An intronic deletion in megakaryoblastic leukemia 1 is associated with hyperproliferation of B cells in triplets with Hodgkin lymphoma.

An intronic deletion in megakaryoblastic leukemia 1 is associated with hyperproliferation of B cells in triplets with Hodgkin lymphoma. Haematologica. 2019 Oct 03;: Authors: Record J, Sendel A, Kritikou JS, Kuznetsov NV, Brauner H, He M, Nagy N, Oliveira MMS, Griseti E, Haase CB, Dahlström J, Boddul S, Wermeling F, Thrasher AJ, Liu C, Andersson J, Claesson HE, Winqvist O, Burns SO, Björkholm M, Westerberg LS Abstract Megakaryoblastic leukemia 1 (MKL1) is a coactivator of serum response factor and together regulate transcription of actin cytoskeleton genes. MKL1 is associated with hematologic malignancies and immunodeficiency, but its role in B cells is unexplored. Here we examined B cells from monozygotic triplets with an intronic deletion in MKL1, two of whom were previously treated for Hodgkin lymphoma. To investigate MKL1 and B cell responses in HL pathogenesis, we generated Epstein Barr virus-transformed lymphoblastoid cell lines from the triplets and two controls. While cells from the Hodgkin lymphoma treated patients had a phenotype close to healthy controls, cells from the undiagnosed triplet had increased MKL1 mRNA, increased MKL1 protein, and elevated expression of MKL1-dependent genes. This was associated with elevated actin content, increased cell spreading, decreased expression of CD11a integrin molecules, and delayed aggregation. Moreover, cells from the undiagnosed triplet proliferated faster, displayed a higher propo...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research