Aberrant signaling in T-cell acute lymphoblastic leukemia: biological and therapeutic implications.
T-cell acute lymphoblastic leukemia (T-ALL) is a biologically heterogeneous disease with respect to phenotype, gene expression profile and activation of particular intracellular signaling pathways. Despite very significant improvements, current therapeutic regimens still fail to cure a portion of the patients and frequently implicate the use of aggressive protocols with long-term side effects. In this review, we focused on how deregulation of critical signaling pathways, in particular Notch, PI3K/Akt, MAPK, Jak/STAT and TGF-beta, may contribute to T-ALL. Identifying the alterations that affect intracellular pathways that regulate cell cycle and apoptosis is essential to understanding the biology of this malignancy, to define more effective markers for the correct stratification of patients into appropriate therapeutic regimens and to identify novel targets for the development of specific, less detrimental therapies for T-ALL.
Cardoso
B A
BA
Unidade de Biologia do Cancro, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
Gírio
A
A
Henriques
C
C
Martins
L R
LR
Santos
C
C
Silva
A
A
Barata
J T
JT
D002454:Cell Differentiation; D006801:Humans; D053612:Janus Kinases / Q000502:physiology; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000209:etiology / Q000503:physiopathology / Q000628:therapy; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010766:Phosphorylation; D010770:Phosphotransferases / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D051880:Receptors, Notch / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology*; D016212:Transforming Growth Factor beta / Q000502:physiology
D051880:Receptors, Notch; D016212:Transforming Growth Factor beta; D010770:Phosphotransferases; D019869:Phosphatidylinositol 3-Kinases; D053612:Janus Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases