Oncofusion

start / graph / target-hla-dr-class-ii-heterodimer

Targetmoderate confidence 3 of 5: One strong study, or several smaller consistent ones.Q48-surface-antigens

HLA-DR - a two-chain MHC class II heterodimer, so no single gene symbol denotes the surface marker a flow report calls HLA-DR

also called HLA-DR · MHC class II DR · Ia antigen · class II histocompatibility antigen DR

HLA-DR is the flag that immune cells use to show fragments of proteins to other immune cells, and it is made of two separate chains from two separate genes. When a flow-cytometry report says HLA-DR it means the assembled pair on the cell surface, which is why no single gene name can stand for it.

The same thing, for a scientist

HLA-DR is a **heterodimer**: an alpha chain (HLA-DRA, UniProt **P01903**, 254 aa, essentially non-polymorphic) paired with a beta chain, most commonly HLA-DRB1 (**P01911**, 266 aa, one of the most polymorphic loci in the human genome) [E1][E2]. An anti-HLA-DR flow antibody detects the assembled surface complex. **No single gene symbol denotes it**, which is why it sits in this beat alongside the glycan antigens even though both of its chains are perfectly ordinary protein-coding genes. **The blindness here has a different shape from CD15's.** CD15 has no gene at all. HLA-DR has **two**, and the graph's 15 mentions of *HLA-DR* [E5] are almost all flow-panel statements about the surface marker, while a symbol-keyed queue would look for `HLA-DRA` or `HLA-DRB1` and find a handful of immunogenetics contexts that are about transplant matching and disease association, not about the blast's phenotype. **The two vocabularies do not intersect**, and that is measurable: `"HLA-DR" AND (KMT2A OR MLL)` returns **44** PubMed records while `(HLA-DRA OR HLA-DRB1) AND (KMT2A OR MLL) AND leukemia` returns **2**, of which one is a transplant-donor paper and the other is a chromatin paper [E4]. **The one substantive mechanistic link found on this beat, and it is about the chain, not the marker.** Koues and colleagues showed that **multiple common MLL/COMPASS subunits bind the inducible MHC-II and CIITA promoters**, that overexpressing a single common MLL/COMPASS subunit significantly enhanced promoter activity and **MHC-II HLA-DRA expression**, and that those subunits are required for H3K4 trimethylation at MHC-II and CIITA promoters [E3]. **That is a direct, chain-specific, KMT2A-family link to HLA-DR expression** - and it is about wild-type MLL/COMPASS, not about a fusion, which is stated rather than elided. **Which chain does any given source mean?** Almost always: it does not say. Every clinical and flow source read on this beat reports 'HLA-DR' with no chain specified, and this entry records that as unresolved rather than assigning one.

Go deeper
Which chain a source means - a standing answer of 'unstated'

Why type: "target" and not gene-. data/graph/SCHEMA.md has no antigen node type, and there is no single gene to point at. An id gene-hla-dr would be wrong in the specific way this beat exists to correct: it asserts a one-to-one gene-to-marker mapping that does not exist. The two chains get their own gene- entries: gene-hla-dra and gene-hla-drb1.

source read on this beatwhat it sayschain resolved?
Koues 2010 3'MHC-II HLA-DRA expression'HLA-DRA, explicitly
flow-cytometry and MPAL literature surfaced by "HLA-DR" AND (KMT2A OR MLL) (44 records)'HLA-DR' on a blastunstated
this graph's 15 existing mentions 5'HLA-DR' in panel listsunstated

The rule this beat adopts and recommends: when a source says only HLA-DR, record chain: "unstated". Do not resolve it to HLA-DRA because that is the chain with a UniProt record you happened to fetch, and do not resolve it to HLA-DRB1 because that is the polymorphic one people discuss. An anti-HLA-DR antibody detects the dimer and is usually raised against a monomorphic determinant, so the measurement genuinely does not distinguish the beta chain allele - the ambiguity is in the assay, not only in the writing.

Why HLA-DR matters in this disease, briefly and with its limits

HLA-DR is part of the standard acute-leukaemia flow panel and one of the discriminators used in assigning lineage, including in mixed-phenotype acute leukaemia, where KMT2A rearrangement is enriched. It appears in 15 entries of this graph in exactly that role 5.

What this beat did not find: any source establishing that HLA-DR expression on a KMT2A-rearranged blast is fusion-driven, prognostic, or different from other B-precursor ALL. The (HLA-DRA OR HLA-DRB1) AND (KMT2A OR MLL) AND leukemia intersection is 2 records and neither is such a study 4. That is a bounded absence with controls, not a claim that HLA-DR is uninteresting.

Facts and figures
antigen classMHC class II heterodimer (alpha-beta protein complex)
encoded by a genefalse
why not a genetwo chains from two loci; HLA-DRA pairs with HLA-DRB1, DRB3, DRB4 or DRB5, and an anti-HLA-DR antibody detects the assembled dimer at a monomorphic determinant
chains
[
  {
    "gene": "HLA-DRA",
    "uniprot": "P01903",
    "length_aa": 254,
    "polymorphism": "essentially non-polymorphic"
  },
  {
    "gene": "HLA-DRB1",
    "uniprot": "P01911",
    "length_aa": 266,
    "polymorphism": "highly polymorphic; DRB3/4/5 also form DR dimers"
  }
]
chain resolution of sources
{
  "PMID 20181089": "HLA-DRA, explicit",
  "all clinical and flow sources read on this beat": "unstated"
}
graph mentions 2026 09 20
{
  "HLA-DR": 15
}
pubmed 2026 09 20
{
  "\"HLA-DR\" AND (KMT2A OR MLL)": 44,
  "(HLA-DRA OR HLA-DRB1) AND (KMT2A OR MLL) AND leukemia": 2,
  "controls": {
    "HLA-DRA OR HLA-DRB1": 12630,
    "KMT2A OR MLL": 9229
  }
}
How this could bite us back
  • **A class II immune-evasion hypothesis cuts against immunotherapy, not for it.** If KMT2A fusions reduce MHC class II at CIITA-dependent promoters, blasts would be poorer at presenting to CD4 T cells - which would matter for any T-cell-engaging therapy, including the CLEC12A programmes on this beat.
  • **Do not resolve 'HLA-DR' to a gene in any automated pipeline.** Two chains, several beta loci, and an assay that reads a monomorphic determinant; any single-symbol mapping is wrong in at least one direction.
  • **The MLL/COMPASS link is family-level and overexpression-based.** Treating it as a KMT2A-specific loss-of-function result would be exactly the MLL-family conflation rule 66 exists to prevent.
Still open
  1. Does HLA-DR expression on KMT2A-rearranged blasts differ from other B-precursor ALL? A bounded search finds no study that asks [E4], and it is answerable from any existing diagnostic flow database at essentially no cost.
  2. Is the MLL/COMPASS-to-CIITA-to-HLA-DRA axis [E3] retained, lost or inverted by a KMT2A fusion? The fusion loses the SET domain, so an H3K4-dependent MHC-II regulation is a concrete prediction of altered class II expression - and a possible immune-evasion mechanism that this graph has never considered.
  3. Which MLL/COMPASS subunits were the 'common subunits' in Koues 2010? Resolving that from the full text would say whether this is a KMT2A-family result at all.
Every source behind this entry (5)
  1. E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database

    The reviewed human UniProt record for the HLA-DR alpha chain is P01903 (DRA_HUMAN), primary gene name HLA-DRA, synonym HLA-DRA1, 254 aa, protein name 'HLA class II histocompatibility antigen, DR alpha chain'.

    UniProtKB reviewed entry P01903 (DRA_HUMAN) · UniProt Consortium · UniProtKB 2026
    What this evidence cannot show

    Fetched live from the UniProt REST API on 2026-09-20 with fields accession, gene_primary, gene_synonym, protein_name, length; exactly one reviewed human row whose primary gene name equals HLA-DRA. **A length note for this beat's length-check discipline:** HLA-DRA (254) and HLA-DRB1 (266) are 12 residues apart, and CLEC12A (265) sits between them - three unrelated proteins in this one beat within 12 residues of each other. Length is not a discriminator anywhere on this beat.

    Evidence that argues against this (1)
    • UniProt gives one canonical record for HLA-DRB1 while the locus has thousands of alleles; the record is a reference sequence, not the protein in any given patient. An entry asserting '266 aa' for HLA-DRB1 is asserting which record was used. UniProt Consortium 2026
  2. E2established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database

    The reviewed human UniProt record for the HLA-DR beta-1 chain is P01911 (DRB1_HUMAN), primary gene name HLA-DRB1, no listed gene synonyms, 266 aa, protein name 'HLA class II histocompatibility antigen, DRB1 beta chain'.

    UniProtKB reviewed entry P01911 (DRB1_HUMAN) · UniProt Consortium · UniProtKB 2026
    What this evidence cannot show

    Fetched live from the UniProt REST API on 2026-09-20; exactly one reviewed human row, primary gene name equals HLA-DRB1. **The canonical record represents one allele of an extremely polymorphic locus**, and HLA-DRB3/4/5 are additional expressed beta chains that also pair with DRA to form surface HLA-DR. So even naming 'the beta chain' as HLA-DRB1 is an approximation.

    Evidence that argues against this (1)
    • Because HLA-DRB3, DRB4 and DRB5 also form DR heterodimers, a measurement of surface HLA-DR is not a measurement of HLA-DRB1 even when a beta chain is meant. The gene-to-marker mapping fails in the one-to-many direction as well as the many-to-one. UniProt Consortium 2026
  3. E3moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper

    Multiple common subunits of the MLL/COMPASS complexes bind the cytokine-inducible MHC-II and CIITA promoters; overexpressing a single common MLL/COMPASS subunit significantly enhanced promoter activity and MHC-II HLA-DRA expression; and these common subunits are important for H3 lysine 4 trimethylation at MHC-II and CIITA promoters, with H3K27 trimethylation elevated when the 19S ATPase Sug1 is diminished.

    PMID 20181089DOI
    What this evidence cannot show

    Abstract read in full from raw NCBI efetch XML on 2026-09-20; full text not read. **This is wild-type MLL/COMPASS biology, not KMT2A-fusion biology** - nothing in the abstract involves a fusion protein, a leukaemic cell or KMT2A rearrangement, and the system is cytokine-inducible MHC-II regulation in mammalian cells. The subunits are described as 'common MLL/COMPASS subunits' without the abstract naming which, so this cannot be attributed to KMT2A specifically rather than to KMT2B/C/D or SETD1A/B. Overexpression, not loss of function, is the reported manipulation.

    Evidence that argues against this (1)
    • Because the effect is attributed to subunits COMMON to the MLL/COMPASS family, it is at least as likely to be a SETD1A/B or KMT2C/D function as a KMT2A one, and the brief's rule 66 warning about MLL-family symbol ambiguity applies directly. This entry therefore claims a family-level link to HLA-DRA regulation and NOT a KMT2A-specific one. Xiu Y et al. 2018
  4. E4strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.dataset

    As of 2026-09-20, PubMed returns 44 records for `"HLA-DR" AND (KMT2A OR MLL)` but only 2 for `(HLA-DRA OR HLA-DRB1) AND (KMT2A OR MLL) AND leukemia`, which title-check to a transplant alternative-donor study (PMID 25402415) and the MLL/COMPASS CIITA chromatin paper (PMID 20181089); no study found by either query reports whether HLA-DR expression on KMT2A-rearranged blasts differs from other B-precursor ALL.

    Q48 surface-antigen beat: bounded counted-absence sweep, PubMed E-utilities and Europe PMC REST · Q48-surface-antigens · Oncofusion knowledge graph (internal measurement, 2026-09-20) 2026
    What this evidence cannot show

    **Bounded counted absence.** Date 2026-09-20; tool NCBI PubMed E-utilities esearch db=pubmed; query strings as written, `querytranslation` read back for each. **Rule 67 controls passed through the identical code path:** `HLA-DRA OR HLA-DRB1` alone = 12,630 and `KMT2A OR MLL` alone = 9,229, so the instrument returns ones on both operands and the small intersection is a real intersection, not a composition failure. A separate tiab-scoped form, `"HLA-DR"[tiab] AND (KMT2A[tiab] OR MLL[tiab]) AND (infant[tiab] OR "acute lymphoblastic"[tiab])`, returned 13 records which were title-checked and are case reports, MPAL series and cell-line characterisations. **Residual:** the 44 records were title-checked, not read.

    Evidence that argues against this (1)
    • The 44-versus-2 gap measures a vocabulary split between clinical flow cytometry and immunogenetics, not necessarily a research gap. A paper reporting HLA-DR on KMT2A-rearranged blasts is doing flow cytometry and has no reason to write a gene symbol, so the small gene-symbol intersection is expected rather than diagnostic. Q48-surface-antigens 2026
  5. E5strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.dataset

    As of 2026-09-20, HLA-DR appears in 15 of this graph's 1,465 node files with no entry of its own.

    Q48 surface-antigen beat: bounded counted-absence sweep, PubMed E-utilities and Europe PMC REST · Q48-surface-antigens · Oncofusion knowledge graph (internal measurement, 2026-09-20) 2026
    What this evidence cannot show

    Measured by Python regex (`HLA-DR`) over all node JSON files on 2026-09-20; the pattern matches HLA-DRA and HLA-DRB1 as substrings too, so the count is an upper bound on mentions of the bare marker. The dispatch brief quoted 13; this run gives 15 and the difference is unreconciled - read as approximate.

    Evidence that argues against this (1)
    • Most of the 15 are panel-list mentions where HLA-DR is one marker among a dozen, so the count overstates how much substantive discussion exists. A high mention count is a signal that an entry might be missing, not proof that one is needed. Q48-surface-antigens 2026
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