Clinical features and gene-and microRNA-expression patterns in adult acute leukemia patients with t(11;19)(q23;p13.1) and t(11;19)(q23;p13.3)

Translocations involving the KMT2A (MLL) gene, located at 11q23, and two different partner genes, ELL and MLLT1, located at 19p13.1 and 19p13.3, respectively, have been reported in both acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).1, 2 However, there are limited data describing clinical and molecular differences between adult patients with t(11;19)(q23;p13.1) and those with t(11;19)(q23;p13.3). Neither the Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer3 nor large studies correlating chromosome abnormalities with clinical outcome4 distinguish the two types of t(11;19); instead they combine both into one cytogenetic group

EGR2 mutations define a new clinically aggressive subgroup of chronic lymphocytic leukemia

Recurrent mutations within EGR2 were recently reported in advanced-stage chronic lymphocytic leukemia (CLL) patients and associated with a worse outcome. To study their prognostic impact, 2403 CLL patients were examined for mutations in the EGR2 hotspot region including a screening (n=1283) and two validation cohorts (UK CLL4 trial patients, n=366; CLL Research Consortium (CRC) patients, n=490). Targeted deep-sequencing of 27 known/postulated CLL driver genes was also performed in 38 EGR2-mutated patients to assess concurrent mutations. EGR2 mutations were detected in 91/2403 (3.8%) investigated cases, and associated with younger age at diagnosis, advanced clinical stage, high CD38 expression and unmutated IGHV genes. EGR2-mutated patients frequently carried ATM lesions (42%), TP53 aberrations (18%) and NOTCH1/FBXW7 mutations (16%). EGR2 mutations independently predicted shorter time-to-first-treatment (TTFT) and overall survival (OS) in the screening cohort; they were confirmed associated with reduced TTFT and OS in the CRC cohort and independently predicted short OS from randomization in the UK CLL4 cohort. A particularly dismal outcome was observed among EGR2-mutated patients who also carried TP53 aberrations. In summary, EGR2 mutations were independently associated with an unfavorable prognosis, comparable to CLL patients carrying TP53 aberrations, suggesting that EGR2-mutated patients represent a new patient subgroup with very poor outcome. © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved