SOX7 promotes the maintenance and proliferation of B cell precursor acute lymphoblastic cells

// Sara Cuvertino 1, 4 , Genny Filiciotto 1 , Ashish Masurekar 2 , Vaskar Saha 2, 3 , Georges Lacaud 1 , Valerie Kouskoff 1 1 Cancer Research UK Manchester Institute, The University of Manchester, Manchester M20 4BX, UK 2 Children’s Cancer Group, Institute of Cancer Sciences, The University of Manchester, Manchester M20 4BX, UK 3 TCS Translational Cancer Research Centre, Tata Medical Centre, Kolkata 700156, India 4 Present address: Genetic Medicine, Institute of Human Development, University of Manchester, St Mary’s Hospital, Manchester M13 9WL, UK Correspondence to: Georges Lacaud, email: georges.lacaud@cruk.manchester.ac.uk Valerie Kouskoff, email: valerie.kouskoff@cruk.manchester.ac.uk Keywords: SOX7, leukemia, B-ALL Received: February 19, 2016 Accepted: June 17, 2016 Published: July 7, 2016 ABSTRACT B cell precursor acute lymphoblastic leukemia (BCP-ALL) is the most frequent type of cancer in children. Despite progresses in curative treatment, intensive chemotherapy regimens still cause life threatening complications. A better understanding of the molecular mechanisms underlying the emergence and maintenance of BCP-ALL is fundamental for the development of novel therapies. Here, we establish that SOX7 is frequently and specifically expressed in BCP-ALL and that the expression of this transcription factor does not correlate with any specific cytogenetic abnormalities. Using human leukemia model systems, we establish that the down-regulation of SOX7 in BCP-ALL causes a significant decrease in proliferation and clonogenicity in vitro that correlates with a delay in leukemia initiation and burden in vivo . Overall, these results identify a novel and important functional role for the transcription factor SOX7 in promoting the maintenance of BCP-ALL.