Acute Promyelocytic Leukemia

Moreover, upregulation of miR-140-3p expression in APL cells inhibits cell proliferation, arrests cell cycle progression, and promotes apoptosis and cell differentiation. Monitoring the levels of miR-140-3p and HGF may predict the risk of disease recurrence, and interfering with the miR-140-3p / HGF pathway may have therapeutic potential for treating recurrent APL.

These results suggest that SERS analysis of DNA represents a promising method for the MRD monitoring of APL patients. Future validation of these findings in large prospective studies is warranted.

Arsenic trioxide (ATO) is an effective therapeutic agent for acute promyelocytic leukemia; however, its long-term use can lead to cardiotoxicity, particularly in cases of acquired long QT syndrome (acLQTS), which may result in torsade de pointes (TdP)...Tanshinone IIA and fexofenadine restored the hERG protein levels potentially by decreasing MALAT1 expression and counteracting ATO's effects on the MALAT1/calpain-1 pathway. Collectively, our research uncovers a previously unreported regulatory mechanism underlying ATO-induced acLQTS. Moreover, it identifies potential molecular targets and intervention strategies for acLQTS therapy.

High risk stratification, hemorrhage, elevated WBC, LDH, ANC and FDP levels are independent risk factors for coagulation dysfunction in APL patients. The logistic regression model and neural network model based on these risk factors demonstrate good predictive performance for coagulation dysfunction in APL patients.

P3, N=135, Completed, Technische Universität Dresden | Active, not recruiting --> Completed | N=280 --> 135

This study provides a rare instance of a TP53 positive case with APL-like bone marrow morphology, no RARA rearrangement, and MYC amplification. It further lends evidence towards comprehensive cytogenomic and molecular analyses for accurate risk stratification and subsequent disease tracking.

Thus, short-type APL was hierarchically organized by self-renewing APL-LSCs. The identification of LSCs in a subset of APL and establishment of an efficient patient-derived xenograft model may contribute to further understanding the APL leukemogenesis and devise individual treatments for the eradication of APL LSCs.

P2, N=30, Recruiting, Shanghai Jiao Tong University School of Medicine | Trial primary completion date: Jan 2025 --> Jan 2026

Incorporating LEF1into risk stratificationcould help to minimize earlydeaths. Future studies should explore combined risk factor analyses forimproved prognosis in APL patients.

The regulatory mechanisms of HOXA-AS2 include inducing epithelial-mesenchymal transition (EMT), overexpressing B-cell lymphoma-2 (Bcl-2) and MYC proto-oncogene (c-Myc), gene silencing, activating AKT-MMP signaling pathways, EZH2 and LSD1, and functioning within a competing endogenous RNA (ceRNA) regulatory network by competitively binding miRNAs. This review surveys recent research on the structure, biological functions, abnormal expression, regulatory mechanisms, and diagnostic and therapeutic potential of HOXA-AS2 in various cancers.

This study highlights distinct hematopathological patterns of AML with overt DIC, providing a framework for early and precise diagnosis. Recognizing these patterns is critical for tailoring diagnostic and therapeutic approaches to improve outcomes in this high-risk population.

A. Sahebkar disagrees with the retraction, the other co-authors remained unresponsive.

We present an uncommon case of a humeral APL/GS, and conducted a comprehensive analysis of 28 cases of APL/GS. Despite the rarity of APL/GS, it should be diagnosed at an early stage. Furthermore, ATRA are recommended in the treatment plan of APL/GS.

No abstract available

P1/2, N=336, Completed, Constellation Pharmaceuticals | Active, not recruiting --> Completed

A comparison with conventional glass microstructures suggests lower sensitivity but highlights the potential of additive manufacturing for prototyping microfluidics. This may contribute to the wider use of microfluidics in biotechnological or medical applications.

Our study expands the clinical and molecular spectrum of NUP98-r acute leukemias and recommends FISH testing for NUP98 rearrangement on those leukemia cases without recurrent gene rearrangements and/or normal karyotype followed by molecular confirmation to improve timely diagnosis and clinical management.

As expected, the patient achieved complete remission within two months of treatment with ATRA in combination with arsenic trioxide (ATO) and had a favorable prognosis during the three-year follow-up. Our study highlights the accuracy and efficacy of the PML-RARA zebrafish model in combination with protein structure prediction in support of clinical treatment strategies.

The model dynamics was thoroughly analysed using tools integrated in the public software suite maintained by the CoLoMoTo consortium (https://colomoto.github.io/). The model serves as a solid basis to assess the roles of novel regulatory mechanisms, as well as to explore novel therapeutical approaches in silico.

Furthermore, HDAC inhibitors effectively suppress CR-driven leukemia in vitro and in vivo. Hence, our data reveals the molecular bases of oncogenic CR fusion and provides a potential therapeutic approach against AML with CR fusion.

Leveraging Connectivity Map resources and high-throughput screening, we identify venetoclax, homoharringtonine, and daunorubicin as potential therapeutic options for RARG-AML. Overall, our findings provide pivotal insights into the molecular mechanisms governed by RARG fusions and enhanced by WT1 loss in AML development and propose a rational therapeutic strategy for RARG-AML.

Finally, it could achieve both direct detection of serum cell-free RNA and specific intracellular RNA detection. Owing to its isothermal characteristics, robustness, and suitability for point-of-care testing, this method offers a powerful tool for the early diagnosis of APL and the monitoring of MRD, which holds a great significance for facilitating treatment response assessment and making treatment decisions.

Pathway analysis using DAVID software indicated that "viral protein interaction with cytokine and cytokine receptor" and "cytokine-cytokine receptor interaction" were enriched with high significance. Real-time PCR analysis demonstrated that genes for components of these pathways, including chemokines like CCL1, CCL2, CCL3, CCL5, and CXCL8 as well as cytokines and receptors like CSF1, IL-10, IL-10RA, IL-10RB, IL-1β, and TNFSF10, were upregulated in NB4 and HL-60 cells during TCN and PD169316-induced differentiation.

The findings highlight the patients exhibiting the CD34-HLA-DR- immunophenotype as a unique AML subgroup with specific clinical and molecular traits, notably a predisposition to DIC, which affecting prognosis. This finding has implications for risk stratification and potential targeted therapies for AML management.

Our study elucidates the critical role of NEAT1-mediated autophagy in the differentiation of APL cells and delineates the molecular mechanism by which upregulation of NEAT1 enhances autophagy. Specifically, NEAT1 binds to the RNA-binding protein TAF15, which in turn stabilizes the mRNA of both ATG10 and ATG12.

Our findings allow a novel interpretation of the interplay between NOX 2 activation and mitoO2.- formation induced by ATO, ultimately steering leukemic cells towards MPT-dependent apoptosis. These mechanistic insights provide a rationale for the disparate responses of APL and AML cells to ATO, offering potential avenues for the development of therapeutic intervention tailored to specific leukemia subtypes.

Diagnosis relies on clinical, morphological, phenotypic, and cytogenetic evidence, with treatment involving all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Hypogranular acute promyelocytic leukemia (AML3v) is a rare form and is even rarer when it is discovered following an ischaemic event, which is what makes our case so special.

The ICC diagnostic criteria are clinically significant for determining AML prognosis. In line with the changing treatment paradigm for AML, future research is needed to continuously validate diagnostic and risk stratification systems.

All-trans retinoic acid (ATRA) is well known for its effectiveness in acute promyelocytic leukemia (APL) treatment and has already been shown to have synergistic effects combined with another TKI, sorafenib. Finally, in a xenotransplantation model ATRA plus AC220 was more efficient to reduce the leukemic burden than monotherapy with ATRA or AC220. Taken together, our results are a proof of the concept that ATRA and AC220 have synergistic anti-leukemic effects.

Since 2017, a turning point in AML research, 12 agents have received regulatory approval for AML in the United States: venetoclax (BCL2 inhibitor); gemtuzumab ozogamicin (CD33 antibody-drug conjugate); midostaurin, gilteritinib, and quizartinib (fms-like tyrosine kinase 3 inhibitors); ivosidenib, olutasidenib, and enasidenib (isocitrate dehydrogenase 1 and 2 inhibitors); oral azacitidine (a partially absorbable formulation); CPX351 (liposomal encapsulation of cytarabine:daunorubicin at a molar ratio of 5:1); glasdegib (hedgehog inhibitor); and recently revumenib (menin inhibitor; approved November 2024). Oral decitabine-cedazuridine, which is approved as a bioequivalent alternative to parenteral hypomethylating agents in myelodysplastic syndrome, can be used for the same purpose in AML. Menin inhibitors, CD123 antibody-drug conjugates, and other antibodies targeting CD123, CD33, and other surface markers are showing promising results. Herein, the authors review the frontline and later line therapies in AML and discuss important research directions.

Notably, gene silencing experiments confirmed the critical roles of both NRF2 and AHR in mediating ATOIII-induced NQO1 expression. In conclusion, ATOIII exposure is found to upregulate the NQO1 enzyme through a transcriptional mechanism via AHR- and NRF2- dependent mechanisms, offering valuable insights into its therapeutic mechanisms.

This is the first case report of AML with NUP98::RARG rearrangement in Japan. Qualitative RT-PCR analysis for NUP98::RARG mRNA was helpful for the accurate diagnosis and evaluation of MRD to choose an adequate treatment for this type of AML.

This simple, cost-effective tool, with its easy-to-read format, is particularly valuable in under-resourced regions. The assay facilitates timely diagnosis and prompt administration of lifesaving therapies such as all-trans retinoic acid and arsenic trioxide in APL.

The present research depicted that BIS and TMZ have the potential to protect the heart and provide therapeutic benefits by preventing acute heart injury induced by ATO. This is achieved by reversing the redox-sensitive pathway, reducing inflammation, and inhibiting apoptosis.

This study demonstrates the therapeutic potential of venetoclax in combination with ATO in vitro and strongly encourages further investigation of relapsed/refractory APL with high BCL2 expression.

This is the first report of an insertional PML::RARA fusion into the RARA gene on 17q detected by OGM. OGM has demonstrated its utility in a clinical cytogenetics environment, allowing for clearer characterization and diagnosis of various neoplasms.

This study also revealed FLAER differences in other acute leukemias and even between different precursors (myeloid and lymphoid) from healthy controls. However, the reason for FLAER's non-binding to the malignant precursors of these leukemias remains unknown, and future studies should explore the possible relation with an immune escape phenomenon in these leukemias.

By replacing the hPGK promoter with the elongation factor-1 alpha (EF1α) promoter, we successfully achieved high transduction efficiency and robust selection, demonstrating the potential for this modified vector system to facilitate genetic studies in APL models. These findings provide important insights into optimizing gene transduction protocols not only for NB-4 cells but also for other challenging cell lines, offering a refined approach for gene delivery and selection in cell models.

P1, N=55, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Sep 2024 --> Sep 2025 | Trial primary completion date: Sep 2024 --> Sep 2025

P=N/A, N=15, Not yet recruiting, Zhejiang Provincial People's Hospital; Zhejiang Provincial People's Hospital

P=N/A, N=56, Not yet recruiting, The First Affiliated Hospital,Sun Yat-sen University; The First Affiliated Hospital,Sun Yat-sen University

P3, N=158, Active, not recruiting, Children's Oncology Group | Trial completion date: Sep 2024 --> Sep 2025