CD65 - a neutral glycolipid epitope (V3FucnLc8Cer), no gene, and the CD number that was split in two because its antibodies did not agree
also called CD65 · CDw65 · VIM-8 · VIM-11 · V3FucnLc8Cer · ceramide octasaccharide · fucoganglioside
CD65 is not a protein and not even a sugar on a protein - it is a sugar chain on a fat molecule in the cell membrane, so no gene makes it. It is also a cautionary tale: the antibodies originally grouped under this one CD number turned out to recognise two different things, which is why CD65 and CD65s are separate entries here.
The same thing, for a scientist
CD65 is a **glycosphingolipid** epitope. Kniep and colleagues resolved the CDw65 cluster at the molecular level: antibodies VIM-8 and VIM-11 bind the **neutral glycolipid V3FucnLc8Cer**, while VIM-2 binds the **sialylated** ganglioside, and the two behave oppositely under neuraminidase - VIM-2 binding is abolished by *Vibrio cholerae* neuraminidase while VIM-8 and VIM-11 binding is **enhanced** by it. The authors' conclusion is explicit: *VIM-2 and the other CDw65 antibodies represented two different antigen specificities* [E1]. **That sentence is the whole reason this beat writes CD65 and CD65s as two entries.** A single CD designation covered two chemically distinct antigens on the same cells, distinguished only by a sialic acid, and the distinction was invisible until glycolipid-level binding studies were done. **A CD number is a reagent cluster, not a molecule** - and here the cluster was wrong. **In this disease.** CD65 appears in **13** node files of this graph, measured 2026-09-20, with no entry [E4]. It is one of the myeloid antigens co-expressed on KMT2A-rearranged pro-B blasts. **But the antigen that carries the discriminating signal in the best-characterised series is CD65s, not CD65** [see `target-cd65s-sialylated-vim2-ganglioside`], and entries that write 'CD65' where the source says 'CD65s' are making a real error, not a typographical one. **No gene encodes it** [E3]. It is assembled by glycosyltransferases acting on a ceramide-anchored lacto-series chain; the alpha-1,3-fucosylation step is the same FUT4-type chemistry that makes CD15 [E2].
The two specificities, and how to tell which one a paper means
Why type: "target" and not gene-. data/graph/SCHEMA.md has no antigen or glycan node type; target is the closest legal type for a bindable cell-surface determinant. An id beginning gene- would be flatly wrong here - HGNC returns no record at all for CD65, neither as an approved symbol, an alias nor a previous symbol. Unlike CD15, which resolves misleadingly to FUT4, CD65 returns an honest blank, and the blank is the safer failure. See concept-a-cd-number-is-not-a-gene.
| antibody | binds | neuraminidase effect |
|---|---|---|
| VIM-2 | sialylated: X3-NeuAc-VII3Fuc-nLc10Cer (VIM-2 dodecasaccharide) and VIII3-NeuAc-V3Fuc-nLc8Cer (VIM-2 decasaccharide) | binding abolished |
| VIM-8, VIM-11 | neutral: V3FucnLc8Cer (the asialo form of the VIM-2 decasaccharide) | binding enhanced |
Practical rule for reading a flow report or a paper: if the marker is written CD65s or the antibody is VIM-2, it is the sialylated ganglioside. If it is written CD65 or CDw65 with VIM-8 or VIM-11, it is the neutral glycolipid. If the paper says only 'CD65' and names no clone, the antigen is not determined by the text and this graph should record it unresolved rather than guess - the same discipline the brief requires for MLL2/MLL4.
And the neuraminidase asymmetry has a bench consequence: any sample preparation involving neuraminidase, or any disease state with altered sialidase activity, moves these two antigens in opposite directions. A CD65/CD65s ratio is therefore not a stable property of a cell.
Distribution in normal and leukaemic myeloid cells
The VIM-2 epitope is carried by three or more gangliosides; two strongly immunoreactive species with ten and twelve monosaccharides were found in myeloid cells, and normal neutrophils and CML cells carried much greater quantities of the VIM-2 gangliosides than acute leukaemia cells, with acute leukaemia cells showing a predominance of short-chain gangliosides. Both CML cells and normal neutrophils express a shorter-chain VIM-2 ganglioside not detected in AML cells 2.
In AML, the VIM-2 antigen was more strongly expressed than the SSEA-1 (CD15) antigen, and both antibodies stained acute myelomonocytic leukaemia cells more intensely than AML cells 2. Expression tracks maturation: FUT4 upregulation at the promyelocyte stage raises Lewis-x, VIM-2 and Lewis-y together while lowering sialyl-Lewis-x 5.
| antigen class | neutral glycosphingolipid epitope (ceramide-anchored, lacto-series) |
|---|---|
| chemical structure | V3FucnLc8Cer - the asialo form of the VIM-2 decasaccharide |
| neuraminidase effect | binding ENHANCED by Vibrio cholerae neuraminidase |
| encoded by a gene | false |
| why not a gene | a glycolipid, not a polypeptide: a fucosylated lacto-series glycan on ceramide, built by a series of glycosyltransferases |
| hgnc lookup 2026 09 20 | no record for the string CD65 as approved symbol, alias or free-text search |
| sibling antigen | target-cd65s-sialylated-vim2-ganglioside |
defining antibodies
[ "VIM-8", "VIM-11" ]
graph mentions 2026 09 20
{
"CD65": 13,
"CD65s": 8
}- **Not a therapeutic target.** CD65 is abundant on normal neutrophils and more abundant there than on acute leukaemia cells [E2]; a CD65-directed agent would have inverse selectivity.
- **A CD65/CD65s ratio is not a stable cell property.** The two antigens respond to neuraminidase in opposite directions [E1], so sample handling and sialidase activity move them apart.
- **Pooling old CD65 series is unsafe.** The cluster contained two specificities before 1996 and much of the clinical literature does not name its clone.
- Which anti-CD65 clones in current diagnostic panels have VIM-2-like versus VIM-8-like specificity? Without that, a modern 'CD65' flow result cannot be mapped onto either antigen described here.
- Do KMT2A-rearranged blasts carry the neutral antigen, the sialylated one, or both? The defining series [see `target-cd65s-sialylated-vim2-ganglioside`] reports CD65s; no source read on this beat reports neutral CD65 separately in KMT2A-rearranged disease.
- Which sialyltransferase converts the neutral epitope into CD65s in myeloid cells? Naming it would give CD65s the same gene-keyed bridge FUT4 gives CD15, and this beat did not establish it.
- E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper
Three antibodies of the CDw65 cluster were studied at the molecular level: VIM-2 binding is abolished by Vibrio cholerae neuraminidase whereas VIM-8 and VIM-11 show enhanced binding to neuraminidase-treated cells; VIM-2 strongly bound the sialylated VIM-2 decasaccharide VIII3-NeuAc-V3Fuc-nLc8Cer while VIM-8 and VIM-11 did not, and conversely the asialo form V3FucnLc8Cer was not recognised by VIM-2 but bound VIM-8 and VIM-11 strongly - so VIM-2 and the other CDw65 antibodies represent two different antigen specificities.
The CDw65 monoclonal antibodies VIM-8 and VIM-11 bind to the neutral glycolipid V3FucnLc8Cer. · Kniep B, Peter-Katalinic J, Muthing J, Majdic O, Pickl WF, Knapp W · J Biochem 1996What this evidence cannot show
Abstract read in full from raw NCBI efetch XML on 2026-09-20; full text not read. 1996 glycolipid binding study on purified antigens; three antibodies only, and the CDw65 cluster as defined at the IVth and Vth Human Leukocyte Differentiation Antigen Workshops contained more. Whether any given modern anti-CD65 clone behaves like VIM-2 or like VIM-8/VIM-11 is **not** established by this paper and would have to be checked per reagent.
Evidence that argues against this (1)
- Because this splits one CD number into two specificities, any clinical series predating or ignoring the split reports 'CD65' positivity that could be either antigen. That makes older CD65 prevalence figures in leukaemia difficult to pool, and this entry does not attempt to pool them. Macher BA et al. 1990
- E2strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
The VIM-2 epitope is carried by three or more gangliosides in myeloid cells, with two strongly immunoreactive species of ten and twelve monosaccharides; expression of both VIM-2 and SSEA-1 antigens is restricted to normal and leukaemic myeloid cells; VIM-2 is more strongly expressed than SSEA-1 in acute leukaemia marrows; normal neutrophils and CML granulocytes carry much greater quantities of VIM-2 gangliosides than acute leukaemia cells; and lymphocytic leukaemia marrows were negative for both.
Distribution of VIM-2 and SSEA-1 glycoconjugate epitopes among human leukocytes and leukemia cells. · Macher BA, Beckstead JH · Leuk Res 1990What this evidence cannot show
Abstract read in full from raw NCBI efetch XML on 2026-09-20; full text not read. 1990 immunohistochemistry on plastic sections plus TLC immunostaining, not flow cytometry; sample numbers not given in the abstract. The 'lymphocytic leukaemia negative' result predates recognition of KMT2A-rearranged pro-B ALL as a myeloid-antigen-co-expressing entity and is in tension with the CD65s positivity that defines that phenotype - see `target-cd65s-sialylated-vim2-ganglioside`.
Evidence that argues against this (1)
- This paper's own framing is at the level of VIM-2 (the sialylated specificity), not of the neutral VIM-8/VIM-11 antigen, so it is better evidence for CD65s than for CD65 as this entry defines them. It is cited here for the shared myeloid-restriction and maturation behaviour, and that borrowing is itself an instance of the conflation this entry warns about. Kniep B et al. 1996
- E3established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
HGNC returns no record for the string CD65, neither as an approved symbol, an alias symbol nor via free-text search - unlike CD15, which resolves to FUT4 as a previous symbol, and CD371, which resolves to CLEC12A as an alias.
HGNC record HGNC:4015 (FUT4) · HUGO Gene Nomenclature Committee · HGNC 2026What this evidence cannot show
Measured 2026-09-20 against the live HGNC REST API: `/search/alias_symbol/CD65` and `/search/CD65` both returned empty document lists, while the same two calls for CD15 returned FUT4 and for CD371 returned CLEC12A. **This is a negative result from a lookup and is bounded by the tool and the date only** - it demonstrates that the string is unresolvable in HGNC today, not that no gene relates to the antigen. The citation attached is the FUT4 record, because it is the positive control that shows the same code path returns records when a record exists; there is no HGNC record for CD65 to cite.
Evidence that argues against this (1)
- An empty HGNC response is exactly the shape of result the brief warns about - well formed, confident and empty. It is recorded as a result here only because a positive control through the identical call returned FUT4 and CLEC12A on the same day. HUGO Gene Nomenclature Committee 2026
- E4strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.dataset
As of 2026-09-20, CD65 appears in 13 of this graph's 1,465 node files and CD65s in 8, with no entry for either; PubMed returns 36 records for `CD65 AND leukemia`, 10 for `CD65 AND (MLL OR KMT2A)` and 15 for the bare token `CD65s`.
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) 2026What this evidence cannot show
In-graph counts by Python regex over node JSON on 2026-09-20 with word boundaries (`\bCD65\b`, `\bCD65s\b`); note that `\bCD65\b` does **not** match the string CD65s, so the two counts are disjoint and the 13 is CD65-proper. The dispatch brief quoted 12 and 7; this run gives 13 and 8, and the one-entry differences are unreconciled - read them as approximate. PubMed counts from E-utilities esearch with `querytranslation` read back. **Rule 67 controls:** `CD65 AND leukemia` = 36 and `KMT2A OR MLL` = 9,229 are the non-zero controls; no zero is recorded in this entry.
Evidence that argues against this (1)
- PubMed's bare `CD65` token has no MeSH or Supplementary Concept expansion (unlike CD15, which expands to 'lewis x antigen'), so the CD65 counts are literal string matches and will miss papers that write CDw65, VIM-2, VIM-8 or the glycolipid name. The true literature is larger than 36 and this entry does not claim otherwise. Q48-surface-antigens 2026
- E5moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper
In myeloid lines spanning maturation stages, the Fuc-TIV (FUT4) mRNA peak at the HL-60 promyelocyte stage correlated with upregulation of Lewis-x, VIM-2 and Lewis-y and transitory downregulation of sialyl-Lewis-x.
Independent regulation of Fuc-TIV and Fuc-TVII genes leading to modulation of cell surface antigen expression in developing myeloid cells. · Clarke JL, Watkins WM · Glycobiology 1997What this evidence cannot show
Abstract read in full from raw NCBI efetch XML on 2026-09-20; full text not read. Cell lines as maturation proxies; correlation only, no knockdown. VIM-2 here is the sialylated specificity, so this evidence item speaks more directly to CD65s than to the neutral CD65 antigen - the shared alpha-1,3-fucosylation step is what licenses citing it in both entries, and that limitation is stated rather than hidden.
Evidence that argues against this (1)
- That FUT4 upregulation raises VIM-2 while lowering sialyl-Lewis-x shows that these glycan antigens are coupled by substrate competition. Any model treating CD65, CD65s and CD15 as independent markers on a flow panel is therefore biochemically wrong, even though it is clinically conventional. Kadirvelraj R et al. 2023
the sialylated and neutral halves of one CD designation, with opposite neuraminidase responses
shares the alpha-1,3-fucosylation step with CD15; FUT4 upregulation raises VIM-2 and Lewis-x together
- supports →The named-but-unwritten queue is keyed on gene symbols, so CD15 is invisible to it at 23 entries
HGNC returns no record at all for CD65 - the honest blank, against CD15's misleading resolution to FUT4
- ← related toA CD number names a reagent cluster, not a molecule - and four different things can sit behind one
the one-number-two-antigens case: CDw65 covered two specificities