We report a successful case, the regimen of VEN targeted therapy combined with chemotherapy still holds promise for the treatment of future relapsed/refractory APL.