B Acute Lymphoblastic Leukemia

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.

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.

P2/3, N=36, Not yet recruiting, Merck Sharp & Dohme LLC

After 75 mg/m2/day mercaptopurine, myelosuppression necessitated a three-week delay prior to the next phase of therapy. With 60 mg/m2/day thioguanine in a subsequent phase of therapy, she was admitted twice for fever and neutropenia...In a larger cohort sequenced for suspicion of rare genetic disease, the frequency of NUDT15*6 was 0.15% among 1011 unrelated individuals. This brief report supports the recent update that patients with the NUDT15*1/*6 genotype should be classified as intermediate metabolizers.

Our findings indicate that although OGM excels at resolving complex structural variants, CMA remains essential for detecting copy-neutral events. Until OGM achieves improved sensitivity for CN-LOH, an integrated approach utilizing conventional cytogenetics, CMA, NGS, and OGM provides the most reliable framework for comprehensive genomic assessment across cancer types.

These findings provide preclinical proof-of-concept that BLINA and ABATA can be combined to uncouple GvL from GvHD. This strategy preserves CD28-independent T-cell cytotoxicity while limiting allo-reactivity, providing a strong rationale for investigating this combination in the post-transplant setting.

P2, N=32, Not yet recruiting, Institute of Hematology & Blood Diseases Hospital, China

Furthermore, LO metabolically reprogram MSC and prime MSC towards differentiation into adipocytes capable of sustaining B-ALL cell growth. Thus, LO-educated MSC, and the adipocytes derived from them, support B-ALL cells by distinct mechanisms, and targeting of LO-mediated communication pathways to prevent B-ALL progression has potential for the development of novel adjuvant treatment strategies.

Furthermore, single-cell transcriptomics suggests that anti-CypA treatment reduces the proportion of cells with multipotent progenitor features and is accompanied by decreased CREB pathway activation. Collectively, these findings indicate that eCypA contributes to the progression of B-ALL and may represent a potential therapeutic target.

These findings suggest that SP dynamics may be linked to the early inflammatory response during CRS and support further investigation of the SP-NK1 receptor axis as a potential therapeutic target to modulate CD19 CAR-T-related toxicity.