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Geneweak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.Q152-aff1-only-recurrent-core

BLNK (SLP-65) - the B-cell receptor adapter, in the Q152 AFF1-only core and a known lineage-infidelity marker in myeloid leukaemia

also called SLP-65 · BASH · BLNK-s · B-cell linker protein

BLNK is the scaffold protein that holds the B-cell receptor signalling machinery together; without it B cells cannot mature. Its switch is occupied in half the KMT2A::AFF1 samples and none of the others, though the pattern is within what chance produces.

The same thing, for a scientist

BLNK (Q8WV28, 456 aa) is the SLP-65/BASH adapter downstream of the pre-B and B-cell receptor; loss causes a B-cell development block and human agammaglobulinaemia. It is one of two Q152 core genes annotated to GO:0030183 B cell differentiation. Its promoter is occupied in 4 of 8 KMT2A::AFF1 samples of GSE252378 (TB051939, p247, p279, p454) at 2.39-4.12x with the highest non-AFF1 value 1.96x, a margin of 1.22. Separately, BLNK is an established marker of lymphoid lineage infidelity in myeloid leukaemia: it is among the most up-regulated genes in RUNX1-mutated cytogenetically normal AML.

Go deeper
Lineage infidelity is the relevant prior, and it cuts both ways

BLNK expression in a myeloid context is read as lineage infidelity 3. KMT2A-rearranged disease is the archetype of lineage ambiguity - this graph holds disease-mpal and mechanism-kmt2a-mpal-mixed-phenotype on exactly that point. So BLNK occupancy in a KMT2A::AFF1 B-ALL is the expected lineage state rather than a surprise, and BLNK's absence in the myeloid-partner samples (AF9, AF10, AFDN) is equally expected on lineage grounds alone. A lineage-appropriate gene being occupied in the B-lineage arm of a mixed-lineage cohort is a lineage observation, not a fusion-specificity observation - and this is the single best reason to distrust the lymphoid appearance of the Q152 core.

Facts and figures
uniprotQ8WV28
length AA456
gene symbolBLNK
hgnc symbolBLNK
chromosome10q24.1
promoter hg38chr10:96,270,569-96,272,569 (TSS 96,271,569, minus strand, NM_013314)
shown for fusionNO - nobody has published a KMT2A-fusion occupancy or knockdown experiment on BLNK that this beat could find.
relationship to existing entriesNamed by beat Q152 because its promoter sits in the 17-gene AFF1-only recurrent core of GSE252378. Q152's headline result is that that core is NOT more recurrence than a label permutation gives (p = 0.11), and the apparent lymphoid character of the core does not survive an activity-matched null (p = 0.105 and 0.043 against a 0.025 threshold). This entry therefore does NOT claim the gene is a KMT2A::AFF1 target. It exists because the gene is real biology in this disease and had no entry. BLNK is named in 2 existing node files and had no entry.
measurements
[
  {
    "quantity": "n_aff1_samples_occupied",
    "subject": "BLNK 2 kb promoter in the KMT2A::AFF1 arm of GSE252378",
    "value": 4,
    "units": "samples of 8",
    "n": 27,
    "universe": "27 GSE252378 KMT2A-fusion samples, two-antibody 2.0x within-sample share plus per-library width-matched floor",
    "null": 2.73,
    "note": "TB051939, p247, p279, p454; occupied calls 2.39-4.12x; 0 of 19 non-AFF1, highest non-AFF1 1.96x (TB000694), separation margin 1.22. Null 2.73 is q151's per-promoter expectation across 27 samples; Q152's permutation null shows this pattern is within the chance range."
  }
]
Still open
  1. Is BLNK promoter occupancy in this deposit explained entirely by the B-lineage identity of the AFF1 samples? A B-lineage-matched comparator - the KMT2A-ENL B-ALL samples - would answer it, and this beat did not split the comparator by lineage.
  2. Does BLNK occupancy differ between p279 (B-lineage) and p318 (the same patient's lineage-switched state)? p279 is occupied and p318 is not, which is a one-patient natural experiment sitting in this dataset.
Every source behind this entry (3)
  1. E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database

    BLNK is a reviewed human UniProt entry, accession Q8WV28, 456 residues, B-cell linker protein, also known as SLP-65 and B-cell adapter containing a SH2 domain.

    UniProtKB Q8WV28 - B-cell linker protein (Homo sapiens), reviewed · UniProt Consortium · UniProtKB/Swiss-Prot 2026
    What this evidence cannot show

    gene_exact:BLNK returns one reviewed human record; no row in data/symbol-collisions.json (checked, 211 rows).

    Evidence that argues against this (1)
    • UniProt's canonical length is isoform-specific and BLNK has a documented short isoform (BLNK-s); a single length_aa is therefore an incomplete description of the protein. UniProt Consortium 2026
  2. E2moderate confidence 3 of 5: One strong study, or several smaller consistent ones.dataset

    In GSE252378 the BLNK 2 kb promoter (hg38 chr10:96,270,569-96,272,569, minus-strand refGene TSS 96,271,569, NM_013314) is occupied in 4 of 8 KMT2A::AFF1 samples (TB051939, p247, p279, p454) at min-of-replicate within-sample shares of 2.39-4.12x and in 0 of 19 non-AFF1 samples, with the highest non-AFF1 value 1.96x in TB000694 - a separation margin of 1.22.

    Q152 per-core-gene occupancy and separation margins over GSE252378 · Iqbal Lab oncofusion knowledge graph, beat Q152 · this project 2026
    What this evidence cannot show

    Q152's own label-permutation null shows a 4-of-8 AFF1-exclusive pattern is within the chance range for this rule, so this is an observation, not a target call. The comparator arm contains the AF9, AF10 and AFDN samples, which are myeloid, so BLNK's absence there is expected on lineage grounds independent of fusion partner.

    Evidence that argues against this (1)
    • BLNK is a B-lineage gene and the comparator arm contains the myeloid-partner samples, so the pattern is fully explained by lineage without invoking the fusion partner at all. The KMT2A-ENL B-ALL samples in the comparator are the control that would separate the two explanations and they were not analysed separately. NCBI Gene Expression Omnibus 2024
  3. E3moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper

    BLNK is among the most prominently up-regulated genes in RUNX1-mutated cytogenetically normal AML, alongside HOPX and DNTT, and the authors read this as lineage infidelity; in the same cohort RUNX1 mutations were significantly associated with the presence of MLL partial tandem duplications.

    RUNX1 mutations in cytogenetically normal acute myeloid leukemia are associated with a poor prognosis and up-regulation of lymphoid genes · Greif PA, Konstandin NP, Metzeler KH, Herold T, Pasalic Z, Ksienzyk B, Dufour A, Schneider F, Schneider S, Kakadia PM, Braess J, Sauerland MC, Berdel WE, Buchner T, Woermann BJ, Hiddemann W, Spiekermann K, Bohlander SK · Haematologica 97:1909-15 2012
    PMID 22689681DOI
    What this evidence cannot show

    Adult cytogenetically normal AML, n = 93 screened, 15 RUNX1-mutated. The MLL association is with partial tandem duplication, not with a KMT2A fusion, and the BLNK finding is expression-level with no occupancy data.

    Evidence that argues against this (1)
    • The RUNX1-mutated AML cohort is adult and cytogenetically normal, and its MLL association is with partial tandem duplication rather than a fusion. Nothing in it supports a KMT2A-fusion-specific reading of BLNK. Greif PA et al. 2012
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