Expression of HOX11 in childhood T-lineage acute lymphoblastic leukaemia can occur in the absence of cytogenetic aberration at 10q24: a study from the Children's Cancer Group (CCG).
Clonal genetic aberrations in tumour cells provide critical information for the development of new diagnostic and therapeutic strategies for patients. In paediatric T-cell acute lymphoblastic leukaemia (T-ALL) chromosomal translocations are present in 30-35% of cases. HOX11 and the closely related HOX11L2 genes play a key role in T-ALL. HOX11 is aberrantly activated by either of the two chromosomal translocations, t(7;10) and t(10;14). In this study, HOX11 expression levels were measured by real-time quantitative reverse-transcriptase polymerase chain reaction. We show that leukaemic blasts from 15/76 (19.7%) paediatric T-ALL patients expressed the HOX11 gene at high level and 22/76 (28.9%) at low level, yet the reported frequency for chromosomal rearrangement of 10q24 is 4-7%. Direct cytogenetic analysis revealed that only 2/16 specimens that showed HOX11 expression exhibited abnor-malities at 10q24. These results confirm and extend our previously published findings, and implicate mechanisms other than gross chromosomal translocations for the deregulation of HOX11. Analysis of clinical outcome for the whole study group showed a trend for better outcome for patients with leukaemic blasts expressing HOX11 at high level. A statistically significant difference in clinical outcome was found in a subgroup of 20 patients treated for high-risk disease on CCG-1901 from the Children's Cancer Group, where HOX11 expression in leukaemic blasts conferred a prognostic advantage (P=0.01).
Division of Children's Leukaemia and Cancer Research, Telethon Institute for Child Health Research and Centre for Child Health Research, The University of Western Australia, Perth, Australia.
U R
UR
Kees
N A
NA
Heerema
R
R
Kumar
P M
PM
Watt
D L
DL
Baker
M K
MK
La
F M
FM
Uckun
H N
HN
Sather
D001853:Bone Marrow; D019070:Cell Lineage; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D020732:Cytogenetic Analysis; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007223:Infant; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics*; D008297:Male; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D011003:Ploidies; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000235:genetics; D015996:Survival Rate; D014178:Translocation, Genetic / Q000235:genetics*; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D018398:Homeodomain Proteins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C071250:TLX1 protein, human