What this beat searched, what it rejected, and the two papers it could not read - after a fifth route rescued the third
also called MRD enumeration · MRD bounded rejection · MRD search record
A record of exactly which searches were run to survey how this leukaemia is measured, which papers were found and deliberately not used, and which papers could be found but not read. It exists so that someone repeating this survey next year repeats the decisions as well as the searches.
The same thing, for a scientist
Five MRD assay classes were enumerated for KMT2A-rearranged and infant ALL: genomic breakpoint qPCR, fusion transcript RT-qPCR, Ig/TCR ASO-PCR, multiparameter flow cytometry, and sequencing-based MRD, plus plasma ctDNA as a sixth in preclinical status. Queries, counts and query translations are recorded below. **Three counted absences** were established: no cohort study of sequencing-based MRD in infant KMT2A-rearranged ALL; no head-to-head comparison of genomic-breakpoint against fusion-transcript MRD in infants; and no trial of a menin inhibitor reporting paired phenotype-based and lineage-independent molecular MRD. **Three papers were found, judged on-beat, and failed all four PMC routes** - the Interfant-06 primary report [E1], the Interfant-99 primary report [E2] and the COG P9407 partner-gene study [E3], each with `pmcid: null`, which makes routes 2, 3 and 4 structurally unavailable rather than merely failed. **A fifth route - resolving the DOI to the publisher's own page - recovered the third of them** [E3], because Haematologica is fully open access and does not deposit in PMC. It did not recover the other two. The correction matters more than the paper: **the four-route test is a test of PMC, not a test of readability.** Bounded rejections are listed with a reason and with what would change the decision.
Queries run, with counts and translations
Run 2026-09-20 against PubMed esearch. Multi-word phrases quoted and bounded with [tiab] throughout, per the rule that unquoted phrases explode into per-word synonym sets; querytranslation was read on positive counts as well as on zeros. No karyotype string was placed in a parenthesised query.
| query | records |
|---|---|
"minimal residual disease"[tiab] AND infant[tiab] AND (KMT2A[tiab] OR MLL[tiab]) | 32 |
"genomic breakpoint"[tiab] AND "minimal residual disease"[tiab] | 7 |
(infant[tiab] OR infants[tiab]) AND (KMT2A[tiab] OR MLL[tiab]) AND "measurable residual disease"[tiab] | 2 |
infant[tiab] AND (MLL[tiab] OR KMT2A[tiab]) AND ("immunoglobulin gene rearrangement"[tiab] OR "immunoglobulin gene rearrangements"[tiab] OR "Ig gene rearrangements"[tiab]) | 1 |
oligoclonal[tiab] AND lymphoblastic[tiab] AND "residual disease"[tiab] | 22 |
infant[tiab] AND "flow cytometry"[tiab] AND "residual disease"[tiab] AND leukemia[tiab] | 9 |
"high-throughput sequencing"[tiab] AND "residual disease"[tiab] AND lymphoblastic[tiab] | 33 |
(infant[tiab] OR infants[tiab]) AND (KMT2A[tiab] OR MLL[tiab]) AND ("minimal residual disease"[tiab] OR "measurable residual disease"[tiab]) AND ("next-generation sequencing"[tiab] OR "high-throughput sequencing"[tiab] OR "clonoSEQ"[tiab] OR "immunosequencing"[tiab]) | 2 |
(infant[tiab] OR infants[tiab]) AND leukemia[tiab] AND "clonoSEQ"[tiab] | 1 |
"circulating tumor DNA"[tiab] AND (KMT2A[tiab] OR MLL[tiab]) AND leukemia[tiab] | 1 |
"lineage switch"[tiab] AND ("residual disease"[tiab] OR "flow cytometry"[tiab]) | 24 |
"digital PCR"[tiab] AND "residual disease"[tiab] AND lymphoblastic[tiab] | 26 |
"Interfant-06"[tiab] AND ("high risk"[tiab] OR "risk group"[tiab] OR stratification[tiab]) | 7 |
Both the current symbol KMT2A and the retired symbol MLL were used in every gene-keyed query, because retrieval in this literature is still dominated by the retired symbol: the recombinome series itself publishes under both names across editions.
Bounded rejections: found, on-topic-looking, not used
Three lines each, with the identifier, the reason and what would change the decision.
- PMID 34440129 - BTK, NUTM2A, and PRPF19 Are Novel KMT2A Partner Genes in Childhood Acute Leukemia. Uses targeted NGS on DNA and RNA and states that the characterisations allow tracing MRD dynamics. Rejected as an MRD study: sequencing is used here to establish a target, not to quantify residual disease, which is the same role LDI-PCR plays. Cited in the sequencing entry as a rejection rather than as evidence. Would change: if the group published the MRD time courses those assays produced.
- PMID 41195225 - a 302-patient childhood ALL molecular-genetics cohort including MLL fusions and MRD monitoring. Rejected: MRD is reported only as positivity rates by gene group with no assay description, no infant subgroup and no KMT2A-rearranged analysis. Would change: an infant or KMT2A-stratified reanalysis with assay details.
- PMID 35933523 - MRD in BCR::ABL1-positive ALL, genomic breakpoint versus Ig/TCR. Not rejected but deliberately used only as an analogy in
concept-mrd-monitoring-genomic-breakpoint; it is a different fusion with an established multilineage subset that has no demonstrated KMT2A counterpart. Would change: evidence of multilineage involvement in KMT2A-rearranged infant ALL. - PMID 31681710 - a review of flow-cytometric MRD in paediatric AML that also touches quantitative genomic breakpoint PCR. Rejected as primary evidence: paediatric AML generally, review not primary, and the graph already has better-matched primary sources for both assays. Would change: nothing; it remains a useful map.
- PMID 40343433 - Croatian paediatric ALL cohort with day-15 flow MRD predictors. Rejected: explicitly non-infant (379 non-infant patients analysed) and no KMT2A-rearranged analysis. Would change: an infant arm.
- PMID 19995953 - the only hit for infant, MLL and immunoglobulin gene rearrangement terms together. Rejected as off-beat: it is about mesenchymal stromal cells carrying MLL-AF4 and uses the absence of monoclonal Ig rearrangements in those cells as an argument about cell of origin, not about MRD. It is a good example of a query returning a topically perfect-looking single hit that answers a different question.
- The general adult ALL MRD literature (EuroMRD standardisation, ddPCR quality control, ABL-class fusion MRD) was read and used only where it establishes method properties, never as evidence about infants. Would change: any of these cohorts reporting a KMT2A-rearranged or infant subgroup.
Found and on-beat: two unreadable, one rescued by a fifth route
For each, the identifier and what the title asserts. For the two that remain unreadable, no inference about content beyond the abstract is recorded anywhere in this beat, and claims cited to them are marked abstract-only in their caveats.
| PMID | EPMC core | routes 2-4 | fifth route: DOI to publisher | outcome |
|---|---|---|---|---|
| 31283407 1 Interfant-06 | pmcid: null, isOpenAccess: N, inEPMC: N | structurally unavailable | ascopubs.org HTTP 403 | unreadable |
| 17658395 2 Interfant-99 | pmcid: null, isOpenAccess: N, inEPMC: N | structurally unavailable | Elsevier redirect stub, 13 characters stripped | unreadable |
| 36861410 3 COG P9407 | pmcid: null, isOpenAccess: N, inEPMC: N, empty abstract in PubMed | structurally unavailable | haematologica.org, 27,880 characters stripped | read in full |
The rule this changes. Every route in the four-route test - {PMCID}/fullTextXML, efetch db=pmc, and the PMC HTML page - requires a PMCID, so when the Europe PMC core record returns pmcid: null the test does not fail, it never runs, and it returns a clean structural negative that looks identical to a real one. A journal can be fully open access and absent from PMC. Resolve the DOI to the publisher before writing 'unreadable'. Tried here on all three, it succeeded for one and failed for two, which is what a real additional route looks like rather than a universal rescue.
A markup trap inside the rescue, worth the same attention. Unescaping HTML entities before stripping tags destroys content: <50x10 9 /L became <50x10 9 /L and was then deleted as a tag, turning WBC count <50x10^9/L into WBC count - a comparison with no number in it, in a sentence that still parses. Same family as the italicised-gene-symbol trap. Strip tags first, unescape entities second.
What the rescue was worth. P9407 is the only study that applies two different risk groupings to the same infant cohort, and it finds the Interfant grouping built on WBC >300 x10^9/L discriminates worse than a cut at 50 x10^9/L, worse than age above or below 90 days, and worse than partner gene 3. It also supplies the only published biological argument for any cut-point in this disease - microarray separation of AFF1 cases at about 90 days - which is the comparator that makes the absence of such an argument for WBC 300 meaningful. That entire argument in concept-wbc-300-threshold-is-an-administrative-choice would not exist if the fifth route had not been tried.
The two that remain unreadable still cost something specific. The Interfant-06 full text is the document that would resolve the direction of the high-risk age criterion, where its own published abstract says older than 6 months and the trial registry, the group's MRD paper and now COG P9407 all say under 6 months. Three sources against one, and the one that would settle it cannot be opened.
| script | none; search record and manual adjudication |
|---|---|
| status | run |
| result summary | five clinical MRD assay classes enumerated plus one preclinical; three counted absences; six bounded rejections; three on-beat papers failed all four PMC routes and one of the three was recovered by resolving its DOI to the publisher |
inputs
[ "PubMed esearch 2026-09-20", "Europe PMC core records", "ClinicalTrials.gov API v2" ]
assay classes enumerated
[ "genomic breakpoint qPCR", "fusion transcript RT-qPCR", "Ig/TCR ASO-PCR", "multiparameter flow cytometry", "sequencing-based (IGH/TRG amplicon)", "plasma ctDNA ddPCR (preclinical)" ]
counted absences
[ "no cohort study of sequencing-based MRD in infant KMT2A-rearranged ALL (2 records, neither a cohort)", "no head-to-head comparison of genomic-breakpoint versus fusion-transcript MRD in infants", "no menin-inhibitor trial reporting paired phenotype-based and lineage-independent molecular MRD" ]
bounded rejections — the numbers behind the chart
[
{
"pmid": "34440129",
"reason": "target discovery, not MRD measurement",
"would_change": "published MRD time courses from those assays",
"title": "BTK, NUTM2A, and PRPF19 Are Novel KMT2A Partner Genes in Childhood Acute Leukemia.",
"authors": "Zerkalenkova E, Lebedeva S, Borkovskaia A, et al.",
"venue": "Biomedicines",
"year": 2021,
"title_provenance": "Title/authors/venue backfilled from PubMed esummary on 2026-09-20 because this citation stored a bare PMID with no title, which made it unscoreable by verify-citations.py. BACKFILLING IS NOT VERIFICATION: it confirms the PMID resolves to a real paper, not that this is the right paper for the claim. That still requires reading."
},
{
"pmid": "41195225",
"reason": "MRD reported as positivity rates by gene group; no assay detail, no infant or KMT2A-r subgroup",
"would_change": "infant or KMT2A-stratified reanalysis with assay details",
"title": "Molecular genetic characteristics and clinical significance of childhood acute lymphoblastic leukemia.",
"authors": "Zhu Z, Yan J",
"venue": "Front Pediatr",
"year": 2025,
"title_provenance": "Title/authors/venue backfilled from PubMed esummary on 2026-09-20 because this citation stored a bare PMID with no title, which made it unscoreable by verify-citations.py. BACKFILLING IS NOT VERIFICATION: it confirms the PMID resolves to a real paper, not that this is the right paper for the claim. That still requires reading."
},
{
"pmid": "31681710",
"reason": "review of flow MRD in paediatric AML; better-matched primary sources exist",
"would_change": "nothing; retained as a map",
"title": "Flow-Cytometric Monitoring of Minimal Residual Disease in Pediatric Patients With Acute Myeloid Leukemia: Recent Advances and Future Strategies.",
"authors": "Buldini B, Maurer-Granofszky M, Varotto E, et al.",
"venue": "Front Pediatr",
"year": 2019,
"title_provenance": "Title/authors/venue backfilled from PubMed esummary on 2026-09-20 because this citation stored a bare PMID with no title, which made it unscoreable by verify-citations.py. BACKFILLING IS NOT VERIFICATION: it confirms the PMID resolves to a real paper, not that this is the right paper for the claim. That still requires reading."
},
{
"pmid": "40343433",
"reason": "explicitly non-infant cohort, no KMT2A-r analysis",
"would_change": "an infant arm",
"title": "Disease characteristics and outcomes of Croatian pediatric patients with acute lymphoblastic leukemia: pretreatment immunophenotypic predictors of high bone marrow minimal residual disease on day 15 of treatment.",
"authors": "Dubravčić K, Lasan Trčić R, Bilić E, et al.",
"venue": "Croat Med J",
"year": 2025,
"title_provenance": "Title/authors/venue backfilled from PubMed esummary on 2026-09-20 because this citation stored a bare PMID with no title, which made it unscoreable by verify-citations.py. BACKFILLING IS NOT VERIFICATION: it confirms the PMID resolves to a real paper, not that this is the right paper for the claim. That still requires reading."
},
{
"pmid": "19995953",
"reason": "mesenchymal stromal cells carrying MLL-AF4; Ig rearrangement used as a cell-of-origin argument, not MRD",
"would_change": "nothing; recorded because the query returns it as an apparently perfect single hit",
"title": "Bone marrow mesenchymal stem cells from infants with MLL-AF4+ acute leukemia harbor and express the MLL-AF4 fusion gene.",
"authors": "Menendez P, Catalina P, Rodríguez R, et al.",
"venue": "J Exp Med",
"year": 2009,
"title_provenance": "Title/authors/venue backfilled from PubMed esummary on 2026-09-20 because this citation stored a bare PMID with no title, which made it unscoreable by verify-citations.py. BACKFILLING IS NOT VERIFICATION: it confirms the PMID resolves to a real paper, not that this is the right paper for the claim. That still requires reading."
},
{
"pmid": "35933523",
"reason": "BCR::ABL1, used as analogy only; different fusion with an established multilineage subset",
"would_change": "evidence of multilineage involvement in KMT2A-rearranged infant ALL",
"title": "Minimal residual disease in BCR::ABL1-positive acute lymphoblastic leukemia: different significance in typical ALL and in CML-like disease.",
"authors": "Zuna J, Hovorkova L, Krotka J, et al.",
"venue": "Leukemia",
"year": 2022,
"title_provenance": "Title/authors/venue backfilled from PubMed esummary on 2026-09-20 because this citation stored a bare PMID with no title, which made it unscoreable by verify-citations.py. BACKFILLING IS NOT VERIFICATION: it confirms the PMID resolves to a real paper, not that this is the right paper for the claim. That still requires reading."
}
]unreadable after all four routes
[
{
"pmid": "31283407",
"epmc": "pmcid null, isOpenAccess N, inEPMC N",
"fifth_route": "ascopubs.org via DOI: HTTP 403",
"title_asserts": "outcome of 651 infants on Interfant-06, international phase III randomised study",
"cost": "cannot resolve the direction of the high-risk age criterion",
"title": "Outcome of Infants Younger Than 1 Year With Acute Lymphoblastic Leukemia Treated With the Interfant-06 Protocol: Results From an International Phase III Randomized Study.",
"authors": "Pieters R, De Lorenzo P, Ancliffe P, et al.",
"venue": "J Clin Oncol",
"year": 2019,
"title_provenance": "Title/authors/venue backfilled from PubMed esummary on 2026-09-20 because this citation stored a bare PMID with no title, which made it unscoreable by verify-citations.py. BACKFILLING IS NOT VERIFICATION: it confirms the PMID resolves to a real paper, not that this is the right paper for the claim. That still requires reading."
},
{
"pmid": "17658395",
"epmc": "pmcid null, isOpenAccess N, inEPMC N",
"fifth_route": "Elsevier via DOI: 13-character redirect stub",
"title_asserts": "Interfant-99 treatment protocol, observational study and multicentre randomised trial",
"cost": "cannot check whether a WBC threshold is defined in the full text",
"title": "A treatment protocol for infants younger than 1 year with acute lymphoblastic leukaemia (Interfant-99): an observational study and a multicentre randomised trial.",
"authors": "Pieters R, Schrappe M, De Lorenzo P, et al.",
"venue": "Lancet",
"year": 2007,
"title_provenance": "Title/authors/venue backfilled from PubMed esummary on 2026-09-20 because this citation stored a bare PMID with no title, which made it unscoreable by verify-citations.py. BACKFILLING IS NOT VERIFICATION: it confirms the PMID resolves to a real paper, not that this is the right paper for the claim. That still requires reading."
}
]rescued by a fifth route
[
{
"pmid": "36861410",
"epmc": "pmcid null, isOpenAccess N, inEPMC N, empty abstract in PubMed",
"fifth_route": "https://doi.org/10.3324/haematol.2022.281552 -> haematologica.org, 27880 characters stripped",
"why": "Haematologica is fully open access and does not deposit in PMC",
"what_it_was_worth": "the only head-to-head of two infant risk groupings on one cohort, and the only published biological argument for any cut-point in this disease",
"title": "KMT2A partner genes in infant acute lymphoblastic leukemia have prognostic significance and correlate with age, white blood cell count, sex, and central nervous system involvement: a Children's Oncology Group P9407 trial study.",
"authors": "Robinson BW, Kairalla JA, Devidas M, et al.",
"venue": "Haematologica",
"year": 2023,
"title_provenance": "Title/authors/venue backfilled from PubMed esummary on 2026-09-20 because this citation stored a bare PMID with no title, which made it unscoreable by verify-citations.py. BACKFILLING IS NOT VERIFICATION: it confirms the PMID resolves to a real paper, not that this is the right paper for the claim. That still requires reading."
}
]methodological corrections produced
[ "the four-route unreadable test is a test of PMC, not of readability: all four routes require a PMCID, so pmcid null returns a structural negative indistinguishable from a real one. Resolve the DOI to the publisher as a fifth route.", "strip HTML tags BEFORE unescaping entities: unescaping first turns <50 into <50, which the tag stripper then deletes, leaving a comparison with no number in a sentence that still parses" ]
- A counted absence with well-written bounds is the most trustworthy-looking thing this beat produced and is also the easiest to get wrong. The sequencing-MRD absence rests on a phrase set that does not include every vendor name or every spelling of immunosequencing, and a single missed alias would overturn it.
- This entry asserted, in its first version, that three papers were unreadable. One of them was fully open access and one HTTP request away. An unreadable verdict reached by a procedure that never ran is the same failure the procedure exists to prevent, and it was written confidently.
- The two papers that remain unreadable are the two most authoritative sources on infant ALL treatment and risk stratification. The graph's clinical layer rests on their abstracts plus a trial registry, which is secondary description of primary documents nobody in this project can open.
- Recording rejections creates a temptation to reject less, because each rejection now costs three lines of writing. The six listed here are the ones a reader would expect to see cited; the many off-disease and off-organism hits are not recorded, which is itself a judgement about what a reader would expect.
- Does the Interfant-06 full text define the high-risk age criterion as under or over 6 months? Its own abstract says over; the registry, the group's MRD paper and COG P9407 all say under. The primary document is paywalled, returns HTTP 403 to the publisher route, and has no PMCID.
- Does the Interfant-99 full text state where the 300 x10^9/L WBC threshold came from? The abstract says only very high white blood cell count, and the Elsevier DOI resolves to a redirect stub.
- How many other entries in this graph carry an 'unreadable' verdict that was reached by the four PMC routes alone, on a paper published in an open-access journal that does not deposit in PMC? The verdict is cheap to re-test and this beat found one such paper in three.
- Are there conference abstracts reporting sequencing-based MRD in infant KMT2A-rearranged ALL? PubMed does not index them, so the counted absence is bounded to the peer-reviewed literature.
- E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper
The Interfant-06 primary report describes 651 infants younger than 1 year with acute lymphoblastic leukaemia treated on an international phase III randomised study, with 6-year event-free survival 46.1% and overall survival 58.2%, and a high-risk group defined using KMT2A status, age relative to 6 months, WBC count and prednisone response.
Outcome of Infants Younger Than 1 Year With Acute Lymphoblastic Leukemia Treated With the Interfant-06 Protocol: Results From an International Phase III Randomized Study. · Pieters R, De Lorenzo P, Ancliffe P, et al. · J Clin Oncol 2019What this evidence cannot show
Abstract only. The Europe PMC core record returns pmcid null with isOpenAccess N and inEPMC N, so the fullTextXML, efetch db=pmc and PMC HTML routes are structurally unavailable rather than failed. Every claim cited to this paper in this beat is drawn from the abstract and is marked as such, and the beat records rather than resolves the contradiction between this abstract's high-risk age direction and the registry's.
Evidence that argues against this (1)
- The trial registry record and the protocol's own MRD publication both state the high-risk age criterion as under 6 months, the opposite direction to this abstract, so at least one of the two readily available descriptions of this trial's risk model is wrong. Stutterheim J et al. 2021
- E2established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper
The Interfant-99 primary report describes 482 infants aged 0-12 months treated with a hybrid ALL/AML protocol with 4-year event-free survival 47.0%, a negative randomised late-intensification question, and MLL rearrangement, very high white blood cell count, age under 6 months and poor prednisone response independently associated with inferior outcome.
A treatment protocol for infants younger than 1 year with acute lymphoblastic leukaemia (Interfant-99): an observational study and a multicentre randomised trial. · Pieters R, Schrappe M, De Lorenzo P, et al. · Lancet 2007What this evidence cannot show
Abstract only, for the same structural reason: pmcid null, isOpenAccess N, inEPMC N. The abstract states very high white blood cell count without a threshold, and whether the full text defines one is exactly what this beat could not check while investigating the origin of the 300 x10^9/L line.
Evidence that argues against this (1)
- Because the threshold question could not be checked in the full text, this beat's conclusion that no published derivation of the 300 x10^9/L cut-point exists is bounded by the sources it could read and is not a proof of absence. Pieters R et al. 2019
- E3strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
In Children's Oncology Group trial P9407 (209 infants analysed, 157 KMT2A-rearranged), applying Interfant-99 risk groups based on KMT2A rearrangement, age under 6 months and WBC above 300 x10^9/L gave 5-year event-free survival of 24% high risk versus 41% intermediate versus 69% KMT2A-germline (high versus intermediate P = .047), whereas a National Cancer Institute WBC cut of 50 x10^9/L gave 67% versus 29% within KMT2A-rearranged patients (P = .0002); the authors conclude that KMT2A-rearranged infants separate better by partner gene, by age at or below versus above 90 days, or by WBC below versus at or above 50 x10^9/L, and state that microarray separation of AFF1 cases at about 90 days provides biological grounds for the 90-day cut-off.
KMT2A partner genes in infant acute lymphoblastic leukemia have prognostic significance and correlate with age, white blood cell count, sex, and central nervous system involvement: a Children's Oncology Group P9407 trial study. · Robinson BW, Kairalla JA, Devidas M, et al. · Haematologica 2023What this evidence cannot show
Read in full text from haematologica.org after the Europe PMC core record returned pmcid null and PubMed returned an empty abstract, making all four PMC routes structurally unavailable. A Letter to the Editor, so the analysis is compressed and several results sit in supplementary figures not retrieved. P9407 ran 1996-2006 with era-appropriate partner assignment and 7.6% unknown partners. Both risk groupings are applied retrospectively to a cohort treated on neither, so the comparison measures discrimination and not the effect of allocation. This entry previously recorded this paper as title-only and unreadable; that was wrong and is corrected here.
Evidence that argues against this (2)
- The Interfant grouping is a three-variable conjunction and the NCI grouping is a single variable, so the smaller Interfant high-risk group has wider intervals and a weaker P value for reasons independent of where the WBC line sits; the head-to-head is not a clean test of 300 against 50. Leung AWK et al. 2024
- The paper's strongest discriminator was neither WBC cut-point but the partner gene (adjusted hazard ratios 2.51 for AFF1 and 3.30 for MLLT1 against KMT2A-germline, with MLLT3 indistinguishable from germline), so its message argues against optimising the count rather than for a particular value of it. Robinson BW et al. 2023
- E4moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
Searching PubMed on 2026-09-20 with infant terms, KMT2A or MLL, residual disease terms and every sequencing term (next-generation sequencing, high-throughput sequencing, clonoSEQ, immunosequencing) returns 2 records, of which one is a partner-gene discovery study and the other a targeted NGS diagnostic assay paper; searching infant terms with leukemia and clonoSEQ returns 1 record, a single case report.
PubMed E-utilities esearch, queries and counts recorded in this entry · National Center for Biotechnology Information · NCBI Entrez Programming Utilities 2026What this evidence cannot show
A counted absence is only as good as its symbol and phrase set. These queries use both the current symbol KMT2A and the retired symbol MLL, both minimal and measurable spellings of residual disease, and the vendor brand name clonoSEQ, but do not cover conference abstracts, which PubMed does not index, nor vendor registries. Title-checking was applied to every returned record.
Evidence that argues against this (1)
- The single infant clonoSEQ record is itself substantive - it tracks three dominant IGH/IGL sequences across diagnostic B-ALL, lineage-switched AML and post-transplant relapse - so the absence is of cohort studies, not of relevant observations, and a reader taking the count alone would under-rate the literature. Du J et al. 2021
- E5moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper
A targeted next-generation sequencing study using anchored multiplex PCR identified three novel KMT2A partner genes in childhood acute leukaemia and states that the resulting characterisations allow tracing the dynamics of minimal residual disease in those patients, without reporting MRD measurements.
BTK, NUTM2A, and PRPF19 Are Novel KMT2A Partner Genes in Childhood Acute Leukemia. · Zerkalenkova E, Lebedeva S, Borkovskaia A, et al. · Biomedicines 2021What this evidence cannot show
Three patients; the MRD statement describes what the characterisation enables. Recorded here as a bounded rejection - found, looks on-beat from the title and abstract, and is a target-discovery paper rather than an MRD study.
Evidence that argues against this (1)
- The distinction between target discovery and MRD measurement is a judgement: a paper that establishes a patient-specific target is a necessary step in the MRD workflow, and a future reader may reasonably want it counted as part of the MRD literature. Meyer C et al. 2023
- related to →MRD by genomic breakpoint: the only assay in this disease that is fusion-specific by construction
the enumeration this beat's assay entries came from
the counted absence of sequencing-based MRD cohorts in infants
three on-beat papers with no PMCID and no free route to the text
the threshold's origin is in the two documents this beat could not read
the risk-model discrepancy that the unreadable primary report would settle