Oncofusion

start / graph / absence-q124-k562-is-still-the-only-fusion-free-line-in-gse260742-with-a-menin-inhibitor-arm

Analysisstrong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.Q124-the-timecourse-and-the-pcgf1-knockout

Verified against the live records rather than inherited: HUDEP-2 and mESC each carry a DMSO and an SGC0946 H3K79me2 sample and no VTP-50469 sample, so K562 remains the only fusion-free line in GSE260742 able to score a menin-inhibitor effect - and cycle 82's request for a second and third fusion-free line cannot be met from this series

also called the second fusion-free line does not exist here · HUDEP-2 and mESC are SGC-only

The strongest challenge to this project's account of how the menin drug works rests on one cell line without the fusion. Two other fusion-free cell lines are in the same dataset, but each was only treated with the other drug, so neither can be used to check the result. That check needs data nobody has deposited here.

The same thing, for a scientist

**Cycle 82 named a second and third fusion-free line as its next step 2**, calling the K562 result *"the load-bearing control for the strongest threat in the queue"*: K562 carries no KMT2A fusion and gives `V = 0.8291` and `F = 0.1831`, inside the fusion-bearing murine range, with pre-registered refutation R2 missing by 0.0057. **This beat's dispatch brief asserted that GSE260742 cannot supply the extra lines. Verified against the live records and the brief is right** [E1]. | fusion-free line in GSE260742 | H3K79me2 DMSO | H3K79me2 SGC0946 5 uM | **H3K79me2 VTP-50469** | |---|---|---|---| | **K562** (`cell line: K562`) | GSM8123349 | GSM8123351 | **GSM8123353** | | **HUDEP-2** (`cell line: HUDEP-2`) | GSM8123344 | GSM8123346 | **ABSENT** | | **mESC** (`cell line: mESC`) | GSM8123356 | GSM8123358 | **ABSENT** | The HUDEP-2 and mESC arms consist of an input, an H2AK119ub DMSO, an H3K79me2 DMSO, an H2AK119ub SGC0946 and an H3K79me2 SGC0946 - five samples each, **no menin inhibitor anywhere in either**. A `V` requires a VTP-against-DMSO pair, so **neither line can score any criterion about a menin inhibitor**, and the extra fusion-free replication cycle 82 asked for is a `never-measured` absence of this deposit. **Why it is worth an entry rather than a line in a memo.** The K562 threat is, on cycle 82's own assessment, *"the most substantial threat the drug's mechanism story has taken in this corpus"*, and its stated weakness is n = 1. **A reader looking at a 158-sample series containing three fusion-free lines would reasonably assume n = 3 is available for one download each.** It is not, and recording that stops the next beat from spending the downloads to find out. The brief's accession pairs were exactly right and are reproduced above from this beat's own read.

Facts and figures
seriesGSE260742
consequencecycle 82's next-step 2 (a second and third fusion-free line) cannot be met from this series; K562 stays n = 1 for the strongest standing threat to the drug's mechanism story
the opportunity that does existHUDEP-2 and mESC each carry an H2AK119ub DMSO/SGC0946 pair (GSM8123343/345 and GSM8123355/357), so a fusion-free test of the DOT1L-inhibitor half of the paper's PRC1.1-antagonism model is four downloads and nobody has asked for it
absence classnever-measured
absence class notenever-measured IN THIS SERIES. The two additional fusion-free lines were cultured and ChIPed for this very paper and simply never given the menin inhibitor, so the samples do not exist and no re-analysis can create them. Closing it needs either a wet experiment or a cross-series search that this beat did not run; the cross-series search is the cheaper first step and is named in the open questions.
absence class assigned2026-09-23 (Q124)
fusion free lines present
{
  "K562": "DMSO, SGC0946 and VTP-50469 H3K79me2 - complete",
  "HUDEP-2": "DMSO and SGC0946 only, no VTP arm in any channel",
  "mESC": "DMSO and SGC0946 only, no VTP arm in any channel"
}
How this could bite us back
  • The strongest standing threat to the menin inhibitor's mechanism story rests on one cell line, and this entry establishes that the series it came from cannot supply a second. Anyone treating the K562 result as robust is treating an n = 1 measurement, 0.0057 from failing its own pre-registered refutation, as settled.
  • The reverse reading is also available and is less comfortable: if no second fusion-free line can be found anywhere, the threat stays permanently at n = 1 and the corpus has to carry it as an unresolvable caveat on every H3K79me2 statement about this drug.
Still open
  1. Has any other deposit measured H3K79me2 under a menin inhibitor in a cell line with no KMT2A fusion? No cross-series GEO query was run, and this is the cheapest way to turn the K562 result from n = 1 into n = 2. It should precede any proposal for new wet work.
  2. Do HUDEP-2 and mESC show the same SGC0946 floor rise that the four murine cultures show? Four downloads, and it would test whether the DOT1L inhibitor's compartmental signature is a property of the drug or of KMT2A-rearranged chromatin.
  3. K562's own drug-to-vehicle non-zero bin count ratio has never been checked, and this beat measured that a top-set share ratio is confounded with library enrichment. Q122 binned all four K562 files and its committed results.json carries their diagnostics, so the check is a file lookup - and the K562 result is the load-bearing control for the strongest threat in this corpus.
Every source behind this entry (1)
  1. E1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.dataset

    In GSE260742's 158 per-sample records, the HUDEP-2 arm is GSM8123342 (DMSO input), GSM8123343 (DMSO H2AK119ub), GSM8123344 (DMSO H3K79me2), GSM8123345 (SGC0946 5 uM H2AK119ub) and GSM8123346 (SGC0946 5 uM H3K79me2), and the mESC arm is GSM8123354, GSM8123355, GSM8123356, GSM8123357 and GSM8123358 in the same five roles; neither arm contains any VTP-50469 sample of any channel, so neither line can supply a menin-inhibitor share ratio, and K562 (GSM8123349 DMSO, GSM8123351 SGC0946, GSM8123353 VTP-50469, all H3K79me2, plus GSM8123347 input) remains the only line in the series with no KMT2A fusion and a complete three-arm H3K79me2 set.

    What this evidence cannot show

    This bounds the DEPOSIT and not the field: no cross-series GEO sweep for a menin-inhibitor H3K79me2 experiment in a fusion-free line was run, so 'a second fusion-free line does not exist' is true of GSE260742 only. 'Fusion-free' here means no KMT2A fusion: K562 carries BCR::ABL1 b3a2 per Cellosaurus CVCL_0004, which Q122 recorded, so the line is not fusion-free in general and the K562 result's own caveat about that stands unchanged. HUDEP-2 and mESC are not fusion-free COMPARATORS for a leukaemia claim in any case - one is an immortalised erythroid progenitor line and the other is embryonic stem cells - so even a VTP arm in them would have been a weaker control than a second leukaemia line. This beat did not download or bin any HUDEP-2 or mESC file; the claim is from the records.

    Evidence that argues against this (1)
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