KMT2E-ASNS: a novel relapse-specific fusion gene in early T-cell precursor acute lymphoblastic leukemia
Bibliographic record
Abstract
2][3] This heterogeneous subgroup shows a distinctive immature immunophenotype characterized by the differential expression of cell surface markers during T-cell development. 2,4][9] ETP-ALLs are associated with multiple rearrangements affecting gene-coding regions, quite possibly with a bearing on the formation of novel chimeric fusion genes, 2,4,10,11 for which the clinical significance remains as yet largely unknown.In order to better understand the factors leading to childhood ETP-ALL relapse, the whole transcriptome of 2 ETP-ALL patients was investigated with a view toward identifying relapse-specific rearrangements.The 2 patients (TC0002 and TC0022) were diagnosed with ALL at 12 and 16 years of age, respectively, and immunophenotyping revealed antigenic determinants corresponding to ETP-ALL subtype.Both of them were classified as high risk and treated with an L-asparaginase- intensive chemotherapy regimen, according to Dana-Farber Cancer Institute Childhood ALL Consortium protocol for high-risk patients.In both cases, the patients relapsed, after 5 and 2 years respectively, after having obtained an initial remission.The whole transcriptome analysis revealed a novel recurrent fusion transcript linking the 59 untranslated region (UTR) of KMT2E to the entire coding sequence of ASNS, indicating a promoter swap (Figure 1A-B).Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was performed at diagnosis, in conjunction with bone marrow samples taken at different time points after induction treatment of TC0002, and these indicated that the fusion was relapse specific (Figure 1C-D).This novel recurrent fusion may have been previously overlooked in other studies as a consequence of the rarity of transcriptome analysis having being performed on relapsed ETP-ALL, as this may indeed be the sole recorded study.KMT2E and ASNS are located ; 7.1 Mb apart on chromosome 7, in opposite orientations (supplemental Figure 1A, available on the Blood Web site), implying that the observed KMT2E-ASNS transcripts may be the result of a cryptic inversion [inv(7)(q22.3q21.3)].In spite of the absence of a reciprocal ASNS-KMT2E transcript, we observed a transcript linking the 59 portion of the MGC72080 pseudogene (located ;40 kb upstream of ASNS) to exon 2 of KMT2E in the relapse material of both of these patients, which supports the chromosomal inversion hypothesis (supplemental Figure 1B).To assess the impact of the promoter swap on ASNS expression, we measured the expression levels of KMT2E, ASNS, and KMT2E-ASNS
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.004 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".