B Acute Lymphoblastic Leukemia

Blinatumomab was administered after one cycle of high-dose methotrexate/cytarabine, resulting in MRD negativity after one cycle...Inotuzumab ozogamicin induced a second hematological remission with MRD negativity, although disease control was not durable. This case highlights the importance of repeat immunophenotypic and cytogenetic assessment at relapse after blinatumomab treatment.

Using B-ALL cell lines and patient-derived xenografts, we show that FATP2-expressing TP53-mutant B-ALL resistance to CAR-T is dependent on exogenous lipid uptake to fuel fatty acid oxidation (FAO) and cell survival, which can be pharmacologically targeted through inhibition of neutral lipolysis and CPT1. These findings identify FATP2-mediated fatty acid uptake and downstream FAO as a potential target to improve existing CAR-T efficacy in human B-ALL.

These findings support POD12 and POD24 as clinically practical, data-driven landmarks for identifying patients with adverse survival outcomes. They may also inform the exploratory evaluation of 1-year and 2-year progression-free survival as hypothesis-generating candidate early trial endpoints, pending prospective validation.

P1/2, N=91, Recruiting, Curocell Inc. | Trial completion date: Feb 2028 --> Sep 2030 | Trial primary completion date: May 2023 --> Aug 2030

P1, N=18, Not yet recruiting, M.D. Anderson Cancer Center

Reporter assays confirmed direct targeting of both genes. miR-326 attenuates MDR in pALL through direct suppression of ABCA2 and YY1, highlighting its potential as a therapeutic target for overcoming chemoresistance in pediatric B-ALL.

Collectively, our results identify, for the first time, PXDN, TCF4 and TSPAN7 as differentially expressed genes in ALL and highlight the usefulness of integrative transcriptomic analyses across independent datasets. While limited by small-scale experimental validation and reliance on computational predictions, this study provides a framework for prioritising candidate genes and generates testable hypotheses regarding their potential involvement in leukaemia-associated molecular pathways.

The patient was treated using a standard risk ALL protocol and is in remission for two years. This report demonstrates how comprehensive genomic profiling with OGM and long-read sequencing can help resolve atypical findings from conventional methods, enable proper sub-classification and potentially inform risk assessment in relapsed or drug-resistant disease.

Patients with lineage switch have dismal outcomes and optimal therapies remain unknown, thus there is a large unmet need to better understand the biology, define the diagnosis, and determine the therapeutic approaches to lineage switch. Here, we address these needs providing a review of the current biology of lineage switch, the relationship to different genetic subtypes and present definitions and recommendations for immunophenotypic and molecular monitoring.

Notably, Natalizumab (NTZ) - an FDA/EMA-approved monoclonal antibody targeting ITGA4 - delayed leukemia progression and potentiated the efficacy of standard-of-care chemotherapy in KMT2A-r B-ALL patient-derived xenograft (PDX) models. Collectively, our findings define a novel ITGA4-NG2 signaling axis that drives the aggressiveness of KMT2A-r B-ALL and support the repurpose of NTZ as an adjuvant therapeutic strategy for this high-risk leukemia subtype.

Aleukemic/low PB lymphoblast presentation of B-ALL is associated with unique clinicopathological features that overlap with non-malignant disorders. A high degree of clinical suspicion and careful review of PB flow cytometry data are required for timely diagnosis.