Human iPSC-based model of severe congenital neutropenia reveals elevated UPR and DNA damage in CD34+ cells preceding leukemic transformation

Severe congenital neutropenia (CN) is a mono-lineage pre-leukemia bone marrow failure syndrome, characterized by early onset of neutropenia and severe infections owing to promyelocytic maturational arrest in the bone marrow [1,2]. CN is a heterogeneous disease caused by mutations in a number of genes, including ELANE [3] (most common [1]), HAX1 [4], CSF3R [5,6], JAGN1 [7], G6PC3 [8], TCIRG1 [9] and others. In most cases, ELANE mutations are missense mutations that are distributed throughout all five exons of the ELANE gene, although a majority of mutations are found in exons 4 and 5 [10].

Source: Experimental Hematology - January 4, 2019 Category: Hematology Authors: Benjamin Dannenmann, Azadeh Zahabi, Perihan Mir, Benedikt Oswald, Regine Bernhard, Maksim Klimiankou, Tatsuya Morishima, Cornelia Zeidler, Lothar Kanz, Nico Lachmann, Thomas Moritz, Karl Welte, Julia Skokowa Source Type: research