TY  - JOUR
A1  - Bartram, Isabelle
A1  - Gökbuget, Nicola
A1  - Schlee, Cornelia
A1  - Heesch, Sandra
A1  - Fransecky, Lars
A1  - Schwartz, Stefan
A1  - Stuhlmann, Reingard
A1  - Schäfer-Eckhart, Kerstin
A1  - Starck, Michael
A1  - Reichle, Albrecht
A1  - Hoelzer, Dieter
A1  - Baldus, Claudia
A1  - Neumann, Martin
T1  - Low expression of T-cell transcription factor BCL11b predicts inferior survival in adult standard risk T-cell acute lymphoblastic leukemia patients
T2  - Journal of hematology & oncology
N2  - Background: Risk stratification, detection of minimal residual disease (MRD), and implementation of novel therapeutic agents have improved outcome in acute lymphoblastic leukemia (ALL), but survival of adult patients with T-cell acute lymphoblastic leukemia (T-ALL) remains unsatisfactory. Thus, novel molecular insights and therapeutic approaches are urgently needed.
Methods: We studied the impact of B-cell CLL/lymphoma 11b (BCL11b), a key regulator in normal T-cell development, in T-ALL patients enrolled into the German Multicenter Acute Lymphoblastic Leukemia Study Group trials (GMALL; n = 169). The mutational status (exon 4) of BCL11b was analyzed by Sanger sequencing and mRNA expression levels were determined by quantitative real-time PCR. In addition gene expression profiles generated on the Human Genome U133 Plus 2.0 Array (affymetrix) were used to investigate BCL11b low and high expressing T-ALL patients.
Results: We demonstrate that BCL11b is aberrantly expressed in T-ALL and gene expression profiles reveal an association of low BCL11b expression with up-regulation of immature markers. T-ALL patients characterized by low BCL11b expression exhibit an adverse prognosis [5-year overall survival (OS): low 35% (n = 40) vs. high 53% (n = 129), P = 0.02]. Within the standard risk group of thymic T-ALL (n = 102), low BCL11b expression identified patients with an unexpected poor outcome compared to those with high expression (5-year OS: 20%, n = 18 versus 62%, n = 84, P < 0.01). In addition, sequencing of exon 4 revealed a high mutation rate (14%) of BCL11b.
Conclusions: In summary, our data of a large adult T-ALL patient cohort show that low BCL11b expression was associated with poor prognosis; particularly in the standard risk group of thymic T-ALL. These findings can be utilized for improved risk prediction in a significant proportion of adult T-ALL patients, which carry a high risk of standard therapy failure despite a favorable immunophenotype.
KW  - Adult T-cell acute lymphoblastic leukemia
KW  - BCL11b
KW  - Outcome
KW  - Standard risk
KW  - Expression
KW  - Mutation
Y1  - 2014
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/34716
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-347168
SN  - 1756-8722
VL  - 7
IS  - 51
SP  - 1
EP  - 10
PB  - BioMed Central
CY  - London
ER  -