Single cell proteogenomic sequencing identifies a relapse‐fated AML subclone carrying <i>FLT3</i>‐ITD with CN‐LOH at chr13q
Bibliographic record
Abstract
Abstract Internal tandem duplication of the Feline McDonough Sarcoma (FMS)‐like tyrosine kinase 3 ( FLT3 ‐ITD) is one of the most clinically relevant mutations in acute myeloid leukemia (AML), with a high FLT3 ‐ITD allelic ratio (AR) (≥0.5) being strongly associated with poor prognosis. FLT3 ‐ITDs are heterogeneous, varying in size and location, with some patients having multiple FLT3 ‐ITDs. Bulk cell‐based approaches are limited in their ability to reveal the clonal structure in such cases. Using single‐cell proteogenomic sequencing (ScPGseq), we attempted to identify a relapse‐fated subclone in an AML case with mutations in WT1 , NPM1 , and FLT3 tyrosine kinase domain and two FLT3 ‐ITDs (21 bp and 39 bp) (low AR) at presentation, then relapsed only with WT1 and NPM1 mutations and one FLT3 ‐ITD (high AR). This relapse‐fated subclone at presentation (∼2.1% of sequenced cells) was characterized by the presence of a homozygous 21 bp FLT3 ‐ITD resulting from copy neutral loss of heterozygosity (CN‐LOH) of chr13q and an aberrant, immature myeloid cell surface signature, contrast to the cell surface phenotype at presentation. In contrast to results from multicolor flow‐cytometry, ScPGseq not only enabled the early detection of rare relapse‐fated subclone showing immature myeloid signature but also highlighted the presence of homozygous 21 bp FLT3 ‐ITDs in the clone at presentation.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".