Expression pattern of homeodomain genes does not define the known subgroups of childhood acute lymphoblastic leukemias
Abstract
Objective: The main immunophenotype and genotype subgroups of the childhood acute lymphoblastic leukemias (ALL) have characteristic RNA expression profile. The homeodomain genes (HOX) play an important role in normal hemopoiesis and their role is presumed in pathogenesis of acute leukemias as well.
The authors investigated, whether the expression profile of 21 HOX genes of the HOXA, HOXB and CDX group defines selected immunophenotype and genotype groups of children ALL. In comparison with the HOX gene expression in physiological precursors of lymphoid cells we followed whether the expression in malignant cells reflects their relative maturity.
Methods: HOX gene expression was analyzed by using quantitative RT-PCR in the group of children ALL and normal precursors of lymphoid cells. Analysis of the data was made by the hierarchical clustering analysis.
Results: In spite of the fact that expression of individual HOX genes differed significantly among individual groups of the children ALL (T-ALL, B precursor ALL with fusion genes TEL/AMLI, BCR/ABL, MLL/AF4 and hyperdiploid one), the total expression profile failed to define the individual subgroups reliably. The comparison of expression of individual HOX genes in the developmental stages of physiological lymphoid cells made it clear that their malignant counterparts express the HOX genes independently of their relative maturity.
Conclusions: Leukemia cells express aberrantly selected HOX genes. However, the determination of expression profile of HOX genes is not a suitable remedy for classification of childhood leukemia.
Highly expressed HOX genes in individual subgroups can potentially serve as targets of biological therapy.