Molecular Pathways TLX1-Induced T-cell Acute Lymphoblastic Leukemia
نویسندگان
چکیده
The TLX1 transcription factor oncogene is frequently activated by chromosomal translocations in T-cell acute lymphoblastic leukemia (T-ALL) and defines a distinct molecular group of tumors characterized by differentiation arrest at the early cortical stage of thymocyte differentiation and excellent response to therapy. Recent developments from the analysis of genomic data on TLX1-specific transcriptional targets and analysis of the molecular mechanisms of TLX1 transformation in humanand mouse-induced leukemias have shown novel insight into the activity of this transcription factor oncogene. Aberrant expression of TLX1 in T-cell progenitors disrupts normal T-cell development and triggers the development of aneuploidy during T-cell transformation. Importantly, the disruption of the mitotic checkpoint in TLX1-induced tumors may be linked not only to the acquisition of secondary genetic alterations in T-ALL but also to increased sensitivity of these tumors to chemotherapy with drugs targeting the formation of the mitotic spindle. Clin Cancer Res; 17(20); 6381–6. 2011 AACR.
منابع مشابه
Transient Responses to NOTCH and TLX1/HOX11 Inhibition in T-Cell Acute Lymphoblastic Leukemia/Lymphoma
To improve the treatment strategies of T-cell acute lymphoblastic leukemia/lymphoma (T-ALL), further efforts are needed to identify therapeutic targets. Dysregulated expression of HOX-type transcription factors occurs in 30-40% of cases of T-ALL. TLX1/HOX11 is the prototypical HOX-type transcription factor. TLX1 may be an attractive therapeutic target because mice that are deficient in TLX1 are...
متن کاملTLX1-induced T-cell acute lymphoblastic leukemia.
The TLX1 transcription factor oncogene is frequently activated by chromosomal translocations in T-cell acute lymphoblastic leukemia (T-ALL) and defines a distinct molecular group of tumors characterized by differentiation arrest at the early cortical stage of thymocyte differentiation and excellent response to therapy. Recent developments from the analysis of genomic data on TLX1-specific trans...
متن کاملPrognostic and oncogenic relevance of TLX1/HOX11 expression level in T-ALLs.
TLX1 is a homeodomain transcription factor generally associated with a favorable outcome in T-cell acute lymphoblastic leukemia (T-ALL). However, the molecular mechanisms of TLX1 deregulation remain unclear and various transcript levels in the absence of 10q24 abnormalities have been reported. A reproducible and accurate delineation of TLX1(+) T-ALL will be necessary for proper therapeutic stra...
متن کاملProlonged Vincristine Toxicity Induced by Concurrent Posaconazole in a Child with T-cell Acute Lymphoblastic Leukemia
متن کامل
Proteasome Inhibition by Carfilzomib Induced Apotosis and Autophagy in a T-cell Acute Lymphoblastic Leukemia Cell Line
T-cell acute lymphoblastic leukemia is an aggressive hematologic malignancy which is usuallyassociated with unfavorable prognosis particularly in patients with refractory/relapsed disease.Therefore, development of novel therapeutic strategies is highly required for improving theoutcome of these patients. Although there are several studies evaluating the efficacy of proteasome<...
متن کامل