Enumeration of the reciprocal KMT2A fusion literature: what was searched, found, rejected and could not be read

The retired-symbol rule applies here as hard as anywhere in this project: the modern spelling is the one that fails.

PMID 37726322, Effects of low-dose ionizing radiation on genomic instability in interventional radiology workers (Sci Rep 2023). Returned by AF4-MLL. Rejected: occupational biodosimetry in healthy adults, not leukaemia biology. Overturned if it reports AF4-MLL or der(4) junction frequencies in healthy individuals, which would bear directly on this graph's prenatal-origin and translocation-frequency entries.

PMID 26856288, Frequency and clinical impact of ETV6/RUNX1, AF4-MLL, and BCR/ABL fusion genes (Niger J Clin Pract 2016). Rejected: uses 'AF4-MLL' as a loose name for the t(4;11) fusion generally, a common usage that does not indicate reciprocal detection. Overturned if its methods specify a reciprocal-junction assay, in which case it is a second, independent frequency cohort - and this beat has only one.

PMID 25510485, Evidence-based RT-PCR methods for the detection of the 8 most common MLL aberrations (Leuk Res 2015). Rejected as methodological. Overturned if it contains reciprocal-junction primers, because it would then be the validated assay backbone for the paired diagnosis-relapse study this beat identifies as the field's largest missing measurement.

PMID 22931641 / 22931658 / 24602728 / 21129247, multiplex nested RT-PCR panels (Chinese-language journals). Rejected as diagnostic panel development. Overturned if any panel includes a reciprocal junction and reports its positivity rate, which would be an independent frequency estimate from a non-European population.

PMID 24817983, therapy-related B-ALL with t(4;11) after mantle cell lymphoma treatment. Rejected: single case, no reciprocal analysis. Overturned if the case reports reciprocal status - a therapy-related t(4;11) would be a useful contrast to the prenatal infant disease.

PMID 27856324, MLL-AF4 binds directly to a BCL-2 specific enhancer (Exp Hematol 2017). Rejected: direct product only. Overturned if the ChIP reagent used cannot distinguish the reciprocal product, which would make its occupancy calls ambiguous in the same way the anti-MLL-C studies are.

PMID 20362031, Activation of Ras-dependent Elk-1 activity by MLL-AF4 family fusion oncoproteins (Exp Hematol 2010). Rejected: assays MLL-AF4, MLL-AF5q31 and MLL-LAF4, all direct products. Overturned if anyone tests the reciprocal product in the same Elk-1 reporter, since RAS pathway activation is the one recurrent secondary lesion in this disease.

PMID 35468859, MLL-AF4 and a murinized pSer-variant thereof are turning on the nucleolar stress pathway (Cell Biosci 2022). Read and deliberately not cited in a dedicated entry, which is a different category from rejection: it reports that AF4-MLL cooperates at the molecular level with human MLL-AF4 but not with the murinized pSer variant, which is a direct and unused argument that murine-humanised MLL-Af4 models are not reciprocal-competent. It belongs in a future entry on model-system validity and this beat ran out of scope, not out of interest.

PMID 20952059, Sanders DS, Muntean AG, Hess JL, Significance of AF4-MLL reciprocal fusion in t(4;11) leukemias?, Leuk Res 2011. The title asserts a question about exactly this beat's subject from an independent and authoritative group. PubMed returns no abstract; Europe PMC resultType=core returns no pmcid, so routes 2, 3 and 4 have nothing to address 3. Confidence weak, and this entry does not state what the commentary argues.

PMID 21277021, Kumar AR et al., Authors' comments: t(4;11) leukemias display addiction to MLL-AF4 but not to AF4-MLL, Leuk Res 2011. Same result: no abstract, no PMCID, all four routes fail 3. Both are cited elsewhere in this beat only for the fact that a formal exchange occurred, never for content.

These two are the single most annoying gap in the beat, because together they are the field's only explicit published debate about whether the reciprocal product matters, and neither half can be read from any free route.

Two papers were read in full text: 34489550 via Europe PMC fullTextXML (PMC8530991, 40,194 characters) and 37019990 likewise (PMC10169636, 86,330 characters). Reading the second changed the beat materially and is the clearest argument in this entry for reading rather than abstracting. Three things were in the body and in no abstract: the exact spliced-fusion counts across ten partners including AFF1 at 1 of 1,262, which establishes that t(4;11) has effectively no spliced-fusion class; the KMT2A* protein - a 5'-truncated KMT2A from a gene-internal promoter upstream of exon 12 that the authors state cannot bind menin, LEDGF or MYB while retaining all enzymatic function - which became an entry of its own and is the largest menin-blind KMT2A species this graph has; and the statement that breakpoints upstream of exon 11 leave PHD domain I intact on the reciprocal side while breaks within or downstream of exon 11 impair CYP33 binding and PHD1 homodimerisation, together with the observation that ALL breakpoint preference switches from intron 11 to intron 9 at about 6 months of age.

PMIDs 17130830, 15221006, 21233834, 22570686, 26329759, 25402609, 20869771, 17410185, 25016062, 16983345 and 32294539 were used from abstracts; every numeric claim taken from an abstract is marked as such in its caveat. The two that most deserve full-text reading next are 17410185 (the genomic structure of reciprocal-negative t(4;11), whose n is not in the abstract) and 21030982 (the sixteen complex constituents, named only by activity class in the abstract). 30679323 is open access in PMC and its HOXA-by-reciprocal cross-tabulation should be read before that collinearity is leaned on further.