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Journal of Pediatric Biochemistry 2015; 05(04): 146-156
DOI: 10.1055/s-0036-1572421
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Molecular Pathways in Childhood Acute Lymphoblastic Leukemia: From the Bench to the Bedside

Paola Bonaccorso
1   Cytogenetic and Molecular Biology Lab, Center of Pediatric Hematology Oncology, Azienda Policlinico–OVE, University of Catania, Catania, Italy
,
Nellina Andriano
1   Cytogenetic and Molecular Biology Lab, Center of Pediatric Hematology Oncology, Azienda Policlinico–OVE, University of Catania, Catania, Italy
2   Department of Medical and Experimental Medicine, University of Catania, Catania, Italy
,
Valeria Iachelli
1   Cytogenetic and Molecular Biology Lab, Center of Pediatric Hematology Oncology, Azienda Policlinico–OVE, University of Catania, Catania, Italy
2   Department of Medical and Experimental Medicine, University of Catania, Catania, Italy
,
Manuela La Rosa
1   Cytogenetic and Molecular Biology Lab, Center of Pediatric Hematology Oncology, Azienda Policlinico–OVE, University of Catania, Catania, Italy
2   Department of Medical and Experimental Medicine, University of Catania, Catania, Italy
,
Piera Samperi
3   Center of Pediatric Hematology Oncology, Azienda Policlinico–OVE, University of Catania, Catania, Italy
,
Emanuela Cannata
2   Department of Medical and Experimental Medicine, University of Catania, Catania, Italy
3   Center of Pediatric Hematology Oncology, Azienda Policlinico–OVE, University of Catania, Catania, Italy
,
Laura Lo Valvo
2   Department of Medical and Experimental Medicine, University of Catania, Catania, Italy
3   Center of Pediatric Hematology Oncology, Azienda Policlinico–OVE, University of Catania, Catania, Italy
,
Milena La Spina
3   Center of Pediatric Hematology Oncology, Azienda Policlinico–OVE, University of Catania, Catania, Italy
,
Andrea Di Cataldo
2   Department of Medical and Experimental Medicine, University of Catania, Catania, Italy
3   Center of Pediatric Hematology Oncology, Azienda Policlinico–OVE, University of Catania, Catania, Italy
,
Giovanna Russo
2   Department of Medical and Experimental Medicine, University of Catania, Catania, Italy
3   Center of Pediatric Hematology Oncology, Azienda Policlinico–OVE, University of Catania, Catania, Italy
,
Luca Lo Nigro
1   Cytogenetic and Molecular Biology Lab, Center of Pediatric Hematology Oncology, Azienda Policlinico–OVE, University of Catania, Catania, Italy
3   Center of Pediatric Hematology Oncology, Azienda Policlinico–OVE, University of Catania, Catania, Italy
› Author Affiliations
Further Information

Publication History

16 December 2015

28 December 2015

Publication Date:
19 February 2016 (online)

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Abstract

Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood, originating from a neoplastic deviation of B or T lymphocyte. Cytogenetic, cytofluorimetric, and genomic analyses clearly defined several subtypes of ALL. However, the leukemogenic process is characterized by different pathways' alteration which are still to be determined, in the attempt to identify specific targets to be druggable. In this review, we explore the main molecular pathways, which are commonly shared between different subtypes of pediatric ALL. These cell-signaling pathways affect many functions, including cell proliferation, apoptosis, migration, and differentiation. The PI3K/AKT/mTOR pathway is one of the most studied, with higher expected promises of being targetable. RAS pathway is also widely studied in all types of cancer. The Wnt/Beta catenin has been recently studied in ALL. Finally, CXCL12/CXCL4 axis has a crucial role in regulating hematopoietic stem cell and bone marrow niche. The complete characterization of these pathways will allow us to design a specific patient–disease profile associated with a tailored treatment, with the highest grade of efficacy and the lowest grade of toxicity.

Keywords

RAS - PI3K/AKT/mTOR - Wnt-Beta catenin - CXCL12 - childhood - ALL
 

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