Aline Massé

TL;DR: Somatic mutations in TET2 occur in about 15% of patients with various myeloid cancers and were present in hematopoietic stem cells and preceded the JAK2 V617F mutation in the five samples from patients with myeloproliferative disorders that were analyzed.

TL;DR: OtX015 and JQ1 have similar biological effects in leukemic cells, supporting OTX015 evaluation in a Phase Ib trial in relapsed/refractory leukemia patients and Sequential combinations of OTx015 with other epigenetic modifying drugs, panobinostat and azacitidine have a synergic effect on growth of the KASUMI cell line.

TL;DR: The results suggest that, for PV, erythrocytosis can occur through two mechanisms: terminal erythroid amplification triggered by JAK2 617V>F homozygosity, and a 2-step process including the upstream amplification of heterozygous cells that may involve additional molecular events.

TL;DR: It is shown that the level of 5-hmC is decreased in granulocyte DNA from myeloproliferative neoplasm patients with TET2 mutations compared with granulocytes DNA from healthy patients, and inhibition of TET1 by RNA interference decreases 5-HMC levels in both human leukemia cell lines and cord blood CD34(+) cells, confirming the enzymatic function of Tet2 in human hematopoietic cells.

TL;DR: Results demonstrate that myeloproliferative disorders take their origin in a true myeloids/lymphoid progenitor cell but that their phenotype is related to a downstream selective proliferative advantage of the myeloid lineages.