Transcriptional profiles of familial cases of myeloproliferative neoplams

ABSTRACT: Familial cases of MPN are usually transmitted by autosomal inheritance with incomplete penetrance, appear in adulthood, and demonstrate acquired genetic abnormalities that are similar to those identified in sporadic cases such as JAK2V617F and TET2 mutations. Linkage and segregation analyses indicate that genetic predisposition to MPN cannot be related to a common alteration and rather involves a number of susceptibility loci responsible for independent familial aggregations. Identification of these susceptibility loci may improve our understanding of the mechanisms of predisposition, which may result either in the induction of a genetic instability, favoring the acquisition of oncogenic mutations or corresponds to a fertile ground for selection of somatic mutations. Here, we describe a newly identified germline copy number variation (CNV) that predisposes to essential thrombocythemia (ET) which rapidly progress to myelofibrosis (MF) and MDS/AML. Using induced pluripotent stem and primary cells to explore hematopoietic differentiation, we demonstrate that overexpressed ATG2B and GSKIP enhance hematopoietic progenitor differentiation, including megakaryocytic through increasing their sensitivity to TPO. To evaluate the overexpression of ATG2B and GSKIP in patients and their role in hematopoiesis, we generated EBV cell lines from peripheral blood of patients or relatives. These cell lines were cultured in RPMI with 20% FBS. The present study concerns gene expression of EBV cell lines from patients and controls after RNA extraction (qiagen kit). Gene expression was performed in single color on Agilent8x60K v2 Human whole genome (design 039494) in replicates 15 cell lines from affected patients and 9 non affected controls).

ORGANISM(S): Homo sapiens

SUBMITTER: Dessen Philippe 

PROVIDER: E-MTAB-3570 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress