Hematological Malignancies

Whereas ND-L11B induced selective multiple myeloma cytotoxicity, it could serve as a starting point for the further development of NSD2-targeting therapies. This work provided a convenient chemical knockdown tool to further elucidate the multiple functions of NSD2 isoforms and expanded the applicability of alkyl primary amine analogs for targeted protein degradation.

With the acceptable oral bioavailability of 19.2 % in SD rats, 12y prolonged the survival rate of NSG mice dose-dependently in MOLM-13 inoculated xenograft model without obvious toxicity. Overall, this study might provide a new insight for the development of novel FLT3 inhibitors.

In this real-world study, early discontinuation was more common in patients initiating a BTKi in contrast to VEN-O. Patients who initiated a BTKi also had high rates of subsequent treatment and hospitalization.

Voruciclib treatment led to a decrease in MCL1 mRNA expression, downregulation of MYC and NF-κB transcriptional gene sets, and reduced phosphorylation of RNA polymerase II. Voruciclib on intermittent dosing was well tolerated, with no DLTs, paving the way for evaluation of the combination of voruciclib with venetoclax in patients with previously treated AML.

No abstract available

This case was facilitated by the early detection of discrepancies between lipemia indices and sample appearance despite normal examination results. Additionally, close collaboration between clinical laboratory technicians and clinicians facilitated the uncovering of subtle early disease changes, thereby aiding in precise diagnoses.

Among these, 11 were found to exert a protective effect against MPN, 5 phenotypes were associated with an elevated risk of MPN. This research highlights a significant association between various immune cell phenotypes and the risk of developing MPN, thereby advancing our understanding of the intricate interplay between immune cell traits and the progression of MPN.

Our study revealed that the downregulation of DNMT expression may be a new target for the treatment of AML.

Since JAK/STAT signaling contributes to AML survival, our findings suggest that the downregulation of JAK/STAT genes by BM-MSC exosomes in leukemic cells may aid in designing a potent therapeutic strategy for AML treatment.

Detected mutations were not found to be relevant to pathogenesis of T-LBL and MPN in previous reports and were considered variants of uncertain significance. Based on the WES results, ETV6::LYN fusion gene was considered the driver gene essential for the pathogenesis of MPN-TK with ETV6::LYN.

The mRNA level of the Bax elevated to 1.98 folds, and the Bcl-2 gene was downregulated to 0.33 folds, underscoring the mechanism by which ZnO-Rutin NPs promote apoptosis. This study highlights the efficient anticancer potential of ZnO-Rutin NPs against CML cells, providing the basis for further investigations into their clinical applicability and underlying mechanisms of action.

The non-stochastic distribution of the IGKV/LV gene expression in the individual stereotyped subsets was confirmed. Taking into account the complementary role of the light chains in antigen recognition by the clonotypic BCRs, it was suggested that the subsets with the heterogeneous IGK/LV expression might be reclassified and divided into separate subgroups based on the IGHV and IGK/LV association.

Our results suggest that IKZF1 rs4132601 and IKZF3 rs907091 may affect response to treatment and progression in patients with MM.

Partial positivity for CD23 is a common feature of LPL in the BM. Together with other clinical and histological parameters, CD23 expression supports the differential diagnosis between LPL and MZL.

Our investigation uncovers that nanomolar concentrations of salinomycin, monensin, nigericin, and narasin (a group of potassium/sodium cation carriers) robustly enhance surface expression of CD20 antigen in B-cell-derived tumor cells, including primary malignant cells of chronic lymphocytic leukemia and diffuse large B-cell lymphoma...The results of RNA-seq, genetic editing, and chemical inhibition delineate the molecular mechanism of CD20 upregulation, at least partially, to the downregulation of MYC, the transcriptional repressor of the MS4A1 gene encoding CD20. Our findings propose the cation carriers as compounds targeting MYC oncogene, which can be combined with anti-CD20 antibodies or adoptive cellular therapies to treat NHL and mitigate resistance, which frequently depends on the CD20 antigen loss, offering new solutions to improve patient outcomes.

At day+1, higher plasma levels of lipid metabolism products and lower glucose and glycoproteins levels were observed in tisa-cel compared to axi-cel-treated patients. Our data show complex metabolomic changes that track the evolution of the disease and drug activity in the first 30 days of CAR-T cell therapy. Conceivably, a pro-inflammatory drift may be linked to a forthcoming disease relapse in CAR-T patients.

The findings of this investigation offer suggestive evidence for possible genetic correlations and causal links between various genetically predicted inflammatory proteins and HS. There exists a pressing requirement for additional studies to elucidate the fundamental processes driving these associations.

Functionally, this results in enhanced sensitivity of leukemic blasts to T cell-mediated cytotoxicity in allogeneic and autologous settings. Our data indicate that JNJ-75276617 provides a potential therapeutic approach whereby not only proliferation is impaired and differentiation is induced, but whereby therapeutic benefit might also be achieved by reactivating the antigen presentation machinery.

He was diagnosed with Rai Stage I CLL with del6q, without TP53 mutation, and treated with 6 cycles of fludarabine, cyclophosphamide, and rituximab (FCR) 6 years prior...The patient received three courses of dexamethasone and acyclovir, leading to successful clearance of the infection, evidenced by the resolution of his B symptoms. Subsequently, he was treated for the CLL recurrence with rituximab and venetoclax, demonstrating a favorable response with significant improvement in adenopathy and resolution of lymphocytosis...Timely administration of antiviral therapy is crucial for HSV lymphadenitis to prevent rapid progression and debilitating symptoms. This case demonstrates the importance of considering atypical viral infection presentations in CLL patients and emphasizes the necessity of timely and adequate biopsies to differentiate between CLL transformation, HSV lymphadenopathy, and other causes of lymphadenopathy while avoiding unnecessarily aggressive lymphoma therapy.

Further, we also established that ARMH1 is a key physical interactant of EZH2, associated with multiple cancers. Our findings underscore further evaluation of ARMH1 as a potential candidate for targeted therapies and stratification of aggressive pAML to improve outcomes.

The exercise training program used in this study was feasible in people with treatment-naïve CLL who passed pre-trial screening, and we preliminarily conclude that the exercise training program was safe and also resulted in an increase in lean mass. https://doi.org/10.1186/ISRCTN55166064, identifier ISRCTN 55166064.

She was successfully treated with intravitreal foscarnet injections and systemic ganciclovir. After 5 months of systemic valganciclovir maintenance and following cessation of chemotherapy, the patient developed bilateral CME and vasculitis, and was diagnosed with IRU...Subsequently, the CME and retinal vasculitis resolved significantly without any evidence of inflammation in the anterior chamber and vitreous. The index case report demonstrated the safety and efficacy of the IL-6 receptor antagonist TCZ in treating CME associated with IRU in a non-HIV CMV retinitis patient.

MiR-625 can be a promising approach to aid in the treatment of AML. However, further studies are required in this field.

60.52% of the patients had an elevated Erythrocyte Sedimentation Rate (ESR), and 73.68% had an elevated C-reactive protein (CRP) level. Despite the outcomes of COVID-19 in most children with cancer in this study, children with cancer still experience risks from COVID-19, and it is unclear how delays and interruptions in cancer treatment and direct damage from the virus may impact long-term outcomes in these patients.

Initially, he was prescribed cyclosporine at a dose of 2.5 mg/kg suspecting a worsening of his psoriasis; however, this treatment was ineffective...After initiating osimertinib at a dose of 80 mg, the skin rash improved, and the tumor size was reduced. The final diagnosis was paraneoplastic erythema annulare centrifugum associated with lung cancer. This case highlights the potential resolution of erythema annulare centrifugum through lung cancer therapy, emphasizing the importance of considering lung cancer differential diagnosis when this skin condition is present.

Genetic inhibition or use of the ADAR1 inhibitor ZYS-1 significantly suppressed AML cell growth both in vitro and in vivo. Overall, these results elucidated the tumorigenic mechanism of ADAR1 and validated it as a potential drug target in AML.

The identified miRNA-gene interactions offer valuable insights for developing targeted therapies for CLL. In addition, we underscored the importance of a practical and robust computational pipeline to ensure the reliability and reproducibility of miRNA sequencing data analysis.

This work brings new insights into the complexity of MYC-dependencies and unravels a novel targetable oncogenic pathway in aggressive B-cell lymphomas.

The present study delineates the genomic distribution of Kaiso in cancer cells, confirming its role as a factor with a complex mode of DNA binding and a strong association with CpG islands, particularly with methylated and eroded CpG islands, revealing a new potential Kaiso target gene-SQSTM1, involved in differentiation of acute myeloid leukemia cells. Furthermore, we discovered the existence of a new class of CpG islands characterized by wave-like DNA methylation.

P1/2, N=130, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2025 --> Jul 2029 | Trial primary completion date: Mar 2025 --> Jul 2024

P2, N=20, Recruiting, Fudan University

P1/2, N=38, Terminated, Hoffmann-La Roche | Completed --> Terminated; Study was terminated by the sponsor based on insufficient tolerability and efficacy to proceed beyond Part 1b.

P=N/A, N=20, Not yet recruiting, Institute of Hematology & Blood Diseases Hospital, China

P1, N=80, Recruiting, Janssen Research & Development, LLC | Not yet recruiting --> Recruiting | Trial completion date: Nov 2027 --> Nov 2028

P2, N=60, Not yet recruiting, Institute of Hematology & Blood Diseases Hospital, China

P1, N=70, Not yet recruiting, Nanjing IASO Biotechnology Co., Ltd.

P=N/A, N=76, Recruiting, National University Hospital, Singapore

P=N/A, N=633, Active, not recruiting, Fondazione Italiana Linfomi - ETS | Trial completion date: Jun 2024 --> Feb 2025

P=N/A, N=300, Recruiting, Janssen Pharmaceutica N.V., Belgium | N=100 --> 300 | Trial completion date: Dec 2027 --> Apr 2028

P=N/A, N=108, Not yet recruiting, Centre Henri Becquerel

P1/2, N=312, Active, not recruiting, Celgene | Trial completion date: Dec 2026 --> Jan 2025

P1, N=18, Active, not recruiting, Uma Borate | Recruiting --> Active, not recruiting | Trial completion date: Jan 2025 --> Dec 2025 | Trial primary completion date: Jan 2025 --> Jun 2025