Based on these findings, we identify a synergistic role between TLX1/HOX11 overexpression and Ubr1 inactivation in promoting chromosome missegregation, permitting the accrual of additional chromosome losses and cytogenic abnormalities en route to malignancy.
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).
Evaluation of the expression of three T-cell malignancy associated genes showed that Rhombotin-2 (RBTN-2 also known as Lmo-2), TAL-1 (also known as SCL), and HOX-11 were expressed in 100%, 40%, and 0% of the murine tumors, respectively.
In order to assess whether HOX11 expression is present in other pediatric malignancies we examined a panel of 20 tumor cell lines established from solid tumors and leukemias, but none of them showed expression of HOX11.
The results support the hypothesis that the transforming capacity of HOX11 derives from its ability to alter the expression of genes regulating hematopoietic differentiation and that secondary mutations promoting cell survival or stimulating proliferation are required for progression to malignancy.
Since, in addition to our cases, involvement of the 9q34 breakpoint, together with 2q33, 14q11, or 7q34, has been reported in the literature in four lymphoblastic lymphoma patients, a gene located in 9q34 and referred to as tcl-3 may participate in the genesis of the T cell malignancies carrying these translocations.