Evolutionary and immune microenvironment dynamics during neoadjuvant treatment of oesophagael adenocarcinoma.

Locally advanced oesophageal adenocarcinoma (EAC) remains difficult to treat because of common resistance to neoadjuvant therapy and high recurrence rates. The ecological and evolutionary dynamics responsible for treatment failure are incompletely understood. Here, we performed a comprehensive multi-omic analysis of samples collected from EAC patients in the MEMORI clinical trial, revealing major changes in gene expression profiles and immune microenvironment composition that did not appear to be driven by changes in clonal composition.

Activating CBL mutations are associated with a distinct MDS/MPN phenotype.

Activating point mutations in CBL have recently been identified in diverse subtypes of myeloid neoplasms. Because detailed clinical and hematological characteristics of CBL-mutated cases is lacking, we screened 156 BCR-ABL and JAK2 V617F negative patients with myeloproliferative neoplasms (MPN) and overlap syndromes between myelodysplastic syndrome (MDS) and MPN (MPS/MPN) for mutations in exons 8 and 9 of CBL by denaturing high-performance liquid chromatography and direct sequencing. CBL mutations were identified in 16/156 patients (10%), of which five also carried mutations in EZH2 (n = 3) and TET2 (n = 2).

SNP array analysis of tyrosine kinase inhibitor-resistant chronic myeloid leukemia identifies heterogeneous secondary genomic alterations.

To elucidate whether tyrosine kinase inhibitor (TKI) resistance in chronic myeloid leukemia is associated with characteristic genomic alterations, we analyzed DNA samples from 45 TKI-resistant chronic myeloid leukemia patients with 250K single nucleotide polymorphism arrays. From 20 patients, matched serial samples of pretreatment and TKI resistance time points were available. Eleven of the 45 TKI-resistant patients had mutations of BCR-ABL1, including 2 T315I mutations.

Prognostic implications of NOTCH1 and FBXW7 mutations in adult acute T-lymphoblastic leukemia.

Background: NOTCH1 mutations have been associated with a favorable outcome in pediatric acute T-lymphoblastic leukemia. However, the results of studies on the prognostic significance of NOTCH1 mutations in adult T-lymphoblastic leukemia remain controversial.

Design And Methods: Here we have investigated the prognostic impact of mutations in the NOTCH1 pathway, in particular, the NOTCH1 and FBXW7 genes, in a large cohort of adult patients with T-lymphoblastic leukemia (n=126).

Epigenetic control of differential expression of specific ERG isoforms in acute T-lymphoblastic leukemia.

Expression of ERG is of prognostic significance in acute myeloid leukemia (AML) and T-lymphoblastic leukemia (T-ALL) pointing to its role in leukemogenesis. To unravel its transcriptional regulation we analyzed the expression of ERG specific isoforms. Expression of the two main isoforms ERG2 and ERG3 was found in AML and normal CD34+ cells, whereas T-ALL blasts only expressed ERG isoforms harboring exon 5 (ERG3) lacking expression of ERG2.