What question did this study set out to answer?

To investigate the functional consequences of secondary KRAS mutations on disease latency, leukemic stem cell frequency, and transcriptomic rewiring in human KMT2A::MLLT3 acute myeloid leukemia.

August 20, 2026LeukemiaOpen Access

Modeling KRAS mutations in KMT2A::MLLT3 acute myeloid leukemia promotes leukemic progression and transcriptional rewiring

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Authors

NENayeli Esparza JDJoan Defrêne EBEva Bresson

Discussion

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Overview

Preclinical study reveals KRAS mutations accelerate disease progression and expand leukemic stem cells in KMT2A-rearranged acute myeloid leukemia, highlighting potential therapeutic targets.

Key Points

To investigate the functional consequences of secondary KRAS mutations on disease latency, leukemic stem cell frequency, and transcriptomic rewiring in human KMT2A::MLLT3 acute myeloid leukemia.
Introduced KRAS G13D or G12C mutations via CRISPR-Cas9 into human CD34+ cells transduced with KMT2A::MLLT3, followed by xenotransplantation into NSG-SGM3 mice.
Evaluated disease onset, secondary transplantation limiting dilution assays (LDA) for leukemic stem cell frequency, bulk and single-cell RNA sequencing, and clinical outcomes in the HARMONY cohort (N=22 KRAS-mutated cases).
Mice receiving KM3 + KRAS G13D developed leukemia 2.16 ± 0.65-fold faster and showed a >20-fold increase in leukemic stem cell frequency (1 in >17,000 vs. 1 in 360,000; p=0.0069).
Analysis of the HARMONY cohort of patients aged ≤60 years showed KRAS mutations significantly reduced median overall survival compared to wild-type disease (9.6 vs. 38.1 months; p=0.006).
Transcriptomic profiling identified 842 upregulated and 790 downregulated genes, along with the distinct emergence of an ALOX15-expressing conventional dendritic cell type 1-like subpopulation.

Cite This Study

Esparza et al. (2026) studied this question.

synapsesocial.com/papers/6a86b57f8a91293e6a1ccdf2 https://doi.org/10.1038/s41375-026-03112-z

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August 20, 2026LeukemiaOpen Access

Modeling KRAS mutations in KMT2A::MLLT3 acute myeloid leukemia promotes leukemic progression and transcriptional rewiring

View Full Paper

Ask AI

Bookmark

Authors

NENayeli Esparza JDJoan Defrêne EBEva Bresson

Discussion

Member takes

Overview

Preclinical study reveals KRAS mutations accelerate disease progression and expand leukemic stem cells in KMT2A-rearranged acute myeloid leukemia, highlighting potential therapeutic targets.

Key Points

To investigate the functional consequences of secondary KRAS mutations on disease latency, leukemic stem cell frequency, and transcriptomic rewiring in human KMT2A::MLLT3 acute myeloid leukemia.
Introduced KRAS G13D or G12C mutations via CRISPR-Cas9 into human CD34+ cells transduced with KMT2A::MLLT3, followed by xenotransplantation into NSG-SGM3 mice.
Evaluated disease onset, secondary transplantation limiting dilution assays (LDA) for leukemic stem cell frequency, bulk and single-cell RNA sequencing, and clinical outcomes in the HARMONY cohort (N=22 KRAS-mutated cases).
Mice receiving KM3 + KRAS G13D developed leukemia 2.16 ± 0.65-fold faster and showed a >20-fold increase in leukemic stem cell frequency (1 in >17,000 vs. 1 in 360,000; p=0.0069).
Analysis of the HARMONY cohort of patients aged ≤60 years showed KRAS mutations significantly reduced median overall survival compared to wild-type disease (9.6 vs. 38.1 months; p=0.006).
Transcriptomic profiling identified 842 upregulated and 790 downregulated genes, along with the distinct emergence of an ALOX15-expressing conventional dendritic cell type 1-like subpopulation.

Cite This Study

Esparza et al. (2026) studied this question.

synapsesocial.com/papers/6a86b57f8a91293e6a1ccdf2 https://doi.org/10.1038/s41375-026-03112-z

View Full Paper

Ask AI

Bookmark