What type of study is this?

This is a In Vitro Study study.

What question did this study set out to answer?

This research aims to map the epigenetic network in KMT2A-rearranged acute myeloid leukemia (AML) to identify vulnerabilities for combination therapy.

December 8, 2025Blood

A perturb-seq map of a differentiation hub reveals synergistic vulnerabilities in KMT2A-rearranged AML

View Full Paper

Ask AI

Bookmark

Authors

BCBrittany M. Curtiss

Discussion

Member takes

Overview

Pharmacological inhibition of synergistic epigenetic regulators improves leukaemia outcomes, indicating new therapeutic strategies.

Key Points

This research aims to map the epigenetic network in KMT2A-rearranged acute myeloid leukemia (AML) to identify vulnerabilities for combination therapy.
Conducted a Perturb-seq screen of 16 epigenetic regulators in MOLM-13 cell line
Used computational modeling to identify transcriptional modules and interactions
Validated findings through pharmacological assays and RNA-sequencing
Analyzed data from independent patient cohorts
Identified a core transcriptional module, the Myeloid Program, silenced by an epigenetic circuit
Simultaneous inhibition of KAT6A, Menin, and DOT1L resulted in significant Myeloid Program reactivation
High Myeloid Program activity correlated with improved overall survival in patients
Low Myeloid Program scores indicate vulnerability to PI3K/AKT/mTOR pathway inhibitors

Cite This Study

Brittany M. Curtiss (2025) studied this question.

synapsesocial.com/papers/69362f364fa91c937236d30d https://doi.org/10.1182/blood-2025-1707

View Full Paper

Ask AI

Bookmark

December 8, 2025Blood

A perturb-seq map of a differentiation hub reveals synergistic vulnerabilities in KMT2A-rearranged AML

View Full Paper

Ask AI

Bookmark

Authors

BCBrittany M. Curtiss

Discussion

Member takes

Overview

Pharmacological inhibition of synergistic epigenetic regulators improves leukaemia outcomes, indicating new therapeutic strategies.

Key Points

This research aims to map the epigenetic network in KMT2A-rearranged acute myeloid leukemia (AML) to identify vulnerabilities for combination therapy.
Conducted a Perturb-seq screen of 16 epigenetic regulators in MOLM-13 cell line
Used computational modeling to identify transcriptional modules and interactions
Validated findings through pharmacological assays and RNA-sequencing
Analyzed data from independent patient cohorts
Identified a core transcriptional module, the Myeloid Program, silenced by an epigenetic circuit
Simultaneous inhibition of KAT6A, Menin, and DOT1L resulted in significant Myeloid Program reactivation
High Myeloid Program activity correlated with improved overall survival in patients
Low Myeloid Program scores indicate vulnerability to PI3K/AKT/mTOR pathway inhibitors

Cite This Study

Brittany M. Curtiss (2025) studied this question.

synapsesocial.com/papers/69362f364fa91c937236d30d https://doi.org/10.1182/blood-2025-1707

Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

View Full Paper

Ask AI

Bookmark