Hematological Malignancies

This case report presents two cases of B-lymphoid/myeloid MPAL with MLL-AF4 genetic abnormality successfully treated with a chemo-free regimen composed of venetoclax, hypomethylating agents, and blinatumomab and achieved complete remission (CR). Considering the results of this case report, the combination of a chemotherapy-free regimen could be considered a safe and effective treatment approach for patients with B-lymphoid/myeloid MPAL.

P1/2, N=160, Recruiting, Sellas Life Sciences Group | Trial primary completion date: Jun 2025 --> Dec 2025

P1, N=140, Active, not recruiting, Janssen Research & Development, LLC | Trial primary completion date: Jun 2025 --> Apr 2027

P2, N=7, Terminated, Icahn School of Medicine at Mount Sinai | Active, not recruiting --> Terminated | Trial primary completion date: Jan 2025 --> Jun 2025; No significant improvement in disease as graded by our assessments.

P2, N=65, Not yet recruiting, Masonic Cancer Center, University of Minnesota | Initiation date: Jul 2025 --> Oct 2025

P2, N=31, Not yet recruiting, Medical College of Wisconsin | Initiation date: Jun 2025 --> Oct 2025

P1, N=24, Not yet recruiting, Stanford University | Initiation date: Jun 2025 --> Sep 2025

P=N/A, N=150, Recruiting, Fondazione Italiana Linfomi - ETS | Trial completion date: Jul 2025 --> Dec 2025 | Trial primary completion date: May 2025 --> Dec 2025

P3, N=720, Recruiting, Merck Sharp & Dohme LLC | Trial completion date: Jun 2033 --> Mar 2035 | Trial primary completion date: Jun 2033 --> Mar 2035

P=N/A, N=2300, Recruiting, Xuanwu Hospital, Beijing | Trial completion date: Dec 2026 --> Oct 2028

P2, N=72, Recruiting, Mayo Clinic | Trial completion date: Aug 2027 --> Aug 2029

P=N/A, N=880, Recruiting, Murdoch Childrens Research Institute | Trial completion date: Aug 2026 --> Aug 2027 | Trial primary completion date: Aug 2025 --> Aug 2026

P=N/A, N=200, Active, not recruiting, OHSU Knight Cancer Institute | Trial completion date: Apr 2025 --> Dec 2025

P4, N=295, Recruiting, Janssen Research & Development, LLC | Trial completion date: Jul 2037 --> Oct 2037

P2, N=28, Recruiting, Fondazione Italiana Linfomi - ETS | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Jan 2025 --> Jan 2026

P1, N=60, Recruiting, St. Jude Children's Research Hospital | Trial completion date: Jun 2027 --> Jul 2028 | Trial primary completion date: Jun 2026 --> Jul 2027

P=N/A, N=39, Completed, Second Affiliated Hospital, School of Medicine, Zhejiang University | Trial completion date: Oct 2020 --> Oct 2024

P=N/A, N=110, Recruiting, Medical College of Wisconsin | Trial completion date: May 2025 --> May 2026 | Trial primary completion date: May 2025 --> May 2026

P1, N=29, Active, not recruiting, Roswell Park Cancer Institute | Trial completion date: Jun 2025 --> Dec 2025

P2, N=108, Active, not recruiting, City of Hope Medical Center | Trial completion date: Jun 2025 --> May 2026 | Trial primary completion date: Jun 2025 --> May 2026

P1, N=136, Recruiting, Baylor College of Medicine | Trial completion date: Jul 2026 --> Jul 2027 | Trial primary completion date: Mar 2026 --> Mar 2027

Furthermore, CD4+ T cells from patients with ATL expressed less BLIMP1 and had enhanced IL-2 signaling, whereas overexpressing PRDM1 in ATL cells suppressed IL-2 signaling. Thus, BLIMP1 inhibits IL-2 signaling during normal and pathophysiological responses, suggesting that manipulating BLIMP1 could have therapeutic potential.

P1/2, N=19, Terminated, NuCana plc | N=91 --> 19 | Trial completion date: Dec 2025 --> May 2025 | Recruiting --> Terminated | Trial primary completion date: Dec 2025 --> May 2025; The NuTide:303 study was terminated at NuCana's discretion due to refinement of the pipeline strategy. The overall risk benefit assessment of NUC-3373 remains positive and future NUC-3373 studies are under consideration.

P1, N=18, Recruiting, AstraZeneca

P1/2, N=30, Recruiting, Zhujiang Hospital

P2/3, N=1708, Not yet recruiting, Children's Oncology Group

In summary, fourteen hub genes were identified as potential regulators in the osteo-adipogenic differentiation of MSCs. Among them, ARNT2 was confirmed to promote osteogenesis in MSCs and exhibited potential as a therapeutic target for bone-related diseases.

The EAP regimen demonstrated significantly enhanced mobilization efficiency compared to the G-CSF monotherapy while maintaining an acceptable toxicity profile. These findings suggest that the EAP regimen may represent a superior alternative for mobilizing hematopoietic stem cells in patients with multiple myeloma or lymphoma.

A 53-year-old woman was diagnosed with MDA5 dermatomyositis and treated for rapidly progressive interstitial lung disease using multidrug immunosuppressive therapy with prednisolone (PSL), tacrolimus, and intravenous cyclophosphamide pulse therapy...Chemotherapy, including high-dose methotrexate (MTX) and rituximab, prevented tumour recurrence without exacerbating interstitial lung disease...Chemotherapy, including high-dose MTX and rituximab, can be used for central OIIA-LPD without aggravating settled interstitial lung disease. The activity of MDA5 dermatomyositis during OIIA-LPD treatment may be managed with low-dose PSL.

This case expands the known spectrum of cutaneous and systemic manifestations in anti-NXP2 antibody-positive DM and emphasizes the heterogeneous nature of DM, where significant clinical mimicry can occur despite the presence of a well-defined MSA. It highlights the need for further research into the immune mechanisms and biomarker profiles driving these mimicking DM phenotypes, which could improve early diagnosis, risk stratification, and targeted therapeutic strategies.

HMAs and venetoclax could benefit newly diagnosed younger patients with ASXL1-mutated AML.

In this study, we extended these in vitro findings to demonstrate similar sensitivity to the second-generation STAMP inhibitor, TERN-701, using ZC3HAV1::ABL2 ALL cells. Importantly, this suggests that, in the clinical setting, different asciminib binding site mutations may be anticipated with STAMP treatment for ABL2r ALL. Finally, we demonstrated the efficacy of both STAMP inhibitors against cells from patients with ZC3HAV1::ABL2 and asciminib as a novel treatment for ZC3HAV1::ABL2 disease in a preclinical in vivo study.

AI was confirmed (serum cortisol level, 1.5 μg/dL; adrenocorticotropic hormone level, 82 pg/mL), prompting hydrocortisone replacement...BL, although rarely involving the adrenal glands, should be considered in unexplained AH. This report highlights the importance of considering malignancy in unexplained AH and AI, even without conventional risk factors.

Notably, TRIM44 conferred chemoresistance to doxorubicin in DB cells by increasing autophagic activity...The results of miRNA pull-down and luciferase reporter assay indicated that TRIM44 was a direct target of miR-665. In conclusion, TRIM44 promoted DLBCL progression by increasing autophagy-mediated chemoresistance, revealing the involvement of miR-665/TRIM44 axis.

Vectors targeted to either CD3 or CD8 similarly generated high levels of CAR T cells which rapidly eradicated B cells suggesting that TCR engagement is not required for lentiviral vectors to efficiently transduce T cells in vivo. Furthermore, the 4th generation lentiviral vector platform (referred to as TetraVecta™ system) employs the TRiP system™ to prevent incorporation of CAR protein into the vector particles, minimizing the risk of inadvertent transduction of tumour cells.

The prognostic value of GNG4 was further validated in AML patient samples through qRT-PCR.ConclusionClinical validation indicated a substantial downregulation of GNG4 in AMLNPM1mutFLT3-ITDmutDNMT3Amut compared to AMLNPM1mutFLT3-ITDmutDNMT3Awt patients. Thus, GNG4 may play a role in the low survival rate of AMLNPM1mutFLT3-ITDmutDNMT3Amut patients, offering novel insights into the prognosis, therapeutic targets, and prognostic evaluation of AML.

Additionally, the AI-based virtual ICC has demonstrated capabilities in cell counting, cell spatial distribution, cell segmentation, and classification. It offers a rapid, accurate, and precise evaluation of FNA samples and has the potential to help advance diagnostic cellular and molecular pathology capabilities.

This review also includes gene editing to target oncogenic drivers or correcting mutations and USP inhibition to overcome resistance. Finally, it concludes by emphasizing the importance of combining these diverse therapeutic approaches with ongoing next-generation TKIs and comprehensive and personalized approaches for CML treatment, offering a path toward deeper remissions and ultimately achieving curative outcomes for CML patients.

These findings establish a mechanistic rationale for the concurrent targeting of the MDM2 and STAT3 axes and provide preclinical evidence for a promising, non-genotoxic therapeutic strategy in p53-functional CLL. A limitation of this study is the lack of in vivo validation and clinical data, which are necessary to further assess the safety, optimal dosing, and efficacy, particularly in elderly or unfit patients with limited treatment options.

The model constructed based on the random forest algorithm demonstrates potential in screening IgD MM patients, particularly when routine IgD immunotyping testing is not conducted in clinical practice. This can assist clinicians in early diagnosis and personalized treatment strategies, thereby optimizing the utilization of medical resources.

Additionally, combining CAR-T therapy with surgery may reduce tumor recurrence and positively influence reconstructive outcomes. Overall, this review underscores CAR-T cell therapy as a potential adjunctive treatment in oncologic surgery, emphasizing the importance of interdisciplinary approaches to improve patient outcomes in solid tumor management.

P1/2, N=12, Completed, SDK Therapeutics, Inc. | Recruiting --> Completed