Oncofusion

start / graph / absence-no-cell-state-for-aff4

Analysisstrong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.Q60-cellstate2

AFF4 has never been placed in a haematopoietic cell state — every SEC cell-state result is in another tissue

also called AFF4 bounded cell-state absence · SEC scaffold absence

AFF4 is the scaffold of the elongation complex this disease runs through, and nobody has shown what cell condition it maintains in blood. The results that do exist are in brain tumours, bladder cancer and skin.

The same thing, for a scientist

Bounded query on 2026-09-20: `(AFF4 OR AF5q31 OR MCEF)[tiab] AND <18-term cell-state clause> AND <leukaemia clause>` returns **1**, which does not survive a title check [E1]. Unscoped, the same gene-plus-state query returns 5, and all five are non-haematopoietic: epidermal progenitors, bladder cancer stem cells, a paused-Pol-II quiescence programme, diffuse midline glioma, and a 2026 elongation-complex structure paper. Per rule 64 the complex form was run — `("super elongation complex" OR "superelongation complex")[tiab] AND <state clause>` returns 10 — and its state results are in neural stem cells and diffuse midline glioma, not in blood [E1]. DepMap adds nothing: AFF4 is dispensable in 99.6% of 1,258 lines and in every KMT2A-rearranged line [E2].

Go deeper
Why this absence is more surprising than the others

AFF4 is the SEC scaffold. This graph's account of KMT2A-fusion transcription runs through the super elongation complex, and AFF4 is named in that account repeatedly. Yet the gene has no requirement anywhere in a 1,258-line screen and no cell-state characterisation in haematopoiesis at all.

Two readings, and the graph should not pick between them without evidence. Either the SEC's role in this disease is carried by AFF1 with AFF4 redundant — which the DepMap contrast between AFF1 (-0.257 in KMT2A-r) and AFF4 (+0.024) mildly supports — or the ALF family buffers itself so completely that no single-gene experiment can see it. The second would also explain the AFF1 null.

Rule 64 was run and did not rescue it

Brief rule 64 requires the complex form before a subunit absence is written, because a paper may frame everything at complex level and never name a subunit. That was done. The complex form returns ten records and its cell-state members are PMID 28350987 (The Super Elongation Complex Drives Neural Stem Cell Fate Commitment) and PMID 32268092 (Super Elongation Complex as a Targetable Dependency in Diffuse Midline Glioma) 13.

The founding leukaemia SEC paper (PMID 20159561, AFF4, a component of the ELL/P-TEFb elongation complex and a shared subunit of MLL chimeras, can link transcription elongation to leukemia) was opened per rule 80 — PMC2872029, 52,184 characters — and contains zero occurrences of any of the eighteen cell-state terms 4. The absence held through both checks.

Facts and figures
genegene-aff4
symbolAFF4
uniprotQ9UHB7
statusrun
query(AFF4[tiab] OR "AF5q31"[tiab] OR "MCEF"[tiab]) AND <cell-state clause> AND <leukaemia clause>
count1
on topic after title check0
on topic after opening full texts0
gene clause alone control151
unscoped count5
complex form query("super elongation complex"[tiab] OR "superelongation complex"[tiab]) AND <cell-state clause>
complex form count10
result summaryAFF4 has no haematopoietic cell-state characterisation and no requirement in any screened line. Rule 64 complex form and rule 80 full text both run; the absence held.
state clause alone control96743
date2026-09-20
toolNCBI esearch db=pubmed
absence classmeasured-not-analysed
absence class basisARCHIVE CHECK RUN 2026-09-21 (king), which is what moved this off unclassified-not-checked. GEO holds 760 human bone-marrow single-cell RNA-seq DataSets (query: "Homo sapiens"[Organism] AND "bone marrow"[All Fields] AND ("single cell" OR "scRNA-seq")[All Fields] AND "expression profiling by high throughput sequencing"[DataSet Type]; translation recorded, ran clean). GSE120221 was verified individually: 25 samples, Homo sapiens, human bone marrow by scRNA-seq with matched mass and flow cytometry. WHAT THAT DATA CAN SETTLE: which haematopoietic populations express AFF4 and whether its expression tracks a state such as HSC quiescence versus cycling - the associative placement this entry's own literature queries were looking for. WHAT IT CANNOT: function. A functional placement needs perturbation in the state, and that remains never-measured. So the entry is split - the descriptive half is a desk job on deposited data, the functional half still needs an experiment.
absence class assigned2026-09-21 (cycle 47, king)
full texts opened
[
  "20159561 (PMC2872029, 52,184 chars) - zero state-term occurrences"
]
cell state clause terms
[
  "quiescence",
  "quiescent",
  "dormancy",
  "dormant",
  "drug-tolerant",
  "drug tolerant",
  "persister",
  "persisters",
  "leukemia stem cell",
  "leukemia stem cells",
  "leukaemia stem cell",
  "leukaemia stem cells",
  "self-renewal",
  "self renewal",
  "differentiation block",
  "differentiation arrest",
  "minimal residual disease",
  "measurable residual disease"
]
archive checked
{
  "archive": "GEO DataSets",
  "date": "2026-09-21",
  "datasets_matching": 760,
  "verified_example": "GSE120221 (25 samples, Homo sapiens, human bone marrow scRNA-seq)",
  "closes_the_descriptive_half": true,
  "closes_the_functional_half": false
}
How this could bite us back
  • An intervention aimed at the SEC through AFF4 has no genetic support in this disease at all - the gene is dispensable in every line screened.
  • If ALF-family redundancy is the reason, then any single-agent SEC intervention will be buffered the same way.
Still open
  1. Is AFF4 functionally redundant with AFF1 in KMT2A-rearranged cells? A double knockout has not been reported in this disease.
  2. Does the SEC cell-state biology found in neural stem cells and glioma transfer to haematopoiesis, or is the complex doing something different there?
Every source behind this entry (4)
  1. E1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database

    A bounded PubMed query pairing AFF4 and its aliases with an eighteen-term cell-state clause and a leukaemia clause returns 1 record, which fails a title check; the unscoped gene-plus-state query returns 5, all non-haematopoietic, and the complex form returns 10 whose state results are in neural stem cells and glioma.

    NCBI PubMed E-utilities esearch, db=pubmed, queried 2026-09-20 · NCBI Entrez Programming Utilities 2026
    What this evidence cannot show

    Bounded by titles and abstracts. Counts as of 2026-09-20. The complex-form query uses the ordinary-word-contaminated phrase 'super elongation complex', which was quoted to avoid the synonym explosion rule 69 describes.

    Evidence that argues against this (1)
    • The absence is bounded by the HAEMATOPOIETIC literature only. The super elongation complex demonstrably does maintain a cell state elsewhere - it drives neural stem cell fate commitment and is a targetable dependency in diffuse midline glioma - so 'AFF4 has no cell-state function' would be false; only 'no haematopoietic cell-state function has been shown' survives. Dahl NA et al. 2020
  2. E2strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database

    In DepMap fetched 2026-09-20, AFF4 is depleted below -0.5 in 0.4% of 1,258 screened lines (mean -0.056) and its mean across eleven KMT2A-rearranged lines is +0.024.

    What this evidence cannot show

    Whole-gene CRISPR; AFF4 is not a fusion partner in these lines so the allele confound that applies to AFF1 does not apply here, which makes this null cleaner than AFF1's. Cancer lines in culture.

    Evidence that argues against this (1)
    • PUBLISHED CONFLICTING RESULT against reading the near-zero gene effect as 'AFF4 is not required'. Luo et al. showed that MYC is a direct target of AFF4/SEC, that SEC recruitment to the MYC gene regulates MYC expression in acute myeloid AND lymphoid leukaemia cells, and concluded that AFF4/SEC could be a therapeutic target in leukaemia and other MYC-overexpressing cancers. The same paper supplies the reconciliation and it is not a caveat about culture: they biochemically isolated SEC-L2 and SEC-L3, containing AFF2 and AFF3 with the same P-TEFb, ENL/MLLT1 and AF9/MLLT3 partners. A whole-gene AFF4 knockout in a cell that retains three other AFF-containing elongation complexes is a redundancy measurement, and the claim in this item that the null is 'cleaner than AFF1's' because no allele confound applies is therefore only half the story. Luo Z et al. 2012
  3. E3moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper

    The super elongation complex is a targetable dependency in diffuse midline glioma.

    PMID 32268092DOI
    What this evidence cannot show

    A non-haematopoietic tumour. Cited here to show where SEC cell-state work actually lives, not as evidence about leukaemia. Abstract read in this beat.

    Evidence that argues against this (1)
    • PUBLISHED CONFLICTING RESULT about which family member carries the function, which is prior to asking which tissue it is studied in. Melko et al. showed that AFF2/FMR2, AFF3/LAF4 and AFF4/AF5q31 all localise to nuclear speckles, all bind RNA with high apparent affinity for G-quadruplex structures, and all modulate splicing of the same mini-gene in vivo; they propose functional redundancy among AFF family members and invoke it to explain the mild FRAXE phenotype when AFF2 is silenced. A demonstration that 'the SEC' is a targetable dependency in diffuse midline glioma therefore does not localise the dependency to AFF4, and neither does its absence in blood localise an absence to AFF4. Melko M et al. 2011
  4. E4strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

    The founding paper establishing AFF4 as a component of the ELL/P-TEFb complex and a shared subunit of MLL chimeras contains no occurrence of any of the eighteen cell-state terms used in this beat.

    PMID 20159561DOI
    What this evidence cannot show

    Full text read via PMC2872029 on 2026-09-20, 52,184 characters after tag stripping. A term-absence in one paper is weaker evidence than a term-presence would be, and the paper predates most cell-state vocabulary in this field.

    Evidence that argues against this (1)
    • PUBLISHED CONFLICTING RESULT on what the term-absence bounds. The founding AFF4 paper is from 2010 and the cell-state-relevant content of AFF4 biology was published two years later under none of the eighteen terms: Luo et al. report that of the three SEC-family complexes only SEC is required for proper induction of HSP70 upon STRESS, that SEC-L2 and SEC-L3 control different gene subsets, and that AFF4/SEC plays the dominant role in rapid transcriptional induction. Stress response and inducibility are cell-state properties described entirely in elongation-factor vocabulary. The absence recorded here is an absence in one vocabulary, and the caveat says a term-absence is weak evidence without saying which words would have found it. Luo Z et al. 2012
Connected to