Efficacy of combined CDK9/13ET inhibition in preclinical models of MLL-rearranged acute leukemia
Hannah McCalmont, Ka Leung Li, Luke Jones, John Toubia, Sarah C Bray, Debora A Casolari, Chelsea Mayoh, Saumya E Samaraweera, Ian D Lewis, Rab K Prinjha, Nicholas Smithers, Shudong Wang, Richard B Lock, Richard J D'Andrea
BLOOD ADVANCES | AMER SOC HEMATOLOGY | Published : 2020
Chromosomal rearrangements of the lysine methyltransferase 2A (KMT2A or MLL) gene are observed in ;10% of all acute leukemias, with particularly high frequency (;80%) in infant acute lymphoblastic leukemia (ALL),1 where, despite aggressive chemotherapy, patients still experience poor outcome and long-term side effects.2 Mixed lineage leukemia (MLL) rearrangements (MLL-r) also indicate particularly poor outcomes for patients with acute myeloid leukemia (AML).3 Mechanistically, MLL-r frequently generates fusion proteins involving partners that function in the super elongation complex,4 the result of which is aberrant recruitment to MLL target genes of the positive transcription elongation fact..View full abstract
Awarded by National Health and Medical Research Council ofAustralia (NHMRC)
Awarded by Tour deCure research grant
This work was supported by the National Health and Medical Research Council ofAustralia (NHMRC; fellowships APP1059804 and APP1157871 [R.B.L.], and NHMRC program grant APP1091261 [R.B.L.]), a Tour deCure research grant (17-UNSW-RS-01) (R.B.L. and R.J.D.), grants from the Ray and Shirl Norman Foundation, the Royal Adelaide HospitalResearch Foundation, theContributing Hematologist Committee (R.J.D., I.D.L., andS.W.), and an Industry Development grant from Bioinnovation SA (R.J.D. and S.W.).