IndraLab

Statements

USP2 binds KMT2A. 45 / 45
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"This issue commonly arises in KMT2A-USP2 fusion, involving a short inversion within the 11q23 region."
40361241
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"Fusion-driven primary subtypes of AML identified (n=3) were: RUNX1::RUNX1T1 , KMT2Ar ( KMT2A::MLLT1, KMT2A::MLLT10; KMT2A:USP2 ), and NUP98::NSD1 (Table 1; xref )."
39416119
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"In a previously published study of a cohort of 11 pediatric B-ALL patients with the KMT2A-USP2 fusion, three patients presented with central nervous system disease and 8 patients had positive-minimal residual disease at day 33, suggesting a poor prognosis of patients carrying this fusion ( xref )."
35087776
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"LAMP5 expression effectively predicted the infrequent gene fusion KMT2A-USP2, frequently overlooked by routine methods, and the resultant gene product may serve as a viable therapeutic target in KMT2A-r leukemia."
40361241
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"Our results identifying GATA2 as a potentially novel target of the KMT2A-USP2 fusion might provide novel clues for understanding the function of this fusion."
35087776
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"In other cases, clinical break-apart FISH assays only identified one component of the likely fusion ( NUP98 in sample 0158 and KMT2A in sample 0172), while the partner gene with prognostic significance was only identified after nanopore sequencing, ( NUP98 :: NSD1 and KMT2A::USP2 )."
39416119
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"Our data showed that in addition to the trans-activation of GATA2 by the KMT2A-USP2 fusion, a cis-activating mechanism is also involved in GATA2 dysregulation."
35087776
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"MPAL with KMT2A usually has a B/myeloid immunophenotype (an example case of MPAL with KMT2A::USP2 fusion, B/myeloid (bilineal, pattern 1b, in xref )), although other immunophenotypic variants, including rare cases of AUL and T/myeloid MPAL, have been reported [ xref , xref , xref ]."
40075717
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"Of importance, high expression levels of LAMP5 estimated the occurrence of all KMT2A-USP2 fusions."
35734412
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"As expected, the two samples with out-of-frame did not present a similar expression profile of the other KMT2A fusions, as well as one sample with KMT2A-USP2 , which had higher expression of NEDD4 and lower expression of SKIDA1 , HOXA9 and MEIS1 ( xref )."
35734412
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"The KMT2A fluorescence in situ hybridization (FISH) break-apart probe is widely used in clinical laboratories to detect KMT2A rearrangements because this gene has numerous fusion partners, but this approach has limitations, including the inability to detect cryptic fusions, such as KMT2A::USP2 [ xref ], or insertions [ xref , xref ], or partial tandem duplication [ xref ], and FISH also does not provide information regarding specific fusion partners."
40149468
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"It is important to highlight that the validation cohort contains three B-ALL patients with KMT2A-USP2 ."
35734412
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"Of note, LAMP5 was extremely overexpressed in these patients (the median FPKM was 122.13, 0.15, 33.25, for KMT2A-USP2 , KMT2A -WT, and other molecular subgroups, respectively), thus allowing the prediction of this gene fusion in all cases."
35734412
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"For instance, KMT2A-USP2 fusions are derived from an inversion within 11q23, and FISH is able to indicate KMT2A -r only for those cases accompanied by 3′ KMT2A deletion."
35734412
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"In this work, we observed that CSPG4 expression was unable to predict all KMT2A-USP2 fusions in B-ALL."
35734412
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"SKIDA1 expression may predict those rearrangements in most subtypes of acute leukemia, while LAMP5 presents good performance to point out KMT2A -r in B-ALL and ALAL, including the KMT2A-USP2 fusion."
35734412
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"As a highlight, LAMP5 expression was able to predict even the rare gene fusion KMT2A-USP2 , which is often missed by routine methods, and that gene product also appears to be a potential treatment target in KMT2A -r leukemia."
35734412
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"The incidences of KMT2A-MLLT1 (0.6%), KMT2A-ELL (0.4%), KMT2A-MLLT6 (0.2%), and KMT2A-USP2 (0.2%) were all below 1%."
34135310
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"The power of NARASIMHA lies in the fact that we can detect CGF that are challenging for conventional techniques, such as BCR–ABL1 -like ALL, B-other BCP-ALL, KMT2A -rearranged malignancies as well as cryptic lesions that will be missed by FISH (for e.g., NUP98–NSD1 , DUX4 rearrangements, KMT2A-USP2 fusions)."
32372024
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"This UMAP location prompted us to further examine these four undetermined cases and we found that all of them contained KMT2A::USP2 fusions."
38810562
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"In addition, the correlation between KMT2A-USP2 fusion and GATA2 activation not only indicates a potential trans-activating mechanism of GATA2 but also suggests that GATA2 is a target of KMT2A-USP2."
35087776
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"Further checking confirmed that these patients were the only two carrying this fusion in the cohort analyzed ( xref ), indicating that GATA2 could be trans-activated by KMT2A-USP2."
35087776
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"In other cases, clinical break-apart FISH assays only identified one component of the likely fusion ( NUP98 in sample 0158 and KMT2A in sample 0172), while the partner gene with prognostic significance was only identified after nanopore sequencing, ( NUP98 :: NSD1 and KMT2A::USP2 )."
40128561
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"In a prospective study, Meyer et al ( xref ) reported that a very small number of patients with acute leukemia have rearranged USP2 and USP8 genes and that the conserved region of the deubiquitinating enzyme ‘UCH-domain’ fuses to an extended 5´-MLL portion, which formed the fusion proteins MLL-USP2 and MLL-USP8."
37594087
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"Deubiquitination of USP2 stabilizes MDM protein and indirectly enhances the degradation of p53, which may be an important mechanism affecting the development of MLL-USP2 type leukemia."
37594087
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"Fusion-driven genomic subtypes of AML identified ( n  = 3) were: RUNX1::RUNX1T1 , KMT2Ar ( KMT2A::MLLT1, KMT2A::MLLT10; KMT2A:USP2 ), and NUP98::NSD1 (Table  xref and Supplementary Table  xref )."
40128561
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"Two of the patients ( KMT2A-CT45A1 , KMT2A-CLTC ) were not detected by multiplex RT–PCR, and 1 patient ( KMT2A-USP2 ) was undetectable by both FISH and multiplex RT–PCR."
35933338
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"All 48 detectable cases of KMT2A r transcript results were confirmed by split RT–PCR, which included 24 (50.00%) patients with KMT2A-AFF1 transcripts, 13 (27.08%) patients with KMT2A-MLLT3 transcripts , 5 (10.42%) patients with KMT2A-MLLT1 transcripts, and 1 (2.08%) patient with KMT2A-EPS15 , KMT2A-MLLT10 , KMT2A-FLNA , KMT2A-CLTC , KMT2A-CT45A1 or KMT2A-USP2 transcripts (Table xref )."
35933338
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"Rare fusion genes were detected by RNA-seq, including 1 case of KMT2A-USP2 , 4 cases of Ph-like related fusion genes, 5 cases of MEF2D rearrangement, 5 cases of PAX5 rearrangement, 3 cases of ZNF384 rearrangement, as well as several fusion genes whose significance were not clear or had not been reported in children with leukemia."
36476892
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"Notably, we found that both patients carried the same KMT2A-USP2 fusion."
35087776
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"Another 6 KMT2A fusions ( KMT2A-MLLT11 , KMT2A-SEPT5 , KMT2A-SEPT6 , KMT2A-MAML2 , KMT2A-MYO1F , KMT2A-USP2 ) fusions were detected in 1 case each."
34135310
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"These fusion genes comprised KMT2A::MLLT10 ( n  = 9) but also KMT2A::MLLT4 ( n  = 1; case 42), KMT2A::USP2 ( n  = 1; case 114) and KMT2A::SEPT6 ( n  = 1; case 110)."
38086945
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"[Two cases of refractory childhood acute B-lymphoblastic leukemia with positive KMT2A-USP2 treated with Belintouximab]."
37803862
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"Uncommon KMT2A r transcripts were determined in 3 patients in the cohort by RNAseq, and we believe that KMT2A-CT45A1, KMT2A-CLTC it and KMT2A-USP2 transcripts were the 1 st reported in the Chinese population."
35933338
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"Other studies indicated that the number of MLL–USP2 fusions was underestimated, mainly because of the use of techniques that detect rearrangements occurring in the MLL breakpoint cluster region (BRC-1) only, although most translocations occur outside that area [ xref , xref ]."
32139316
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"According to this study, a customized PCR panel was developed for MLL-r evaluation in 109 pediatric patients and MLL-USP2 translocations were present in ~15% of all rearrangements [ xref , xref ]."
32139316
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"Although the clinical outcome associated with this rearrangement remains unknown, and given the ability of DUBs to impede protein degradation, a MLL–USP2 chimeric protein has been proposed to drive leukemogenesis through USP2-mediated stabilization of the MLL1/MLL complex and/or by USP2-mediated stabilization of its substrates, specifically cyclin D1 [ xref ]."
32139316
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"Another 3 KMT2A fusions ( KMT2A-MLLT10 , KMT2A-USP2 , KMT2A-CARS ) were detected in 1 case each."
34135310
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"KMT2A-USP2 is a relatively rare type of KMT2A rearrangement and was recently reported as a recurrent fusion in pediatric B-ALL ( xref )."
35087776
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"Notably, GATA2 outlier expression was found in patients with the KMT2A-USP2 fusion but not in other KMT2A rearranged patients with high expression of wild-type USP2 ( xref ), suggesting that GATA2 transcription was activated by the chimeric fusion protein as a whole."
35087776
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"Specifically, four KMT2A fusion genes were identified: KMT2A-CTNND1 , KMT2A-MLLT3 , KMT2A-SEPT9 , and KMT2A-USP2 ."
41446535
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"Although patient SJINF066 was an infant (9-month-old) and SJBALL021549_D1 was a 9-year-old child, the expression levels of GATA2 in these two cases were comparable, indicating that trans-activation of GATA2 by KMT2A-USP2 is not influenced by age but rather by the function of this fusion."
35087776
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"The biological function of KMT2A-USP2 in ALL is still unclear."
35087776
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"However, we noticed that high expression of wild-type USP2 did not result in aberrant GATA2 transcription ( xref ), indicating that both parts of the KMT2A-USP2 fusion protein contribute to GATA2 activation."
35087776
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"Considering that the KMT2A fusion trans-activates HOX genes by directly binding to HOX loci ( xref ) and that histone H2A ubiquitination plays a critical function in polycomb-mediated transcriptional repression ( xref , xref ), it is likely that USP2 is relocated to the nucleus by the KMT2A-USP2 fusion and contributes to trans-activation of GATA2 transcription through deubiquitinating H2A and further disrupting gene silencing maintained by polycomb group complexes."
35087776