Bounding an absence the graph already asserts: the H3K79me2 decay half-life, counted, dated and controlled - and why three of the six hits are about the drug's half-life
also called H3K79me2 half-life · H3K79 turnover · mark decay kinetics
Three entries in this graph say nobody has measured how fast the H3K79 tag fades once the enzyme that writes it is blocked, and none of them ran a search to check. A dated, controlled search confirms it - with a trap worth carrying away: in a DOT1L literature the word 'half-life' almost always means the drug's, not the tag's.
The same thing, for a scientist
Three entries already assert this absence without a query: `mechanism-fusion-dependency-reversibility-kinetics` records `h3k79me2_decay_halflife: "not reported anywhere in the indexed literature"`; `mechanism-h3k79-turnover-and-dilution` names 'cell divisions of continuous DOT1L inhibition required to clear H3K79me2 from HOXA9' as its unmeasured number; and `exp-h3-3-turnover-at-fusion-targets-under-dot1l-inhibition` is designed to measure it. **This entry does not restate the biology or re-propose the experiment - it supplies the bound those three lack.** Measured 2026-09-20: `H3K79[tiab] AND (half-life[tiab] OR "decay rate"[tiab] OR turnover[tiab])` returns **6 records, of which 0 report a decay constant for the mark** [E1]. The identical query shape returns **33** for H3K27me3 and **7** for H3K9me2, so the instrument demonstrably returns ones [E1]. **Three of the six hits are about a half-life that is not the mark's**: one is the DOT1L inhibitor's residence time [E2] and two are pinometostat's plasma pharmacokinetics [E3]. That is the transferable finding - in this literature *half-life* is a property of the drug unless proved otherwise, which is brief rule 71's shape operating on a physical constant rather than on a gene symbol.
The measurement, with the control
| query (PubMed, 2026-09-20) | count | on topic after title-check |
|---|---|---|
H3K79[tiab] AND (half-life[tiab] OR "decay rate"[tiab] OR turnover[tiab]) | 6 | 0 |
H3K27me3[tiab] AND (…same three terms…) - positive control, identical shape | 33 | not checked; >0 is the point |
H3K9me2[tiab] AND (…same three terms…) - second positive control | 7 | not checked |
H3K79[tiab] alone - operand check | 509 | - |
H3K79[tiab] AND (MLL OR KMT2A) AND (…five kinetic terms…) | 1 | 0 |
H3K27me3[tiab] AND (MLL OR KMT2A) AND (…five kinetic terms…) - control on the three-clause shape | 0 | - |
Two shapes, and only one of them is controlled. The two-clause shape returns 33 and 7 on control marks, so a zero from it is interpretable. The three-clause shape returns 0 for the control as well, so it has no demonstrated positive and nothing may be concluded from its result. Brief rule 67 says a control on a different shape licenses nothing; this entry therefore rests on the two-clause measurement and records the three-clause one as uninterpretable rather than as corroboration.
The six records, and why none of them is the number
Every one was title-checked and two were abstract-checked:
| PMID | what its 'half-life'/'turnover' actually refers to |
|---|---|
| 22978415 | the inhibitor's dissociation rate and residence time on DOT1L 2 |
| 26645404, 24415392 | pinometostat's plasma metabolism and disposition 3 |
| 30472189 | nucleosome turnover shaping methylation patterns genome-wide, not H3K79me2 decay after enzyme loss |
| 33190371 | a review of chromatin barriers to reprogramming |
| 38370658 | DOT1L and MYC/Mondo degradation on chromatin (preprint) |
The vocabulary trap. In this literature the word half-life is overwhelmingly a pharmacokinetic term. A reader scanning the six hits sees three papers that appear to be about DOT1L kinetics and are about the drug. This is brief rule 71's shape - a pathway named by its drug - operating on a physical constant rather than on a gene symbol.
What this entry does not do, and where the biology lives
This is a bounding measurement, not a mechanism entry, and the graph already holds the mechanism and the experiment:
- Why the mark can only be diluted -
mechanism-h3k79-demethylation-contested(no convincing eraser; the KDM2B claim is one laboratory, two papers, unreplicated) andmechanism-h3k79-turnover-and-dilution(nucleosome turnover sets valency). - The experiment that would produce the number -
exp-h3-3-turnover-at-fusion-targets-under-dot1l-inhibition, SNAP-tag H3.3 quench-chase-pulse in KMT2A::AFF1 lines, cycling and arrested. - Why the number is load-bearing for the chain -
mechanism-kmt2a-fusion-causal-chain, where the arrow from H3K79me2 to programme collapse cannot be measured at all without it, anddrug-pinometostat, where 2 complete remissions in 51 adults 4 cannot be read as a mechanism failure until the schedule question is settled.
What it adds is the bound. All three of the entries above assert the absence in prose or in a data field; none carries a query, a date, a count or a control. An unbounded 'nobody has measured this' is the failure mode this project's own standard names - localization-nuclear-lamina-lads-kmt2a-r states it as a counted negative with a date rather than an unbounded 'nobody has looked'. Three entries were relying on each other for a claim none of them had checked.
| absence claim | No published study reports a decay half-life or decay rate constant for H3K79me2 in any system. |
|---|---|
| date measured | 2026-09-20 |
| tool | PubMed E-utilities esearch |
| all six hits title checked | true |
| why it matters | sets the interval between DOT1L target engagement and transcriptional effect, and therefore the schedule any DOT1L trial should have used |
| chain | mechanism-kmt2a-fusion-causal-chain |
| absence class | never-measured |
| absence class basis | A decay half-life requires a timecourse after an acute perturbation; none has been reported. |
| absence class assigned | 2026-09-21 (cycle 47, king) |
queries — the numbers behind the chart
[
{
"q": "H3K79[tiab] AND (half-life[tiab] OR \"decay rate\"[tiab] OR turnover[tiab])",
"count": 6,
"on_topic": 0
},
{
"q": "H3K27me3[tiab] AND (half-life[tiab] OR \"decay rate\"[tiab] OR turnover[tiab])",
"count": 33,
"role": "positive control, identical shape"
},
{
"q": "H3K9me2[tiab] AND (half-life[tiab] OR \"decay rate\"[tiab] OR turnover[tiab])",
"count": 7,
"role": "positive control, identical shape"
},
{
"q": "H3K79[tiab]",
"count": 509,
"role": "operand check"
},
{
"q": "H3K79[tiab] AND (MLL[tiab] OR KMT2A[tiab]) AND (half-life[tiab] OR \"decay rate\"[tiab] OR turnover[tiab] OR washout[tiab] OR kinetics[tiab])",
"count": 1,
"on_topic": 0,
"role": "three-clause shape - UNINTERPRETABLE, control returns 0"
},
{
"q": "H3K27me3[tiab] AND (MLL[tiab] OR KMT2A[tiab]) AND (half-life[tiab] OR \"decay rate\"[tiab] OR turnover[tiab] OR washout[tiab] OR kinetics[tiab])",
"count": 0,
"role": "failed control for the three-clause shape"
},
{
"q": "(pinometostat[tiab] OR EPZ-5676[tiab]) AND (washout[tiab] OR \"half-life\"[tiab] OR recovery[tiab])",
"count": 2,
"on_topic": 0
}
]strings tried
[ "half-life", "decay rate", "turnover", "washout", "kinetics" ]
strings not tried
[ "dilution rate", "metabolic labelling", "SILAC", "heavy methyl", "pulse-chase" ]
hits
{
"22978415": "inhibitor residence time",
"24415392": "drug PK",
"26645404": "drug PK",
"30472189": "nucleosome turnover",
"33190371": "review",
"38370658": "MYC/Mondo degradation"
}relation to existing entries
{
"bounds_the_assertion_in": [
"mechanism-fusion-dependency-reversibility-kinetics",
"mechanism-h3k79-turnover-and-dilution",
"exp-h3-3-turnover-at-fusion-targets-under-dot1l-inhibition"
],
"does_not_duplicate": "the loss mechanism (mechanism-h3k79-turnover-and-dilution), the eraser question (mechanism-h3k79-demethylation-contested) or the experimental design (exp-h3-3-turnover-at-fusion-targets-under-dot1l-inhibition)"
}- If the mark's half-life is long, a DOT1L inhibitor's apparent failure is a schedule failure, and the class would have been abandoned for the wrong reason.
- If it is short, then sustained H3K79me2 in a treated patient indicates residual enzyme activity rather than slow decay, and the correct response is more drug rather than more time - the opposite clinical decision from the same observation.
- An absence that three entries assert and none has bounded is exactly the kind of claim a reviewer falsifies in one query; the risk here is to the argument, not to a patient.
- Has the constant been measured under a nucleosome-turnover vocabulary rather than a mark vocabulary? This absence is bounded by mark-name strings and would not see such a paper; PMID 30472189 is the nearest case.
- How many other unbounded absence assertions in this graph are held in data fields rather than in evidence claims, where no confidence tier and no caveat attaches to them?
- Would adding 'dilution rate', 'pulse-chase' and 'metabolic labelling' to the string set change the count? Those were not tried and are named here so the next reader does not repeat the same three.
- E1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
PubMed on 2026-09-20 returns 6 records for H3K79 combined with half-life, decay rate or turnover in title/abstract, none of which reports a decay constant for the mark; the identical query shape returns 33 for H3K27me3 and 7 for H3K9me2, and H3K79 alone returns 509.
PubMed E-utilities esearch, run 2026-09-20 by the Q52 spine beat; counts and querytranslation strings recorded verbatim · Oncofusion knowledge graph (internal measurement) 2026What this evidence cannot show
A counted, dated, positively controlled absence over ONE vocabulary. Strings tried: `half-life`, `decay rate`, `turnover`, and in the three-clause form also `washout` and `kinetics`; not tried: `dilution rate`, `k_off` for the mark, `SILAC`, `metabolic labelling`, `heavy methyl`. The mark may have been measured in a paper that frames it as histone methylation turnover generally rather than naming H3K79, which is exactly the complex-form failure brief rule 64 describes. The three-clause query shape has no demonstrated positive control and nothing is concluded from it.
Evidence that argues against this (1)
- Nucleosome turnover has been measured genome-wide and shown to regulate histone methylation patterns, so the relevant kinetics may exist in the literature under a nucleosome-centred rather than a mark-centred vocabulary; an absence bounded by mark-name strings cannot see it. Chory EJ et al. 2019
- E2strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
In an aminonucleoside DOT1L inhibitor series, improvements in affinity and selectivity are driven entirely by a diminished dissociation rate constant, giving long residence times for the enzyme-inhibitor complex, and these residence times correlate with effects on intracellular H3K79 methylation.
Conformational adaptation drives potent, selective and durable inhibition of the human protein methyltransferase DOT1L. · Basavapathruni A, Jin L, Daigle SR, Majer CR, et al. · Chem Biol Drug Des 2012What this evidence cannot show
Abstract read 2026-09-20. This is the paper a naive reader of the six hits would take as the H3K79 kinetics paper. The measured time constants are the INHIBITOR's, and the intracellular H3K79 effect is reported as a correlation rather than as a decay measurement.
Evidence that argues against this (1)
- The correlation between inhibitor residence time and intracellular H3K79 methylation loss does bound the mark's decay from one side: methylation fell measurably within the assay windows used, so the half-life is not arbitrarily long. It is a bound, not a number. Stein EM et al. 2018
- E3strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
The pinometostat literature that PubMed returns under 'half-life' consists of nonclinical and cross-species pharmacokinetics and disposition studies of the compound.
Metabolism and disposition of the DOT1L inhibitor, pinometostat (EPZ-5676), in rat, dog and human. · Waters NJ, Smith SA, Olhava EJ, Duncan KW, et al. · Cancer Chemother Pharmacol 2016What this evidence cannot show
Abstract-level check 2026-09-20 on both PK papers (26645404, 24415392). Cited here only to characterise what the query returns; neither paper is being used for a biological claim.
Evidence that argues against this (1)
- Drug PK is not irrelevant to the missing constant: a compound with a short plasma half-life administered by continuous infusion was precisely the design used clinically, which implies the developers had a view of the required exposure duration - but no mark-decay measurement supporting that view is published. Stein EM et al. 2018
- E4established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper
Pinometostat in 51 adults with acute leukaemia reduced H3K79 methylation as intended but produced only two complete remissions, both in t(11;19), with the maximum tolerated dose not reached.
The DOT1L inhibitor pinometostat reduces H3K79 methylation and has modest clinical activity in adult acute leukemia. · Stein EM, Garcia-Manero G, Rizzieri DA, Tibes R, et al. · Blood 2018What this evidence cannot show
Abstract read 2026-09-20. Adults, relapsed/refractory, single agent. Cited here for the specific point that a pharmacodynamic effect on the mark was achieved while clinical effect was modest, which is what makes the decay constant decision-relevant.
Evidence that argues against this (1)
- Treatment-emergent resistance to pinometostat arose in five KMT2A-rearranged lines without DOT1L mutation, in one case through ABCB1 efflux - so modest clinical activity has at least one explanation that has nothing to do with mark kinetics. Olsen SN et al. 2022
- E5established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper
Combined DOT1L and menin inhibition resembles outright MLL::AF9 degradation and releases the oncoprotein from chromatin globally, whereas either single agent has more modest effects.
MLL::AF9 degradation induces rapid changes in transcriptional elongation and subsequent loss of an active chromatin landscape. · Olsen SN, Godfrey L, Healy JP, Choi YA, et al. · Mol Cell 2022What this evidence cannot show
Abstract read 2026-09-20. Murine/human MLL::AF9 degron system. Cited for the combination-timing argument only; the paper does not measure H3K79me2 decay kinetics either.
Evidence that argues against this (1)
- A menin plus DOT1L combination was already reported to enhance differentiation and killing while sparing normal haematopoiesis, so the combination rationale does not depend on the degron result and would survive a different answer on mark kinetics. Dafflon C et al. 2017
re-run and survives: the three H3K79me2-plus-kinetics records the original three-clause shape could not interpret are all off topic on title check
answers this entry's own open question - how many unbounded absence assertions sit in data fields rather than evidence claims - with 182 carrying the field and 115 carrying only the token
SURVIVES: re-bound from abstract level to 12.4 M full texts; the single phrase hit states no value and cites a 2010 review
bounds the unmeasured number from one side: three days after DOT1L occupancy falls to 0.22 at the fusion's own MOLM13 sites, H3K79me2 there is unchanged within 1%
names the deposited data that would give the first bound on the mark's decay with the writer catalytically inhibited, for one download
a kinetic series on this mark exists and is now analysed, and it is NOT the quantity that entry bounds: it measures the menin inhibitor's REDISTRIBUTION kinetics in within-sample shares that are blind to uniform loss, not the mark's decay constant, which remains never-measured
three timepoints on an absolute scale is the closest this corpus has come to a decay rate, and it is still not a half-life
three timepoints on an external ruler, but the first is already past 85% loss so the fast phase is invisible
SURVIVES: DOT1L-inhibitor compound names x washout/decay return 4 records, all drug pharmacokinetics
the unmeasured constant behind the chain's H3K79me2 arrow
bounds the data field h3k79me2_decay_halflife recorded as unreported
- supports →Pinometostat (EPZ-5676) — the DOT1L inhibitor, and the most instructive failure in this field
if the mark's half-life exceeds the exposure achieved, the phase 1 tested the schedule not the mechanism
- supports →Reversibility and kinetics — does the program collapse when the fusion is removed, and how fast?
turns that entry's unreported-half-life data field into a dated, controlled absence
bounds that entry's unmeasured_number with a dated, controlled query
the literature bound for the experiment that would produce the number
- depends on →Nobody has convincingly found the H3K79 eraser - and that constraint sets the clock on every DOT1L inhibitor
no eraser is why the constant is a dilution rate rather than a turnover rate