Leukemia initiating cells (LICs) represent a reservoir that is believed to drive relapse and resistance to chemotherapy in blood malignant disorders. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive neoplastic disorder of immature hematopoietic precursors committed to the T-cell lineage. T-ALL comprises about 15% of pediatric and 25% of adult ALL cases and is prone to early relapse. Although the prognosis of T-ALL has improved especially in children due to the use of new intensified treatment protocols, the outcome of relapsed T-ALL cases is still poor. Putative LICs have been identified also in T-ALL. LICs are mostly quiescent and for this reason highly resistant to chemotherapy. Therefore, they evade treatment and give rise to disease relapse. At present great interest surrounds the development of targeted therapies against signaling networks aberrantly activated in LICs and important for their survival and drug-resistance. Both the Notch1 pathway and the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) network are involved in T-ALL LIC survival and drug-resistance and could be targeted by small molecules. Thus, Notch1 and PI3K/Akt/mTOR inhibitors are currently being developed for clinical use either as single agents or in combination with conventional chemotherapy for T-ALL patient treatment. In this review, we summarize the existing knowledge of the relevance of Notch1 and PI3K/Akt/mTOR signaling in T-ALL LICs and we examine the rationale for targeting these key signal transduction networks by means of selective pharmacological inhibitors.

Targeting Signaling Pathways in T-cell acute lymphoblastic leukemia initiating cells / Martelli, Am; Lonetti, A; Buontempo, F; Ricci, F; Tazzari, Pl; Evangelisti, C; Bressanin, D; Cappellini, A; Orsini, E; Chiarini, F. - In: ADVANCES IN BIOLOGICAL REGULATION. - ISSN 2212-4926. - 56:(2014), pp. 6-21. [10.1016/j.jbior.2014.04.004]

Targeting Signaling Pathways in T-cell acute lymphoblastic leukemia initiating cells

Chiarini F
2014

Abstract

Leukemia initiating cells (LICs) represent a reservoir that is believed to drive relapse and resistance to chemotherapy in blood malignant disorders. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive neoplastic disorder of immature hematopoietic precursors committed to the T-cell lineage. T-ALL comprises about 15% of pediatric and 25% of adult ALL cases and is prone to early relapse. Although the prognosis of T-ALL has improved especially in children due to the use of new intensified treatment protocols, the outcome of relapsed T-ALL cases is still poor. Putative LICs have been identified also in T-ALL. LICs are mostly quiescent and for this reason highly resistant to chemotherapy. Therefore, they evade treatment and give rise to disease relapse. At present great interest surrounds the development of targeted therapies against signaling networks aberrantly activated in LICs and important for their survival and drug-resistance. Both the Notch1 pathway and the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) network are involved in T-ALL LIC survival and drug-resistance and could be targeted by small molecules. Thus, Notch1 and PI3K/Akt/mTOR inhibitors are currently being developed for clinical use either as single agents or in combination with conventional chemotherapy for T-ALL patient treatment. In this review, we summarize the existing knowledge of the relevance of Notch1 and PI3K/Akt/mTOR signaling in T-ALL LICs and we examine the rationale for targeting these key signal transduction networks by means of selective pharmacological inhibitors.
2014
Advances in Biological Regulation vol. 55
Elsevier Ltd
Targeting Signaling Pathways in T-cell acute lymphoblastic leukemia initiating cells / Martelli, Am; Lonetti, A; Buontempo, F; Ricci, F; Tazzari, Pl; Evangelisti, C; Bressanin, D; Cappellini, A; Orsini, E; Chiarini, F. - In: ADVANCES IN BIOLOGICAL REGULATION. - ISSN 2212-4926. - 56:(2014), pp. 6-21. [10.1016/j.jbior.2014.04.004]
Martelli, Am; Lonetti, A; Buontempo, F; Ricci, F; Tazzari, Pl; Evangelisti, C; Bressanin, D; Cappellini, A; Orsini, E; Chiarini, F
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1288407
Citazioni
  • ???jsp.display-item.citation.pmc??? 13
  • Scopus 36
  • ???jsp.display-item.citation.isi??? ND
social impact