Acute Lymphocytic Leukemia

Group A showed no significant difference in the total efficacy rate and 5-year overall survival after treatment (p > 0.05) and had lower medical expenses, length of hospital stay, IL-6 and TNF-α expression, and total incidence of adverse reactions and higher KPS scores than group B (p < 0.05). Although no significant difference was observed between vindesine and leurocristine in treating pediatric acute lymphoblastic leukemia, patients administered vindesine had fewer adverse reactions, shorter length of hospital stay, lower medical expenses, and higher quality of life than those administered leurocristine, indicating a potential association with decreased serum IL-6 and TNF-α expression.

Collectively, our findings define CEBP and ZEB2 alterations as drivers of genetically and clinically distinct subtypes of adult B-ALL and provide a rationale for subtype-specific risk stratification. Preclinical experiments in CEBPalt B-ALL patient-derived xenografts demonstrated sensitivity to FLT3 inhibition, highlighting a potential therapeutic vulnerability.

Overexpression of anti-apoptotic protein BCL-2 and hypermethylation are hallmarks of acute lymphoblastic leukemia (ALL) and can be pharmacologically addressed by venetoclax (VEN) and hypomethylating agents (HMA) such as azacytidine (AZA) or decitabine (DEC). AZA-induced metabolic suppression as well as overall anti-leukemic activity alone and in combination with VEN was generally weaker compared to DEC. Altogether, we herein demonstrate that combined VEN and HMA application acts synergistically and significantly reduces the leukemic burden in ALL cell lines via impairment of tumor cell metabolism and mitochondrial function.

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=20, Recruiting, The First Affiliated Hospital of Soochow University | Active, not recruiting --> Recruiting | Trial primary completion date: Jul 2026 --> Nov 2025

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

P1, N=12, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: May 2026 --> May 2027 | Trial primary completion date: May 2026 --> May 2027

P=N/A, N=85, Completed, University Hospital, Angers | Unknown status --> Completed | N=150 --> 85 | Trial completion date: Jan 2022 --> Jul 2025 | Trial primary completion date: Jan 2022 --> Jul 2025

Our in vitro findings indicate that TP53 deficiency in B-ALL cells downregulates adhesion networks and impairs immunogenic signaling, which correlates with accelerated CAR-T cell exhaustion. These transcriptomic and cellular observations suggest a potential link between TP53-mediated adhesion loss and CAR-T resistance, warranting further in vivo validation and biophysical investigations.

These patterns are consistent with signaling processes linked to immunoregulation, leukemic supportive signaling, and therapeutic resistance in B-ALL. Together, these findings indicate that the bone-marrow-on-a-chip captures relevant aspects of niche-associated signaling and provides a versatile platform for investigating leukemia microenvironment interactions, with potential in drug screening and preclinical model development.

Inotuzumab ozogamicin showed high activity as reinduction treatment in paediatric very high risk first B-cell acute lymphoblastic leukaemia relapse and a favourable toxicity profile with no treatment-related deaths.