Childhood B Acute Lymphoblastic Leukemia

These results identify PD-1 as a new therapeutic target against leukemic progression, providing new opportunities for the treatment and possibly also the prevention of childhood B-ALL.

The data from the CTRP database and the Cell Counting Kit-8 (CCK-8) experiment suggested that SIRT1 increased the sensitivity of B-ALL cell lines to vincristine. In vitro experiments demonstrated that SIRT1 inhibits invasion activity in B-ALL cell lines (NALM6 and REH). SIRT1 represents a potential prognostic biomarker and therapeutic target in childhood B-ALL.

Moreover, NEAT1-fitted multivariate models resulted in improved risk stratification compared to the conventional disease markers of white blood cells, bone marrow response and minimal residual disease, while decision curve analysis highlighted the superior clinical net benefit for chB-ALL prognosis. In conclusion, NEAT1 overexpression constitutes a powerful, independent predictor of poor treatment outcomes and disease progression of chB-ALL, providing refined stratification of patient's risk.

VISTA overexpression and FOXD3 downregulation in B-ALL, alongside altered CD48, and PVRL2 expression, highlight mechanisms of immune evasion. These findings position VISTA as a promising biomarker and target for B-ALL immunotherapy.

These transcripts could serve as biomarkers for two distinct molecular subgroups of B-ALL, each with different risk profiles at diagnosis. This is the first study characterizing the long transcriptome in blood-derived sEVs for childhood B-ALL, highlighting the potential use of circulating RNAs for improved risk-based stratification.

In summary, TP53 del may serve as a predictor for poor prognosis in pediatric B-ALL. In particular, children in the intermediate-risk group with positive MRD and TP53 del may require more aggressive treatment.

P=N/A, N=50, Recruiting, Rennes University Hospital | Not yet recruiting --> Recruiting

The patient has been in complete remission for 11 years following the diagnosis. We reviewed cases of B-ALL with double leukemogenic alterations and MYC-r with non-IG partners to understand the clinical outcome in these rare patients.

We observed that high expression was related to poor prognosis (p < 0.05). The increase in HMMR expression could be a potential early molecular prognostic marker and/or a new target in childhood B-ALL patients.

This dormant ALL subpopulation was effectively eradicated by dual pharmacologic inhibition of BCL-2 and JAK/STAT or SRC/ABL pathways, a clinically-relevant therapeutic strategy. Single cell-derived molecular signatures of this senescence and stem/progenitor-like subpopulation further predicted poor clinical outcomes associated with other high-risk genetic subtypes of childhood B-ALL and thus may have broader prognostic applicability beyond Ph-like ALL.

P=N/A, N=50, Not yet recruiting, Rennes University Hospital | Initiation date: Nov 2024 --> Feb 2025 | Trial primary completion date: Nov 2034 --> Feb 2035