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J Cancer 2017; 8(19):4124. doi:10.7150/jca.21725 This issue Cite

Research Paper

T-cell Acute Lymphoblastic Leukemia Cells Display Activation of Different Survival Pathways

Sausan A. Moharram^1,2, Kinjal Shah^1,2, Julhash U. Kazi^1,2✉

1. Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund, Sweden;
2. Lund Stem Cell Center, Department of Laboratory Medicine, Lund University, Lund, Sweden.

✉ Corresponding author: Julhash U. Kazi (kazi.uddinlu.se), Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Medicon Village 404:C3, Scheelevägen 8, 22363 Lund, Sweden.

Abstract

T-cell acute lymphoblastic leukemia (T-ALL) is a disease of the blood affecting T-lymphocytes. Although notable improvements have been achieved in T-ALL treatment, half of the adult T-ALL patients still experience treatment failure. In order to develop a targeted therapy, we need a better understanding of T-ALL pathogenesis. In this study, we used patient-derived cell lines which display resistance to glucocorticoids. We observed that different cell lines are dependent on different survival signaling pathways. Aberrant activation of AKT, p38, S6K or ERK signaling was not found to the same degree in all cell lines studied. To understand the molecular differences in T-ALL cells, we compared gene expression and somatic mutations. Gene set enrichment analysis showed enrichment of the mTORC1, MAPK or TGF-beta signaling pathways. Loss-of-function mutations in the TP53 and FBXW7 genes were identified in all cell lines investigated. Thus, we suggest that T-ALL cells from different patients are addicted to different mutations and thereby to different signaling pathways. Therefore, understanding the enrichment of molecular pathways for each individual patient will provide us with a more precise and specific treatment plan.

Keywords: T-ALL, Lymphoblast, MOLT-3, Jurkat, CCRF-CEM.

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