Gene-expression patterns in relapsed B-cell acute lymphoblastic leukemia and potential therapeutic targets


ERBİLGİN Y. , İşlek B., Firtina S., HATIRNAZ NG Ö. , İnal A., Doğan P., ...More

European Society of Human Genetics 2016 (ESHG2016, Avrupa Genetik Kongresi 2016), Barselona, Spain, 21 - 24 May 2016, pp.678

  • Publication Type: Conference Paper / Full Text
  • City: Barselona
  • Country: Spain
  • Page Numbers: pp.678

Abstract

Introduction: Relapsed acute lymphoblastic leukemia (ALL) ranks as the fourth most common childhood malignancy. To identify targets for new therapies, a through understanding of the genetic lesions contributing to establishment of the leukemic clone and resistance to therapy is required. The goals of the study were to provide an explanation for the observed differences in outcome among patients who relapse early and to define highrisk patients much better. Materials and Methods: We examined gene-expression profiles in 20 childhood B-cell ALL and healthy B-cell subsets by using “Illumina HumanHT12 v4 Expression BeadChip” technology. According to the differential analysis, selected eight genes had been validated in a larger B-ALL cohort (n=81 patients) by using Quantitative Real-Time PCR. Results and Conclusions: Diagnose patients who had relapse showed differential expression in cell cycle, apoptosis, purine/pyrimidine metabolism, and different cancer pathways. Many of these pathways have been implicated in tumorgenesis previously and are attractive targets for intervention strategies. After the validation process, aberrant PMAIP1 and RASD1 expression had been linked with relapsed. PMAIP1 is related with ERK Signaling and apoptosis, RASD1 is related with MAPK targets. However, further studies are required to understand the impact of RASD1 and PMAIP1 genes in drug resistance in B-cell ALL. The study was supported by The Scientific and Technological Research Council of Turkey (TUBITAK Project Number:114S038), Istanbul University Scientific Research Project (IU. BAP Project Number: 11021), Istanbul Development Agency (ISTKA TR10/15/YNK/0093).