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T-cell acute lymphoblastic leukemia cells display activation of different survival pathways

Moharram, Sausan A. LU ; Shah, Kinjal LU and Kazi, Julhash U. LU (2017) In Journal of Cancer 8(19). p.4124-4129
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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
CCRF-CEM, Jurkat, Lymphoblast, MOLT-3, T-ALL
in
Journal of Cancer
volume
8
issue
19
pages
6 pages
publisher
Hindawi Publishing Corporation
external identifiers
  • scopus:85035048419
  • wos:000418498600024
ISSN
2090-2905
DOI
10.7150/jca.21725
language
English
LU publication?
yes
id
a5770d3e-c44c-480e-a012-c59773870d09
date added to LUP
2017-12-21 16:36:43
date last changed
2018-03-23 03:00:10
@article{a5770d3e-c44c-480e-a012-c59773870d09,
  abstract     = {<p>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.</p>},
  author       = {Moharram, Sausan A. and Shah, Kinjal and Kazi, Julhash U.},
  issn         = {2090-2905},
  keyword      = {CCRF-CEM,Jurkat,Lymphoblast,MOLT-3,T-ALL},
  language     = {eng},
  number       = {19},
  pages        = {4124--4129},
  publisher    = {Hindawi Publishing Corporation},
  series       = {Journal of Cancer},
  title        = {T-cell acute lymphoblastic leukemia cells display activation of different survival pathways},
  url          = {http://dx.doi.org/10.7150/jca.21725},
  volume       = {8},
  year         = {2017},
}