Oncofusion

start / graph / ana-unstated-system-ccnd3-cdk46-lines-unresolved

Analysisestablished confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.Q18b-unstated-systems

Bounded failure: the CDK4/6 cell lines behind two therapeutic entries are unrecoverable although the article is marked free access

also called PMID 30381403 bounded failure · CCND3 CDK4/6 cell lines · PMC6234363 empty body

Two entries recommending CDK4/6 inhibitors in KMT2A-rearranged leukaemia rest on a paper that never names the cell lines it tested them in. The article is tagged as free to read, but both ways of fetching its text return only the title page, and it deposited nothing.

The same thing, for a scientist

`gene-ccnd3` hedges PMID 30381403 with *"The cell lines used for the CDK4/6 inhibitor experiments are not named in the abstract"*, and `target-cdk4-6-inhibition-kmt2a-r` with *"The cell lines are not named in the abstract and no IC50 or in vivo data were read"* [E1]. Neither resolved. The article carries PMCID **PMC6234363** with the custom-meta field `access: free`, and Europe PMC reports `inEPMC: Y`. Despite that, `fullTextXML` returns **HTTP 500** and `efetch db=pmc` returns **18,700 characters of front matter with no `<body>` element** - the same signature documented in `ana-unstated-system-menin-n-terminus-unresolved`, and notable here because the `access: free` tag makes it look more readable than the others [E2]. No deposition exists: elink to GEO returns zero, and a GEO keyword search on `CCND3 AND leukemia` returns eight series, none of which belongs to this study [E3]. **This is the bounded failure with the most direct therapeutic consequence in the beat.** `target-cdk4-6-inhibition-kmt2a-r` is a target entry; CDK4/6 inhibitors are approved agents with known pharmacology; and the question that cannot be answered is *in which leukaemia cells did anyone actually see this work* - which is the first question anyone would ask before opening a trial.

Go deeper
What a therapeutic entry is missing without the cell lines

Three things, each of which changes a development decision:

  • Lineage. The paper's title says MLL-rearranged acute myeloid leukemia. If the CDK4/6 experiments were done in AML lines, then a B-ALL recommendation is a lineage import that neither entry currently flags.
  • Fusion. CCND3 mutations are reported in KMT2A-rearranged AML; whether the inhibitor experiments used a KMT2A::AFF1 line, a KMT2A::MLLT3 line, or a CCND3-mutant line of any genotype is undetermined.
  • Whether the sensitivity tracks the mutation or the rearrangement. A CCND3-mutant line and a KMT2A-rearranged line are different claims, and an entry recommending CDK4/6 inhibition for KMT2A-rearranged disease needs the second.

None of these is recoverable. The entries' existing caveat - no IC50 or in vivo data were read - is correct and now has a reason attached.

The pattern across this beat's four unrecoverable PMC records

Four papers returned a PMCID and no body: PMC7566887 (2007), PMC3593849 (2013), PMC6234363 (2018) and PMC3795288 (2013). They span eleven years and four publishers, and one of them is tagged access: free. So the failure does not track age, journal or the access flag, which means it cannot be predicted and must be tested per paper.

Against that, five papers returning the identical Europe PMC HTTP 500 were fully recoverable through efetch db=pmc. The practical consequence for any future beat: a Europe PMC 500 costs one extra request to resolve, and the answer is about even money.

Facts and figures
scriptnone - Europe PMC, NCBI efetch db=pmc, elink and GEO keyword search
statusrun
result summaryUnresolved. PMCID exists and is tagged access: free, but Europe PMC fullTextXML returns HTTP 500 and NCBI efetch db=pmc returns no body element. No deposition. Two therapeutic entries retain an unnamed cell-line panel.
what would resolve itFetching the article from the Blood Advances site directly, which is open access; or a publisher deposit of full text to PMC. This is the cheapest unresolved item in the beat for a reader with a browser.
resolution classbounded failure
inputs
[
  "PMID 30381403",
  "PMC6234363"
]
routes tried
[
  "PubMed esummary (pmc: PMC6234363)",
  "Europe PMC core (inEPMC Y, isOpenAccess N)",
  "Europe PMC fullTextXML (HTTP 500, twice)",
  "NCBI efetch db=pmc (18,700 chars, no <body>, access: free tag present)",
  "elink pubmed->gds, sra, biosample, bioproject (0 each)",
  "esearch db=gds 'CCND3 AND leukemia' (8 series, all unrelated by title)"
]
entries affected
[
  "gene-ccnd3",
  "target-cdk4-6-inhibition-kmt2a-r"
]
How this could bite us back
  • Recommending an approved CDK4/6 inhibitor for KMT2A-rearranged B-ALL from an AML-titled paper whose cell lines nobody has read is the kind of recommendation that survives review precisely because it names a familiar drug.
  • CDK4/6 inhibitors cause neutropenia, which in an infant already marrow-suppressed by induction chemotherapy is a dose-limiting interaction that a cell-line IC50 would not predict and that this graph cannot bound from an unread paper.
  • If the sensitivity tracks CCND3 mutation rather than rearrangement, then the eligible population is a small subset of KMT2A-rearranged AML and essentially none of infant KMT2A::AFF1 ALL, and the target entry currently implies otherwise.
Still open
  1. In which cell lines was CDK4/6 inhibition tested, and were they AML or B-ALL? A target entry recommending an approved drug class should not be unable to answer this.
  2. Does CDK4/6 sensitivity track the CCND3 mutation or the KMT2A rearrangement? The two entries currently assume the latter and the paper's title says AML.
Every source behind this entry (3)
  1. E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper

    The CCND3 paper reports recurrent CCND3 mutations in MLL-rearranged acute myeloid leukaemia, and its abstract does not name the cell lines used for the CDK4/6 inhibitor experiments.

    Recurrent CCND3 mutations in MLL-rearranged acute myeloid leukemia. · Matsuo H, Yoshida K, Fukumura K, Nakatani K, Noguchi Y, Takasaki S, Noura M, Shiozawa Y, Shiraishi Y, Chiba K, Tanaka H, Okada A, Nannya Y, Takeda J, Ueno H, Shiba N, Yamato G, Handa H, Ono Y, Hiramoto N, Ishikawa T, Usuki K, Ishiyama K, Miyawaki S, Itonaga H, Miyazaki Y, Kawamura M, Yamaguchi H, Kiyokawa N, Tomizawa D, Taga T, Tawa A, Hayashi Y, Mano H, Miyano S, Kamikubo Y, Ogawa S, Adachi S · Blood Adv 2018
    PMID 30381403DOI
    What this evidence cannot show

    Identifiers taken from the NCBI esummary record fetched on 2026-09-19. This entry asserts nothing about the paper's experiments and does not guess the lines. The paper's own title specifies acute myeloid leukaemia, which is the only lineage information available.

    Evidence that argues against this (1)
    • Cyclin D3 and CDK4/6 dependency in B-cell precursor ALL has its own literature independent of KMT2A rearrangement, so a CDK4/6 recommendation for B-lineage disease need not rest on this paper at all - and the graph would be better served by a B-ALL citation than by an unreadable AML one. Dietsche L et al. 2024
  2. E2established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database

    PMC6234363 returns HTTP 500 from Europe PMC fullTextXML and 18,700 characters of front matter with no body element from NCBI efetch db=pmc, despite carrying the custom-meta field 'access: free' and Europe PMC reporting inEPMC Y.

    Europe PMC fullTextXML and NCBI efetch db=pmc responses for PMC6234363 · Europe PMC and NCBI Entrez Programming Utilities 2026
    What this evidence cannot show

    Run on 2026-09-19 from a single network location, with the Europe PMC request repeated after clearing a cached error to ensure a genuine retry. The 'access: free' tag describes the article's licence status at the publisher, not the presence of text in PMC, and the two are evidently independent. A later publisher deposit could change this.

    Evidence that argues against this (1)
    • Blood Advances is an open-access journal and the article is almost certainly readable at the publisher's own site, so this is a failure of the programmatic route rather than of access - a browser would very likely succeed where these endpoints did not. Rogic S et al. 2026
  3. E3strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database

    No deposition corresponds to this paper: elink from the PMID to GEO, SRA, BioSample and BioProject returns zero records, and a GEO keyword search on 'CCND3 AND leukemia' returns eight series, none of which belongs to this study.

    What this evidence cannot show

    Run on 2026-09-19. The eight keyword hits were checked by title and cover Ph-like B-ALL BRG1 inhibition, MZ1 in B-ALL subtypes, a miR-497~195 cluster study, uveal melanoma, cyclophosphamide in PBMCs, TLX networks and mouse T-cell lymphomas - none is this paper. A mutation-discovery study may have deposited exome or targeted sequencing to dbGaP under controlled access, which this route does not see and which would not name cell lines in any case.

    Evidence that argues against this (1)
    • Six of sixteen resolutions in this beat came from accessions printed in a data-availability statement rather than from elink, so for a paper whose full text is unreachable the most productive discovery route is itself unavailable and the deposition negative is correspondingly weak. Neville D et al. 2026
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