Identification of KMT2A-ARHGEF12 fusion in a child with a high-grade B-cell lymphoma

IGH Rearrangement Evolution in Adult KMT2A-rearranged B-cell Precursor ALL: Implications for Cell-of-origin and MRD Monitoring

“…Strikingly, the only KMT2A rearranged case without any kind of clonal evolution harbored an atypical hitherto not described KMT2A::UBASH3B in‐frame gene fusion, which spans 4.3 Mbp on chromosome 11q, suggesting an interstitial deletion as a mechanism of origin (http://links.lww.com/HS/A331). A KMT2A gene fusion originating from interstitial deletion ( KMT2A::ARHGEF12 ) has been described in rare cases of therapy‐related AML and ALL as well as high‐grade B‐cell lymphoma identifying KMT2A deletions as driver mechanism in very specific circumstances 12 . The other 17 KMT2A rearranged cases showed typical KMT2A fusions ( KMT2A::AFF1 [16/18, 89%] or KMT2A::MLLT1 [1/18, 6%]) (http://links.lww.com/HS/A331).…”

“…A KMT2A gene fusion originating from interstitial deletion ( KMT2A::ARHGEF12 ) has been described in rare cases of therapy-related AML and ALL as well as high-grade B-cell lymphoma identifying KMT2A deletions as driver mechanism in very specific circumstances. 12 The other 17 KMT2A rearranged cases showed typical KMT2A fusions ( KMT2A::AFF1 [16/18, 89%] or KMT2A::MLLT1 [1/18, 6%]) (Suppl. Table S1A).…”

Interaction kinetics between p115-RhoGEF and Gα13 are determined by unique molecular interactions affecting agonist sensitivity

“…Several diseases have been associated with the misregulation of RH-RhoGEFs, such as arterial hypertension 18 – 21 , ischemic heart disease 22 , cardiac infarction 23 , cardiac hypertrophy 20 , 24 , proliferation defects 25 – 27 , inflammation 28 , 29 and several forms of cancer 30 – 40 . Therefore, additional insight into the Gα 12/13 -RH-RhoGEF interaction, which in turn gives more insight into the RhoA signaling cascade as a whole, may prove beneficial to combat the aforementioned diseases.…”