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December 8, 2025BloodOpen Access

Modeling of a hyper-inflammatory hematopoietic niche ex vivo reveals a multi-step process driving CAR T- cell associated myeloid leukemia in multiple myeloma

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Authors

SHSeungbin HanAHAnn-Sophie HainoldTSTorsten Steinbrunn

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Overview

Ex vivo modeling reveals CAR T-cell inflammation promotes myeloid leukemia in multiple myeloma, indicating clonal expansion dynamics.

Key Points

  • This research aims to elucidate the mechanisms driving CAR T-cell associated myeloid leukemia in multiple myeloma.
  • Developed TP53-knockout THP-1 cells using CRISPR-Cas9 for modeling.
  • Assessed the impact of melphalan and inflammatory cytokines on clonal dynamics in vitro.
  • Used peripheral blood mononuclear cells from patients to analyze clonal expansion through variant allele frequency estimation.
  • TP53-KO clones showed resistance to melphalan with a significant IC50 shift.
  • IL-6 stimulation resulted in a ~6-fold increase in clonal expansion after 14 days of ex vivo cultivation.
  • The data support a model of leukemogenesis driven by mutagenic and inflammatory signals.

Cite This Study

Han et al. (2025) studied this question.

synapsesocial.com/papers/69362f5a4fa91c937236db63https://doi.org/10.1182/blood-2025-2152
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