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Molecular Cancer
Published in: Molecular Cancer 1/2018

Open Access 01-12-2018 | Review

Non ABL-directed inhibitors as alternative treatment strategies for chronic myeloid leukemia

Authors: Michele Massimino, Stefania Stella, Elena Tirrò, Chiara Romano, Maria Stella Pennisi, Adriana Puma, Livia Manzella, Antonino Zanghì, Fabio Stagno, Francesco Di Raimondo, Paolo Vigneri

Published in: Molecular Cancer | Issue 1/2018

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Abstract

The introduction of ABL Tyrosine Kinase Inhibitors (TKIs) has significantly improved the outcome of Chronic Myeloid Leukemia (CML) patients that, in large part, achieve satisfactory hematological, cytogenetic and molecular remissions. However, approximately 15–20% fail to obtain optimal responses according to the current European Leukemia Network recommendation because of drug intolerance or resistance.
Moreover, a plethora of evidence suggests that Leukemic Stem Cells (LSCs) show BCR-ABL1-independent survival. Hence, they are unresponsive to TKIs, leading to disease relapse if pharmacological treatment is discontinued.
All together, these biological events generate a subpopulation of CML patients in need of alternative therapeutic strategies to overcome TKI resistance or to eradicate LSCs in order to allow cure of the disease.
In this review we update the role of “non ABL-directed inhibitors” targeting signaling pathways downstream of the BCR-ABL1 oncoprotein and describe immunological approaches activating specific T cell responses against CML cells.
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Metadata
Title
Non ABL-directed inhibitors as alternative treatment strategies for chronic myeloid leukemia
Authors
Michele Massimino
Stefania Stella
Elena Tirrò
Chiara Romano
Maria Stella Pennisi
Adriana Puma
Livia Manzella
Antonino Zanghì
Fabio Stagno
Francesco Di Raimondo
Paolo Vigneri
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2018
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-018-0805-1

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