The Ubiquitin Specific Peptidase 42 Gene (USP42) Is Recurrently Involved as a Fusion Gene with RUNX1 in Acute Myeloid Leukemia with the t(7;21)(p22;q22) Cryptic Translocation.
Bibliographic record
Abstract
Abstract The RUNX1 gene encodes the DNA-binding subunit of the heterodimeric transcription factor core binding factor (CBF) and is involved in the regulation of several genes important for hematopoiesis. RUNX1 is frequently rearranged by chromosomal translocations in a spectrum of hematologic malignancies, generating a RUNX1 fusion gene. Some of these RUNX1 fusion genes have been shown to be important in leukemogenesis, such as the ETV6/RUNX1 fusion in B-lineage acute lymphoblastic leukemia and the RUNX1/RUNX1T1 fusion in M2 acute myeloid leukemia (AML). We here describe the first case of adult AML with the t(7;21)(p22;q22) cryptic translocation. Morphologic analysis showed an AML without maturation (AML M1). The karyotype was 46, XY, del(5)(q22q33),?del(21)(q22) in twenty metaphases and analysis by spectral karyotyping (SKY) revealed a t(7;21). The translocation breakpoints at bands 21q22 and 7p22 were studied using bacterial artificial chromosomes (BACs) and showed RUNX1 and USP42 rearrangements. An in-frame fusion between RUNX1 exon 7 and USP42 exon 3 was confirmed by RT-PCR and sequencing. The RUNX1/USP42 fusion includes both the DNA binding RUNT domain of RUNX1 and the catalytic region of USP42. The RUNX1/USP42 fusion gene has recently been reported in one case of pediatric AML-M0 with normal karyotype at diagnosis (Paulsson et al., Leukemia2006;20:224). A complex karyotype including a deletion of the long arm of chromosome 5 was found at relapse in this case. Interestingly, blast cells in our t(7;21) positive leukemia share similar features with the previously published case. By flow cytometry, leukemic cells were positive for HLA-DR, CD34, CD33, CD13 markers and aberrantly expressed CD7 and CD56 without B-lineage markers. We next analyzed samples of CD7 and CD56 positive AMLs with different karyotypes (normal and complex) by FISH using probes to detect the RUNX1/USP42 fusion gene. The USP42 gene encodes a cysteine protease involved in the ubiquitin pathway as a deubiquitinating enzyme. Ubiquitin-specific proteases (USPs) are a large group of enzymes with highly conserved amino acid sequences that form the catalytic region. Some USPs have been shown to be involved in the stabilization of proteins, such as p53, and in the regulation of gene silencing. USP42 is part of a novel class of genes involved in the pathogenesis of leukemia and its role in hematologic cancers remains to be studied. To elucidate the possible implication of USP42 in hematologic malignancies, the expression of USP42 was also investigated by real-time PCR in our case with t(7;21) and in a series of acute leukemias.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| 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".