A caveat that weakened the index fusion, wrongly: the MLL-AF4 spreading deposition is 30 SEM samples plus six other lines, all human
also called GSE83671 provenance · MLL-AF4 spreading cell lines · t(4;11) H3K79 breadth
Two entries hedge the strongest human t(4;11) evidence in this graph with the note that the paper does not name its cell lines. It deposited fifty-nine human samples and they are named in detail - thirty of them are SEM, the infant pro-B line carrying exactly the fusion this project studies.
The same thing, for a scientist
`ana-index-fusion-h3k79-evidence-that-exists` and `mechanism-kmt2a-aff1-dot1l-recruitment-route` both carry the caveat *"the abstract does not name the cell lines, so the breadth of the t(4;11) evidence is not bounded by this citation"* [E1]. GEO series **GSE83671** bounds it precisely. Fifty-nine samples, **all *Homo sapiens***; the submitters annotate cell type at a granularity the abstract never reaches - 38 samples carry `cell type: Paediatric pro B-cell line derived from ALL with t(4;11)(q21;q23) translocation` and 30 carry `cell line: Leukemia cell line; SEM` [E2]. The remaining lines are named with their karyotypes: ML-2 t(6;11), THP-1 t(9;11), KOPN-8 t(11;19), MV4-11 t(4;11), CCRF-CEM t(5;14) and RCH-ACV t(1;19), plus a presentation-ALL patient sample engrafted in mice, cord-blood mononuclear cells and second-trimester fetal bone-marrow mononuclear cells [E2]. **This resolution runs the opposite way to almost every other in this beat**: the unstated system turns out to be the index fusion, in a human paediatric B-lymphoid line, with a DOT1L-inhibitor dose series (DMSO, 0.5, 1 and 2 uM EPZ-5676 for 7 days) and MLL1 and AF4 ChIP [E3]. The caveat was costing the graph confidence it had already earned.
The deposited roster, in the submitters' own words
| Cell line | Submitter's cell-type string | n |
|---|---|---|
| SEM | Paediatric pro B-cell line derived from ALL with t(4;11)(q21;q23) translocation | 30 |
| ML-2 | Adult monocytic cell line derived from AML M4 with t(6;11)(q27;q23) translocation | 4 |
| THP-1 | Paediatric monocytic cell line derived from AML M5 with t(9;11)(p21;q23) translocation | 2 |
| KOPN-8 | Infant pre B-cell line derived from ALL with t(11;19)(q23;p13) translocation | 2 |
| MV4-11 | Paediatric monocytic cell line derived from AML M5 with t(4;11)(q21;q23) translocation | 2 |
| CCRF-CEM | Paediatric immature T-cell line derived from ALL with t(5;14)(q35.1;q32.2) | 2 |
| RCH-ACV | Paediatric pre B-cell line derived from cALL with t(1;19)(q23;p13) translocation | 2 |
| PDX | Presentation ALL patient sample engrafted in mice and harvested from spleen | 3 |
| Cord blood | Mononuclear cells from full-term cord blood | 2 |
| Fetal BM | Mononuclear cells from second trimester human fetal bone marrow | 2 |
Note what else this buys the graph: the deposition contains primary normal human fetal and cord-blood comparators, which is the correct control tissue for an infant disease and is the kind of arm this project repeatedly finds missing 2.
The correction owed to two entries
Both entries should drop the clause "so the breadth of the t(4;11) evidence is not bounded by this citation" and replace it with the bound the deposition supplies: 30 of 59 deposited samples are SEM, a human paediatric KMT2A::AFF1 pro-B line, and the series additionally spans five other KMT2A-rearranged lines with three different partners, a t(4;11) AML line, two non-KMT2A leukaemia comparators and normal human fetal and cord-blood cells.
This matters beyond bookkeeping. ana-index-fusion-h3k79-evidence-that-exists exists to answer how much H3K79 evidence does this project actually have in its own fusion? An unnecessary hedge on its best citation makes the answer look worse than it is - and the graph's central hypothesis is downstream of that answer.
| script | none - GEO accession-display text endpoint |
|---|---|
| status | run |
| result summary | 59 of 59 deposited samples are human. 30 are SEM (KMT2A::AFF1 paediatric pro-B ALL). The series additionally spans ML-2 t(6;11), THP-1 t(9;11), KOPN-8 t(11;19), MV4-11 t(4;11) AML, CCRF-CEM, RCH-ACV, a presentation-ALL PDX, cord blood and second-trimester fetal bone marrow. This unstated system is the INDEX fusion, not an import. |
inputs
[ "PMID 28076791", "GSE83671", "PMC5263239" ]
counts — the numbers behind the chart
{
"samples_total": 59,
"samples_human": 59,
"samples_mouse": 0,
"samples_sem": 30,
"distinct_cell_lines": 7,
"kmt2a_partners_represented": 3,
"normal_human_comparator_samples": 4
}entries affected
[ "ana-index-fusion-h3k79-evidence-that-exists", "mechanism-kmt2a-aff1-dot1l-recruitment-route" ]
import axes
[]
- A seven-day EPZ-5676 exposure conflates direct H3K79 loss with differentiation, so a combination scheduled from this dose series may be scheduling around a secondary effect.
- SEM dominance cuts both ways: an intervention optimised against spreading domains mapped in one long-cultured line may fail on primary infant blasts whose spreading landscape has never been measured.
- The deposition's KMT2A-rearranged lines are mostly myeloid (ML-2, THP-1, MV4-11); if a selectivity claim is built by pooling them with SEM, lineage is confounded with partner exactly as it is in the DepMap arm this project already corrected.
- How many of the 30 SEM samples underlie the DOT1L-sensitivity conclusion as opposed to the spreading map? GEO fixes the system but not the sample-to-figure mapping, and the two claims have different strength.
- The series contains fetal bone-marrow and cord-blood mononuclear cells. Were those used as the normal comparator for spreading domains, and does the comparison hold at the pro-B stage specifically rather than in bulk mononuclear cells?
- E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper
The MLL-AF4 spreading paper reports that MLL-AF4 binding sites distinct from super-enhancers govern sensitivity to DOT1L inhibition, and its abstract does not name the cell lines used.
MLL-AF4 Spreading Identifies Binding Sites that Are Distinct from Super-Enhancers and that Govern Sensitivity to DOT1L Inhibition in Leukemia. · Kerry J, Godfrey L, Repapi E, Tapia M, Blackledge NP, Ma H, Ballabio E, O'Byrne S, Ponthan F, Heidenreich O, Roy A, Roberts I, Konopleva M, Klose RJ, Geng H, Milne TA · Cell Rep 2017What this evidence cannot show
Identifiers taken from the NCBI esummary record fetched on 2026-09-19. Full text was read from Europe PMC PMC5263239 (open access); it names MLL-AF4 184 times and SEM 36 times, consistent with the deposition. The claim here is about the abstract, which is where the graph's caveat was anchored.
Evidence that argues against this (1)
- A SEM-dominated deposition is not automatically representative of t(4;11) disease: SEM is a relapse-derived line adapted to culture for decades, and the same laboratory's own PDX and primary arms are a small minority of the samples, so line-level findings still need patient-level confirmation. Greil J et al. 1994
- E2established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.dataset
GEO series GSE83671 contains 59 Homo sapiens samples annotated by cell line and karyotype, of which 30 are SEM and 38 carry the cell-type string 'Paediatric pro B-cell line derived from ALL with t(4;11)(q21;q23) translocation', alongside ML-2, THP-1, KOPN-8, MV4-11, CCRF-CEM and RCH-ACV, a presentation-ALL xenograft, cord-blood and second-trimester fetal bone-marrow mononuclear cells.
MLL-AF4 Spreading Identifies Binding Sites that Are Distinct from Super-Enhancers and that Govern Sensitivity to DOT1L Inhibition in Leukemia (GSE83671) · GEO submitters · NCBI Gene Expression Omnibus 2017What this evidence cannot show
Read on 2026-09-19 from the GEO accession-display text endpoint and tallied by characteristic string. Submitter-entered. The counts of the cell-type and cell-line strings differ (38 versus 30) because some samples carry one field and not the other, so 30 is the conservative SEM count and 38 the count of samples the submitters describe as the t(4;11) pro-B line. Sample-to-figure mapping is not recoverable from GEO.
Evidence that argues against this (1)
- Cell-line strings in GEO are submitter-entered and uncurated across depositions generally, so even an unusually well-annotated series like this one records what the submitters believe their cells to be rather than an authenticated identity. Rogic S et al. 2026
- E3established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.dataset
The deposition includes an EPZ-5676 dose series (DMSO, 0.5, 1 and 2 uM for 7 days, three samples each) and ChIP for MLL1 (Bethyl A300-086A, 7 samples), AF4 (Abcam ab31812, 3 samples) and H3K36me3, together with nascent-RNA samples.
MLL-AF4 Spreading Identifies Binding Sites that Are Distinct from Super-Enhancers and that Govern Sensitivity to DOT1L Inhibition in Leukemia (GSE83671) · GEO submitters · NCBI Gene Expression Omnibus 2017What this evidence cannot show
Treatment and antibody characteristics read on 2026-09-19. A seven-day EPZ-5676 exposure is long enough that secondary and differentiation effects are inseparable from direct H3K79 loss; the deposition contains no short-exposure arm. The antibody lots are not recorded for every sample.
Evidence that argues against this (1)
- DOT1L inhibition in KMT2A-rearranged cells acts partly through enhancer-promoter contacts at loci such as PROM1/CD133 rather than solely through fusion-bound spreading domains, so a spreading-centric reading of the dose series may attribute to the fusion what belongs to genome-wide H3K79 loss. Godfrey L et al. 2021
bounds the t(4;11) evidence the entry hedged: 30 of 59 deposited samples are SEM
removes an unnecessary hedge on this entry's human t(4;11) citation
- related to →KMT2A::AFF1 (MLL-AF4), t(4;11)(q21;q23)
this unstated system resolves to the index fusion rather than an import
the deposition carries an EPZ-5676 dose series in SEM
both depositions resolve an unstated system to a human SEM-containing panel
resolved source in the unstated-system worklist