Overexpression of MEL1 as a Novel Fusion Partner of AML1 in the Blastic Phase of Chronic Myeloid Leukemia with the Recurrent Cryptic Translocation t(1;21)(p36.3;q22).
Bibliographic record
Abstract
Abstract Located at 1p36.3, MEL1 is a member of the MDS1/EVI1 gene family and encodes a zinc finger protein with a N-terminal PR-domain. It has been proposed that the overexpression of a modified version of MEL1 lacking the PR domain is oncogenic, whereas MEL1 retaining the PR domain is anti-tumorigenic. MEL1 is known to be overexpressed in some myeloid malignancies with reciprocal translocation t(1;3)(p36.3;q21) characterized by trilineage dysplasia and poor prognosis. It is suggested that the translocation of RPN1 gene at 3q21 in the vicinity of MEL1 gene might activate MEL1 expression through an enhancer element. Here we characterized a recurrent cryptic translocation t(1;21)(p36.3;q22) that fuses MEL1 to AML1 gene in a blastic transformation of chronic myeloid leukemia (CML). Fluorescence in situ hybridization (FISH) analysis with BAC/PAC clones revealed that the breakpoints are in intron 1 of MEL1 and between intron 1 and exon 8 of AML1. RT-PCR analysis showed that AML1-MEL1, but not the reciprocal MEL1-AML1 was expressed. Many splicing variants are present, and all fusions splice the 5′ end of AML1 that contains the RUNT domain with almost the entire MEL1. Furthermore two fusion transcripts contained open reading frames making possible the translation of two forms of AML1-MEL1 fusion proteins. To investigate if AML1-MEL1 leads to an inappropriate expression of MEL1 we performed a quantitative RT-PCR with primers outside and within the fused MEL1 allowing the detection of the normal and the rearranged allele respectively. Interestingly, our data show that while no normal MEL1 transcript was detected, there was an overexpression of the fused MEL1. These results suggest that similarly to AML1-EVI1 gene, overexpression of MEL1 could be regulated by the AML1 promoter in leukemic cells with the AML1-MEL1 fusion gene and might also play an important role in the progression of CML. Moreover, in contrast to previous studies showing an antioncogenic role for the PR domain, our findings indicate that in some leukemias, the overexpression of MEL1 is not restricted to the MEL1 PR-lacking form. This suggests that the mechanism by which the PR domain has his effect, is more complex than previously thought.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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".