Oncofusion

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Explainerstrong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.Q29-mllt3-yeats-loss

THP-1 (CVCL_0006): the default KMT2A::MLLT3 line, from a one-year-old, carrying NRAS G12D and a TP53 frameshift

also called THP-1 · THP1 · CVCL_0006 · ACH-000146 · Tohoku Hospital Pediatrics-1

THP-1 is the cell line most papers reach for when they want this fusion, and almost nobody notices it came from a one-year-old boy. It also carries two other cancer mutations that can drive the same phenotypes the fusion is usually credited with.

The same thing, for a scientist

Cellosaurus CVCL_0006, fetched by accession on 2026-09-20 with the primary name read back: THP-1, male, **1 year old**, `NCIt C9163 childhood acute monocytic leukemia`, derived in situ from peripheral blood, carrying the gene fusion `KMT2A + MLLT3` (names KMT2A-MLLT3, MLL-MLLT3, MLL-AF9), **NRAS p.Gly12Asp heterozygous** and **TP53 p.Arg174fs*3 heterozygous**, plus a CSNK2A1-DDX39B fusion; DepMap ACH-000146, ATCC TIB-202, DSMZ ACC-16, and a member of the DepMap/CCLE, COSMIC, Human Protein Atlas Cell Atlas, LL-100, MD Anderson and ATCC RAS panels [E1]. The founding report is the 1980 establishment paper, whose title names it an acute monocytic leukaemia line [E2]; the MLL-AF9 translocation was characterised cytogenetically and molecularly in 2000 [E3]. Two facts about it are routinely dropped in the literature that uses it. **It is a paediatric line** - the name is an abbreviation of Tohoku Hospital Pediatrics-1 - which matters because this graph's `concept-the-eleven-lines-are-nine-patients` records that the DepMap KMT2A-rearranged panel contains no patient under one year and is mostly adult. And **it is NRAS-mutant and TP53-frameshifted**, so proliferation, apoptotic priming and differentiation phenotypes measured in it have two competing drivers that an isogenic control would separate and that a single-line experiment does not.

Go deeper
The record, as read back
fieldvalue
accessionCVCL_0006 (primary name read back: THP-1)
sex / ageMale / 1Y
diseaseNCIt C9163 childhood acute monocytic leukemia; ORDO Orphanet_514
sitein situ, peripheral blood (UBERON_0000178)
fusionKMT2A + MLLT3 (PubMed=11066077; PubMed=15843827)
co-lesionsNRAS p.Gly12Asp het; TP53 p.Arg174fs*3 het; CSNK2A1-DDX39B fusion
DepMapACH-000146
doubling time60-70 h (PubMed=6970727); 26 h (PubMed=25984343); ~35-50 h (DSMZ)

All from the Cellosaurus record fetched by accession on 2026-09-20 1.

What using THP-1 commits you to

A paediatric monocytic genotype. The line is from a one-year-old with acute monocytic leukaemia. That is an unusually good match to the paediatric-AML stratum where MLLT3 is the commonest partner (36.6% of paediatric KMT2A-r AML) and a poor match to the infant-ALL stratum that holds the partner's largest single patient group (157 cases).

A RAS-pathway driver. NRAS G12D is an activating mutation, and RAS-pathway co-mutation is a documented route to menin-inhibitor resistance in this graph's resistance-ras-flt3-wt1-comutation-menin. A menin-inhibitor or DOT1L-inhibitor sensitivity measured in THP-1 is measured in a RAS-mutant background.

A TP53 frameshift. p.Arg174fs*3 is a truncating TP53 lesion, so apoptotic priming and any p53-dependent readout in this line is not the p53-wild-type case. This graph's resistance-tp53-apoptotic-priming-menin argues that TP53 status modulates response to menin inhibition; THP-1 sits on one side of that.

The fusion architecture is not published for this line. No intron- or residue-level breakpoint is recorded for THP-1's KMT2A::MLLT3 in the Cellosaurus record, so whether its fusion protein matches the 98.4% YEATS-negative patient architecture is assumed rather than established.

Facts and figures
accessionCVCL_0006
accession verifiedfetched from https://api.cellosaurus.org/cell-line/CVCL_0006?format=txt on 2026-09-20; primary name read back as THP-1
depmap IDACH-000146
atccTIB-202
dsmzACC-16
fusionKMT2A::MLLT3 (MLL-AF9)
sexMale
age at derivation1 year
lineageacute monocytic leukaemia (FAB M5)
siteperipheral blood
fusion breakpoint publishedfalse
yeats in fusion notenot established for this line; no breakpoint is annotated, so YEATS absence is inferred from the patient distribution rather than measured
reciprocal statusunassayed
co lesions
[
  "NRAS p.Gly12Asp heterozygous",
  "TP53 p.Arg174fs*3 heterozygous",
  "CSNK2A1-DDX39B fusion"
]
panels
[
  "DepMap/CCLE",
  "COSMIC cell lines project",
  "Human Protein Atlas Cell Atlas",
  "LL-100",
  "MD Anderson Cell Lines Project",
  "ATCC RAS genetic alteration panel (TCP-1031)"
]
How this could bite us back
  • A compound prioritised on THP-1 is prioritised in an NRAS-mutant, TP53-truncated background, and both lesions are independently associated with worse response to menin inhibition in this graph's resistance entries.
  • Because THP-1's breakpoint is unpublished, an experiment designed around 'the fusion lacks YEATS' is relying on a population statistic rather than on a property of the cells in the dish.
Still open
  1. Where does THP-1's KMT2A::MLLT3 break within MLLT3? No breakpoint is annotated, so the line's YEATS status is assumed from the patient distribution.
  2. How much of THP-1's phenotype is NRAS G12D rather than the fusion? An isogenic NRAS-corrected THP-1 would separate them and does not appear in this graph's literature.
  3. Is THP-1 reciprocal-positive? Unassayed, like every line in the panel.
Every source behind this entry (3)
  1. E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database

    Cellosaurus CVCL_0006 records THP-1 as a male, 1-year-old childhood acute monocytic leukaemia line derived in situ from peripheral blood, carrying a KMT2A + MLLT3 gene fusion, NRAS p.Gly12Asp heterozygous, TP53 p.Arg174fs*3 heterozygous and a CSNK2A1-DDX39B fusion, with DepMap ACH-000146, ATCC TIB-202 and DSMZ ACC-16 and membership of the DepMap/CCLE, COSMIC, Human Protein Atlas, LL-100, MD Anderson and ATCC RAS panels.

    Cellosaurus record CVCL_0006 (THP-1) · Cellosaurus (SIB) 2026
    What this evidence cannot show

    Fetched by accession on 2026-09-20 with the primary name read back. Cellosaurus aggregates published annotation; variant calls come from the sources cited in each comment (here ATCC, Cosmic-CLP and DepMap) and have not been independently re-verified here. No breakpoint or fusion-transcript structure is annotated for this line.

    Evidence that argues against this (1)
    • Cellosaurus records the doubling time of THP-1 variously as 60-70 hours, 26 hours and ~35-50 hours from three sources, which is a reminder that a line's recorded properties drift between laboratories and that a single curated record is a summary of heterogeneous material, not a specification of the vial in anyone's freezer. Cellosaurus (SIB) 2026
  2. E2established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper

    THP-1 was established and characterised as a human acute monocytic leukaemia cell line.

    Establishment and characterization of a human acute monocytic leukemia cell line (THP-1). · Tsuchiya S, Yamabe M, Yamaguchi Y, et al. · Int J Cancer 1980
    PMID 6970727DOI
    What this evidence cannot show

    1980; the founding characterisation predates molecular fusion assignment entirely, so the KMT2A::MLLT3 status comes from later work, not from this paper.

    Evidence that argues against this (1)
    • A 1980 morphological and immunological characterisation cannot establish lineage in the terms used today, and the line's disease term in Cellosaurus (childhood acute monocytic leukemia) is a modern ontology mapping applied retrospectively. Drexler HG et al. 2004
  3. E3strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

    Cytogenetic and molecular analysis of the acute monocytic leukemia cell line THP-1 identified an MLL-AF9 translocation.

    Cytogenetic and molecular analysis of the acute monocytic leukemia cell line THP-1 with an MLL-AF9 translocation. · Odero MD, Zeleznik-Le NJ, Chinwalla V, et al. · Genes Chromosomes Cancer 2000
    PMID 11066077
    What this evidence cannot show

    Read as title and as the Cellosaurus curation citing it; the full text was not retrieved, so the intron-level junction it may report is not recorded here. No PubMed DOI is registered for this record, only a publisher pii.

    Evidence that argues against this (1)
    • Because this beat did not read the full text, THP-1's MLLT3 breakpoint position - and therefore whether its fusion protein is YEATS-negative like 98.4% of patients - remains an assumption in every experiment this graph cites that uses the line. Meyer C et al. 2023
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