CFCM Daily Radar — In Vivo CAR-NK, PDGFRA Basophilia and AML Mitophagy

Paper of the Day — In vivo engineering of CAR-NK cells

Peer-reviewed original research

Yuang Chen, Julia Monkovic, Haseeb Mughal, Binlong Chen and colleagues. In vivo engineering of CAR natural killer cells for immunotherapy using ligand-directed lipid nanoparticles. Nature Biotechnology. Published 13 October 2026. DOI: 10.1038/s41587-026-03310-1.

The investigators delivered CAR-encoding mRNA directly to NK cells with ligand-directed lipid nanoparticles. In mouse experiments, leading formulations produced high NK-cell transfection, CD19-directed CAR-NK generation and B-cell depletion; antitumour activity was also demonstrated in humanized models. This remains preclinical research.

Why it matters to CFCM: if immune cells are engineered inside the patient, clinical monitoring may need to quantify CAR-positive NK cells, persistence, target-cell depletion and function longitudinally rather than relying only on conventional ex vivo product-release assays.

Clinical case — PDGFRA-rearranged myeloid neoplasm with basophilia

Peer-reviewed case report

Anne-Cecilia van Marle and Evan Bowen. Myeloid neoplasm with PDGFRA rearrangement presenting in blast-phase with basophilia. Journal of Hematopathology. DOI: 10.1007/s12308-026-00743-0.

Flow cytometry identified a myeloblast population and a separate CD123-positive basophil population in a diagnostically complex case. Molecular testing ultimately identified FIP1L1::PDGFRA despite absence of the expected eosinophilia.

Why it matters: morphology, flow cytometry and molecular testing must be integrated. CD123 positivity, increased mast cells or unusual basophils should not be converted into a diagnosis in isolation.

CFCM placement: News → Haematological Malignancies; Academy → Myeloid Neoplasms; Troubleshooting → Unusual Immunophenotypes.

AML Technology Radar — Mitophagy and venetoclax sensitivity

Peer-reviewed mechanistic research

Inhibition of PHB2/PINK1-mediated mitophagy potentiates venetoclax activity in acute myeloid leukemia. Leukemia. DOI: 10.1038/s41375-026-03160-5.

The study links PINK1/PHB2-mediated mitochondrial quality control to experimental venetoclax resistance. Genetic or pharmacological disruption increased drug sensitivity in preclinical systems. No validated clinical flow-cytometric predictor is established.

CFCM placement: Intelligence → Technology Radar; Academy → Functional Cytometry.

MRD interpretation — Negative disease does not mean safe treatment

Peer-reviewed correspondence reporting a retrospective case series

Venetoclax combined with olverembatinib and prednisone as a frontline therapeutic strategy for Philadelphia chromosome-positive mixed-phenotype acute leukemia. Blood Research. DOI: 10.1007/s44313-026-00180-z.

Five patients achieved complete remission and flow-MRD negativity, yet two later died after severe myelosuppression and pulmonary infection. The case series is small and uncontrolled but provides a clear educational distinction between disease-response measurement and treatment safety.

CFCM placement: Academy → MRD Interpretation; News → Acute Leukaemias.

Evidence note

The CAR-NK work is preclinical; the PDGFRA publication is a single case; the mitophagy study is mechanistic; and the MPAL evidence is a five-patient retrospective case series. None is presented as a validated new clinical standard.