The panobinostat H2Bub result is SEM and KOPN8 against a REH comparator: three human lines, two KMT2A partners, one non-KMT2A control
also called GSE78234 provenance · LBH589 MLL-rearranged lines · panobinostat cell lines
An entry on the drug panobinostat notes that the paper does not name which KMT2A fusions or cell lines it used. The deposited data names them: SEM and KOPN8, two human infant-leukaemia lines with different KMT2A partners, compared against REH, a leukaemia line with no KMT2A rearrangement at all.
The same thing, for a scientist
`mechanism-panobinostat-depletes-h2bub-mll-r-all` carries the caveat *"the specific KMT2A fusions and lines are not named in the abstract"* [E1]. GEO series **GSE78234** answers it and adds the control arm the caveat could not know about. Thirty-two *Homo sapiens* samples, source names given per sample: **SEM cell line with the t(4;11)**, **KOPN8 cell line with the t(11;19)** and **REH cell line with the t(12;21)**, each under `treatment: Control` or `treatment: LBH589` across four replicates, with panobinostat at 5 nM for 24 h in the shared protocol [E2]. So the study is human throughout; it contains the index fusion (SEM, KMT2A::AFF1); it contains a second KMT2A partner (KOPN8, KMT2A::MLLT1); and critically it contains a **non-KMT2A leukaemia comparator** (REH, ETV6::RUNX1), which is exactly what the MED23 deposition lacks [E3]. The 5 nM, 24 h exposure is the single most consequential number recovered here, because the graph's entry discusses H2Bub depletion without a concentration.
What the deposition adds that the abstract could not
| Sample source string | Fusion | n | Arms |
|---|---|---|---|
| SEM cell line with the t(4;11) | KMT2A::AFF1 | ~8 | Control / LBH589, 4 replicates |
| KOPN8 cell line with the t(11;19) | KMT2A::MLLT1 | ~8 | Control / LBH589, 4 replicates |
| REH cell line with the t(12;21) | ETV6::RUNX1 (non-KMT2A) | ~8 | Control / LBH589, 4 replicates |
Sixteen control and sixteen LBH589 samples in total. The shared treatment protocol reads "Panobinostat (LBH589, 5nM) or control, for 24h" and the growth protocol "leukemia cells were cultured in RPMI-1640" 2.
Three things the graph gains. A named index-fusion arm. A second-partner arm that lets partner-specific effects be separated from KMT2A-generic ones. And a non-KMT2A comparator, which converts a description into a selectivity claim - or refutes one.
The dose is the part that should change an entry
5 nM for 24 hours is a low, short exposure for an HDAC inhibitor and sits well below the concentrations at which panobinostat's pleiotropic effects are usually reported. An entry that says panobinostat depletes H2Bub in MLL-rearranged ALL without that number invites the reader to imagine a robust pharmacological effect; the deposition says the transcriptional profiling was done under a deliberately restrained condition. That is a strength for specificity and a weakness for magnitude, and the entry should say which.
| script | none - GEO accession-display text endpoint |
|---|---|
| status | run |
| result summary | 32 of 32 deposited samples are human: SEM t(4;11), KOPN8 t(11;19) and REH t(12;21), 16 control and 16 LBH589, panobinostat 5 nM for 24 h. The index fusion is present and a non-KMT2A comparator is present. The in vivo arm is not deposited. |
inputs
[ "PMID 28690313", "GSE78234" ]
counts — the numbers behind the chart
{
"samples_total": 32,
"samples_human": 32,
"samples_mouse": 0,
"cell_lines": 3,
"kmt2a_partners_represented": 2,
"non_kmt2a_comparator_lines": 1,
"panobinostat_nM": 5,
"exposure_hours": 24
}entries affected
[ "mechanism-panobinostat-depletes-h2bub-mll-r-all" ]
import axes
[ "lineage: the KOPN8 and REH arms are B-lymphoid like the index disease; no import on fusion or species for the SEM arm" ]
- Panobinostat is a pan-HDAC inhibitor with dose-limiting thrombocytopenia and cardiac toxicity, so an H2Bub-directed rationale built on a 5 nM in vitro exposure has to survive the gap to a tolerated human exposure before it means anything clinically.
- If H2Bub depletion is equally strong in the REH comparator, the mechanism is not KMT2A-selective and any therapeutic-window argument from this study collapses; the deposition contains the arm that would show this and the graph has never read it.
- The undeposited in vivo arm is where the paper's clinical claim lives, so an entry that now cites well-resolved in vitro provenance can create a false impression of having verified the result that actually matters.
- Does H2Bub depletion under 5 nM panobinostat differ between the SEM and KOPN8 arms? A partner-specific difference would be the first in this graph measured at equal dose in the same experiment.
- The paper's in vivo xenograft result is undeposited. Which fusion did the xenograft carry, and was it the same SEM and KOPN8 pair or primary infant material?
- E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper
The panobinostat paper reports in vivo anti-leukaemic activity of LBH589 against MLL-rearranged acute lymphoblastic leukaemia, and its abstract does not name the specific KMT2A fusions or cell lines used.
The HDAC inhibitor panobinostat (LBH589) exerts in vivo anti-leukaemic activity against MLL-rearranged acute lymphoblastic leukaemia and involves the RNF20/RNF40/WAC-H2B ubiquitination axis. · Garrido Castro P, van Roon EHJ, Pinhanços SS, Trentin L, Schneider P, Kerstjens M, Te Kronnie G, Heidenreich O, Pieters R, Stam RW · Leukemia 2018What this evidence cannot show
Identifiers taken from the NCBI esummary record fetched on 2026-09-19. The full text could not be read: this article has no PMCID in either the PubMed esummary or the Europe PMC core record, so the deposition is the only per-sample source available and this entry asserts nothing about the paper's Methods.
Evidence that argues against this (1)
- HDAC inhibitors have long been shown to kill t(4;11) and other ALL lines through broadly apoptotic mechanisms that are not specific to H2B ubiquitination, so attributing the drug's effect to an H2Bub axis requires more than a transcriptional profile. Romanski A et al. 2004
- E2established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.dataset
GEO series GSE78234 contains 32 Homo sapiens samples whose per-sample source names identify three lines - SEM with the t(4;11), KOPN8 with the t(11;19) and REH with the t(12;21) - each with 16 control and 16 LBH589 samples in four replicates, under a shared protocol of panobinostat 5 nM for 24 h.
The HDAC inhibitor Panobinostat (LBH589) exerts in vivo anti-leukaemic activity against infant MLL-rearranged acute lymphoblastic leukaemia (GSE78234) · GEO submitters · NCBI Gene Expression Omnibus 2018What this evidence cannot show
Read on 2026-09-19 from the GEO accession-display text endpoint. Submitter-entered. The series records the fusion only as a karyotype in a free-text source-name string, not as a structured genotype field, so KMT2A::AFF1 and KMT2A::MLLT1 are this entry's reading of t(4;11) and t(11;19) in these named lines rather than a submitter assertion. The in vivo arm named in the paper's title is not represented in the deposition.
Evidence that argues against this (1)
- The deposition covers only the transcriptional arm; the paper's headline is an in vivo xenograft result that leaves no GEO trace, so a reader who takes the deposition as the study's scope will under-read it in exactly the direction this beat warns about elsewhere. Rogic S et al. 2026
- E3strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.dataset
REH carries ETV6::RUNX1 from t(12;21) and no KMT2A rearrangement, so its presence in GSE78234 supplies a non-KMT2A leukaemia comparator arm for the panobinostat response.
The HDAC inhibitor Panobinostat (LBH589) exerts in vivo anti-leukaemic activity against infant MLL-rearranged acute lymphoblastic leukaemia (GSE78234) · GEO submitters · NCBI Gene Expression Omnibus 2018What this evidence cannot show
The t(12;21) identification is the submitter's own source-name string; its interpretation as ETV6::RUNX1 is standard but is this entry's inference, not a field in the record. A single comparator line cannot establish selectivity on its own - it establishes that a comparison was possible, which is more than most depositions in this beat offer.
Evidence that argues against this (1)
- One non-KMT2A line is a weak comparator: ETV6::RUNX1 disease differs from KMT2A-rearranged disease in far more than the fusion, so a differential response between REH and SEM confounds fusion with the entire biological background. Dietsche L et al. 2024
names the three lines and the 5 nM / 24 h exposure the abstract omitted
- related to →KMT2A::AFF1 (MLL-AF4), t(4;11)(q21;q23)
the SEM arm is the index fusion
both depositions resolve an unstated system to a human SEM-containing panel
resolved source in the unstated-system worklist