Next Article in Journal
Proton Partial Breast Irradiation: Detailed Description of Acute Clinico-Radiologic Effects
Next Article in Special Issue
Biomarkers for Early Diagnosis and Prognosis of Malignant Pleural Mesothelioma: The Quest Goes on
Previous Article in Journal
EBNA1: Oncogenic Activity, Immune Evasion and Biochemical Functions Provide Targets for Novel Therapeutic Strategies against Epstein-Barr Virus- Associated Cancers
Previous Article in Special Issue
Role of Pattern Recognition Receptors in KSHV Infection
Article Menu
Issue 4 (April) cover image

Export Article

Open AccessReview

New Challenges in Targeting Signaling Pathways in Acute Lymphoblastic Leukemia by NGS Approaches: An Update

1
IBSAL, IBMCC, Universidad de Salamanca-CSIC, Cancer Research Center, 37007 Salamanca, Spain
2
Escuela de Ciencias Biológicas, Grupo de investigación en Ciencias Biomédicas (GICBUPTC), Universidad Pedagógica y Tecnológica de Colombia, Tunja 150001, Colombia
3
Universidad de Salamanca-CSIC, Hospital Universitario de Salamanca, 37007 Salamanca, Spain
*
Author to whom correspondence should be addressed.
A.M., M.F.-C., R.B., J.M.H.-R. contributed equally to this work.
Cancers 2018, 10(4), 110; https://doi.org/10.3390/cancers10040110
Received: 2 March 2018 / Revised: 3 April 2018 / Accepted: 5 April 2018 / Published: 7 April 2018
(This article belongs to the Collection Cancer Biomarkers)
  |  
PDF [23433 KB, uploaded 3 May 2018]
  |  

Abstract

The identification and study of genetic alterations involved in various signaling pathways associated with the pathogenesis of acute lymphoblastic leukemia (ALL) and the application of recent next-generation sequencing (NGS) in the identification of these lesions not only broaden our understanding of the involvement of various genetic alterations in the pathogenesis of the disease but also identify new therapeutic targets for future clinical trials. The present review describes the main deletions, amplifications, sequence mutations, epigenetic lesions, and new structural DNA rearrangements detected by NGS in B-ALL and T-ALL and their clinical importance for therapeutic procedures. We reviewed the molecular basis of pathways including transcriptional regulation, lymphoid differentiation and development, TP53 and the cell cycle, RAS signaling, JAK/STAT, NOTCH, PI3K/AKT/mTOR, Wnt/β-catenin signaling, chromatin structure modifiers, and epigenetic regulators. The implementation of NGS strategies has enabled important mutated genes in each pathway, their associations with the genetic subtypes of ALL, and their outcomes, which will be described further. We also discuss classic and new cryptic DNA rearrangements in ALL identified by mRNA-seq strategies. Novel cooperative abnormalities in ALL could be key prognostic and/or predictive biomarkers for selecting the best frontline treatment and for developing therapies after the first relapse or refractory disease. View Full-Text
Keywords: NGS; mutations; fusion genes; pathways NGS; mutations; fusion genes; pathways
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Montaño, A.; Forero-Castro, M.; Marchena-Mendoza, D.; Benito, R.; Hernández-Rivas, J.M. New Challenges in Targeting Signaling Pathways in Acute Lymphoblastic Leukemia by NGS Approaches: An Update. Cancers 2018, 10, 110.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Cancers EISSN 2072-6694 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top