T Acute Lymphoblastic Leukemia

Intracellular ATP levels were reduced in Jurkat cells, whereas no significant change was observed in MOLT-4 cells. In parallel, transcriptional analyses revealed downregulation of CD69 and IL-2 and upregulation of RELA proto-oncogene, NF-κB subunit and CBL proto-oncogene B. Collectively, these results demonstrate that TTFields induces cytostatic and apoptotic effects accompanied by measurable structural, bioenergetic and transcriptional alterations in T-ALL cells, supporting further investigation of TTFields as a physical therapeutic approach for hematologic malignancies.

P1, N=18, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting

P1, N=45, Active, not recruiting, Baylor College of Medicine | Recruiting --> Active, not recruiting | N=27 --> 45 | Trial completion date: May 2040 --> Mar 2041

Cypripedin induces apoptosis in Jurkat T-ALL cells, synergizes with BTZ, and modulates ER stress through GRP78 ubiquitination. These findings support its further development as a potential T-ALL therapeutic.

The scFv-NRR module also functioned as a protease-activated pro-antibody that conditionally inhibited DLL4-dependent signaling and ligand-independent activation of mutant NOTCH1 in the T cell acute lymphoblastic leukemia cell line HPB-ALL. Together, these results establish ProNotch as a modular platform for engineering protease-responsive cells and demonstrate that its regulatory module can be extended to a soluble, conditionally activated inhibitor of NOTCH1 signaling.

CD48 expression is diminished compared with normal background T cells in most cases of T-ALL at diagnosis and posttherapy, whereas it was typically retained in mature T-cell/natural killer-cell neoplasms. While CD48 levels may fluctuate after chemotherapy in T-ALL, reduced CD48 can be used as a marker of immaturity in most MRD cases. Potential confounders in the assessment of CD48 include alemtuzumab therapy and the presence of GPI-deficient populations.

IL37 and C17orf99 genes showed downregulated expression, while IL1F10 gene showed upregulated expression in B-ALL. Dysregulated expression of these genes was associated with B-ALL and may be of significance in disease identification. However, further research is warranted to understand these molecular vulnerabilities in B-ALL.

P=N/A, N=60, Recruiting, Washington University School of Medicine | Not yet recruiting --> Recruiting

P2, N=90, Not yet recruiting, SWOG Cancer Research Network

P=N/A, N=148, Completed, The Children's Hospital of Zhejiang University School of Medicine | N=69 --> 148 | Trial completion date: Dec 2022 --> Dec 2025

Interestingly, aCD7P-VCR treatment substantially reduced leukemia progression and invasion in the orthotopic CCRF-CEM T-ALL model without toxic effects, leading to significantly longer survival than clinically used VCR and nontargeted P-VCR. aCD7P-VCR is expected to provide an effective and targeted therapeutic approach for T-ALL.

By developing and characterizing a unique RiboCancer cell line panel, we mapped translational rewiring driven by the most frequent somatic RP mutations. We provide unprecedented mechanistic insights into translation defects induced by CLL-associated Rps15 mutations, and reveal an intriguing translation-based rewiring of transcription in CLL.