On Sunday 3rd April 2017, at the 107th American Association for Cancer Research (AACR) annual meeting in Washington, DC, USA, there was a poster session focused on the “Genomic Landscape of Lymphoma, Leukemia, and Lung, Bladder, and Other Cancers”.
In this study, the authors performed a whole-exome and targeted sequencing on eighty-five Partial Tandem Duplication of Mixed-lineage Leukemia Gene (MLL-PTD) Acute Myeloid Leukemia (AML) patients.
The key results were:
- Oncogenic driver mutations were identified in 90% of MLL-PTD patients
- DNMT3A (25%), IDH1/2 (31%), TET1 (5%), and TET2 (16.3%) were the most frequent mutations associated with MLL-PTD
- 67.5% of MLL-PTD patients had extensive mutations in proliferation-related pathways, most notably FLT3 mutations
- MLL-PTD patients (26%) had more frequent cohesin pathway mutations compared to AML samples from The Cancer Genome Atlas (TCGA) (13%, P = 0.01) or meta-analysis of 1,000 AMLs (9.1%, P = 0.001)
- A high proportion of the mutations in MLL-PTD patients had a strong tendency to disrupt the coding sequence in STAG2 compared to AML samples from TCGA; 16% vs 3%, P = 0.01
- MLL-PTD AML patients had alterations in the RNA processing pathway including mutations in U2AF1
- Sequential multiple mutations co-occur with MLL-PTD; IDH2/DNMT3A/U2AF1/TET2→MLL-PTD→RAS-receptor tyrosine kinase
The authors concluded by stating that “MLL-PTD is acquired after those remission-persisting, initiating mutations (IDH2, DNMT3A, TET2 and U2AF1), but prior to lesions of the proliferation-related drivers”.