GEO series
The cellular hierarchy of acute myeloid leukemia informs personalized treatment
GSE272681
Homo sapiens
Expression profiling by high throughput sequencing
108 samples
Submitted 2024/07/20
Platform GPL24676
Summary
Acute myeloid leukemia (AML) is characterized by malignant myeloid precursors that span a cellular hierarchy from dedifferentiated leukemic stem cells to mature blasts. While the diagnostic and prognostic importance of AML blast maturation is increasingly recognized, personalized therapies are currently not tailored to a patient’s individual makeup of this cellular hierarchy. In this study, we use multiplexed image-based ex vivo drug screening (pharmacoscopy) to systematically quantify the drug sensitivity across the cellular hierarchy of AML patients. We analyzed 174 prospective and longitudinal patient samples from 44 newly diagnosed AML patients, which indicated that differences in the AML hierarchy significantly identified poor responses to first-line therapy, outperforming European LeukemiaNet (ELN) criteria. Critically, drug response profiling across the AML hierarchy of each patient improved the accuracy of predicting patient response to first-line therapy (AUC 0.91), and revealed alternative individualized treatment options targeting the complete AML hierarchy of non-responding patients. We confirmed these findings in an independent cohort of 26 relapsed/refractory AML patients, for whom pan-hierarchy response profiling improved response predictions post hoc. Overall, our results quantify the clinical importance of therapeutically targeting the complete cellular hierarchy of newly diagnosed AML, and identify multiplexed image-based ex vivo drug screening to enable quantification and targeting of the AML maturation hierarchy for improved personalized treatment.
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE272681_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 108 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1137956 and SRA study SRP521084. Searching any of these in the dataset finder brings you back here.
Study design
37 conditions, each sampled once — no replicated groups
Patient AML012, bonemarrow, time point 3, ×2
Patient AML013, blood, time point 3, ×2
Patient AML014, blood, time point 2, ×2
Read from the first 40 of 108 sample titles: 37 distinct titles with little repetition. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM8409070 Patient AML008, bonemarrow, time point 2, Batch 1
- GSM8409071 Patient AML008, blood, time point 2, Batch 1
- GSM8409072 Patient AML009, bonemarrow, time point 1, Batch 1
- GSM8409073 Patient AML009, blood, time point 3, Batch 1
- GSM8409074 Patient AML010, bonemarrow, time point 2, Batch 1
- GSM8409075 Patient AML010, blood, time point 2, Batch 1
- GSM8409076 Patient AML010, blood, time point 3, Batch 1
- GSM8409077 Patient AML012, bonemarrow, time point 3, Batch 1
- GSM8409078 Patient AML012, blood, time point 1, Batch 1
- GSM8409079 Patient AML012, blood, time point 3, Batch 1
- GSM8409080 Patient AML013, bonemarrow, time point 3, Batch 1
- GSM8409081 Patient AML013, blood, time point 1, Batch 1
- GSM8409082 Patient AML013, blood, time point 3, Batch 1
- GSM8409083 Patient AML014, bonemarrow, time point 2, Batch 1
- GSM8409084 Patient AML014, blood, time point 2, Batch 1
- GSM8409085 Patient AML015, bonemarrow, time point 1, Batch 1
- GSM8409086 Patient AML018, blood, time point 1, Batch 1
- GSM8409087 Patient AML012, bonemarrow, time point 3, Batch 2
- GSM8409088 Patient AML013, blood, time point 3, Batch 2
- GSM8409089 Patient AML014, blood, time point 2, Batch 2
- GSM8409090 Patient AML015, blood, time point 3, Batch 2
- GSM8409091 Patient AML018, bonemarrow, time point 3, Batch 2
- GSM8409092 Patient AML019, bonemarrow, time point 2, Batch 2
- GSM8409093 Patient AML019, blood, time point 1, Batch 2
- GSM8409094 Patient AML019, blood, time point 3, Batch 2
- GSM8409095 Patient AML020, bonemarrow, time point 2, Batch 2
- GSM8409096 Patient AML020, bonemarrow, time point 3, Batch 2
- GSM8409097 Patient AML020, blood, time point 1, Batch 2
- GSM8409098 Patient AML020, blood, time point 2, Batch 2
- GSM8409099 Patient AML020, blood, time point 3, Batch 2
- GSM8409100 Patient AML021, bonemarrow, time point 1, Batch 2
- GSM8409101 Patient AML021, bonemarrow, time point 2, Batch 2
- GSM8409102 Patient AML021, bonemarrow, time point 3, Batch 2
- GSM8409103 Patient AML021, blood, time point 1, Batch 2
- GSM8409104 Patient AML021, blood, time point 2, Batch 2
- GSM8409105 Patient AML022, bonemarrow, time point 1, Batch 2
- GSM8409106 Patient AML022, blood, time point 1, Batch 2
- GSM8409107 Patient AML023, bonemarrow, time point 2, Batch 2
- GSM8409108 Patient AML023, bonemarrow, time point 3, Batch 2
- GSM8409109 Patient AML023, blood, time point 2, Batch 2
+ 68 more — browse all 108 samples with per-sample file links →
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