The dual role of HLXB9 in leukemia.
BACKGROUND
The HLXB9 gene encodes a homeodomain containing transcription factor which has been implicated in the development of both solid and hematological malignancies. In leukemia it is one of the two fused genes, along with ETV6, in a recurrent translocation frequently observed in infant AML.


METHODS
Here we investigate the role of epigenetic inactivation of the HLXB9 gene in leukemia. Quantitative DNA methylation analysis was performed using the COBRA assay, and qRT-PCR was used to assess the effects of methylation on expression in hematological cell lines and primary ALL samples.


RESULTS
Hypermethylation of the HLXB9 gene was found to be a frequent event in childhood ALL, occurring in 33% of cases. However, it was rarely or never observed in other types of leukemia, including AML, CML, and CLL, with the exception of adult ALL, in which 39% of cases were hypermethylated. Furthermore, hypermethylation of HLXB9 results in loss of expression in hematological cell lines and primary ALL samples.


CONCLUSIONS
These results suggest that HLXB9 may have a dual role in childhood leukemia, as an oncogene in infant AML but as a tumor suppressor in childhood ALL.
Crucible Laboratory, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK.
Stuart
S
Ferguson
Hannah E
HE
Gautrey
Gordon
G
Strathdee
D000328:Adult; D002648:Child; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D018398:Homeodomain Proteins; C490003:MNX1 protein, human; D014157:Transcription Factors