GEO series
RAS pathway activation drives clonal selection and monocytic differentiation in FLT3 and BCL2 inhibitor resistance
GSE324062
Homo sapiens
Expression profiling by high throughput sequencing; Other
61 samples
Submitted 2026/04/01
Platform GPL34284
Summary
Despite efficacy of FLT3 and BCL2 inhibition in acute myeloid leukemia (AML), relapse limits survival. Mutation status and AML monocytic differentiation are implicated in resistance. On-treatment tumor evolution may select for genetically distinct clones or shifts in differentiation not resolvable by bulk sequencing. We performed multiomic single cell (SC) DNA/protein and RNA/protein profiling of patients treated on a clinical trial of the BCL2 inhibitor venetoclax and the FLT3 inhibitor gilteritinib (Ven/Git) to characterize immunophenotypic, transcriptional, and genetic clonal evolution on therapy. We found that while Ven/Gilt effectively eliminated FLT3 mutant clones, it selected for RAS mutations, RAS pathway activation and RAS-associated monocytic differentiation. In an in vitro model of monocytic differentiation associated with heightened RAS pathway activation, we demonstrated that MEK inhibition re-sensitized to Ven/Gilt. These data indicate RAS signaling is central to FLT3 and BCL2 inhibitor resistance, is tightly coupled to monocytic differentiation and can be overcome by RAS pathway inhibition.
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE324062_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 61 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1433374 and SRA study SRP681667. Searching any of these in the dataset finder brings you back here.
Study design
33 conditions, each sampled once — no replicated groups
Primary human samples, DNA; Patient 1 EOC ×3
Primary human samples, DNA; Patient 4 EOC ×3
Primary human samples, DNA; Patient 2 EOC ×2
Primary human samples, DNA; Patient 7 EOC ×2
Primary human samples, DNA; Patient 5 EOC ×2
Read from the first 40 of 61 sample titles: 33 distinct titles with little repetition. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM9567603 Primary human samples, DNA; Patients 2 pre-treatment and 7 pre-treatment
- GSM9567604 Primary human samples, cell surface proteins for immunophenotype; Patients 2 pre-treatment and 7 pre-tretment
- GSM9567605 Prrimary human samples, cell surface proteins for multiplexing; Patients 2 pre-treatment and 7 pre-treatment
- GSM9567606 Primary human samples, DNA; Patient 2 end of cycle (EOC) 1
- GSM9567607 Primary human samples, DNA; Patient 2 EOC 4
- GSM9567608 Primary human samples, DNA; Patient 2 EOC 7
- GSM9567609 Primary human samples, DNA; Patient 2 EOC 14, Patient 1 EOC 14, Patient 12 EOC1
- GSM9567610 Primary human samples, cell surface proteins for immunophenotype; Patient 2 EOC 14, Patient 1 EOC 14, Patient 12 EOC1
- GSM9567611 Primary human samples, cell surface proteins for multiplexing; Patient 2 EOC 14, Patient 1 EOC 14, Patient 12 EOC1
- GSM9567612 Primary human samples, DNA; patient 1 pre-treatment
- GSM9567613 Primary human samples, cell surface proteins for immunophenotype; patient 1 pre-treatment
- GSM9567614 Primary human samples, cell surface proteins for multiplexing; patient 1 pre-treatment
- GSM9567615 Primary human samples, DNA; Patient 1 EOC1
- GSM9567616 Primary human samples, DNA; Patient 1 EOC4
- GSM9567617 Primary human samples, DNA; Patient 1 EOC9
- GSM9567618 Primary human samples, DNA; Patient 11 pre-treatment and patient 11 EOC1
- GSM9567619 Primary human samples, cell surface proteins for immunophenotype; Patient 11 pre-treatment and patient 11 EOC1
- GSM9567620 Primary human samples, cell surface proteins for multiplexing; Patient 11 pre-treatment and patient 11 EOC1
- GSM9567621 Primary human samples, DNA; Patient 7 EOC1
- GSM9567622 Primary human samples, DNA; Patient 7 EOC3
- GSM9567623 Primary human samples, DNA; Patient 3 pre-treatment, Patient 8 pre-treatment, Patient 9 pre-treatment
- GSM9567624 Primary human samples, cell surface proteins for immunophenotype; Patient 3, 8, 9 pre-treatment
- GSM9567625 Primary human samples, cell surface proteins for multiplexing; Patient 3, 8, 9 pre-treatment
- GSM9567626 Primary human samples, DNA; Patient 3 EOC4, Patient 3 EOC7
- GSM9567627 Primary human samples,cell surface proteins for immunophenotype; Patient 3 EOC4, Patient 3 EOC7
- GSM9567628 Primary human samples,cell surface proteins for multiplexing; Patient 3 EOC4, Patient 3 EOC7
- GSM9567629 Primary human samples, DNA; Patient 4 pre-treatment, Patient 5 pre-treatment, Patient 12 pre-treatment
- GSM9567630 Primary human samples, cell surface proteins for immunophenotype; Patient 4, 5, 12 pre-treatment
- GSM9567631 Primary human samples, cell surface proteins for multiplexing; Patient 4, 5, 12 pre-treatment
- GSM9567632 Primary human samples, DNA; Patient 4 EOC1
- GSM9567633 Primary human samples, DNA; Patient 4 EOC4
- GSM9567634 Primary human samples, DNA; Patient 4 EOC6
- GSM9567635 Primary human samples, cell surface proteins for immunophenotype; Patient 4 EOC6
- GSM9567636 Primary human samples, cell surface proteins for multiplexing; Patient 4 EOC6
- GSM9567637 Primary human samples, DNA; Patient 5 EOC1
- GSM9567638 Primary human samples, DNA; Patient 5 EOC4
- GSM9567639 Primary human samples, DNA; Patient 6 pre-treatment
- GSM9567640 Primary human samples, cell surface proteins for immunophenotype; Patient 6 pre-treatment
- GSM9567641 Primary human samples, DNA; Patient 6 EOC1
- GSM9567642 Primary human samples, DNA; Patient 8 EOC1
+ 21 more — browse all 61 samples with per-sample file links →
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