Acute lymphoblastic leukemia (ALL) is the most common childhood cancer type. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive and quickly progressing type of ALL affecting T-lymphocytes. Genomic data suggests that more than 10 functional aberrations are contributing to the development of this disease. T-ALL cases can be grouped by distinct genetic profiles and the aberrant expression of a characteristic transcription factor. Major subgroups are characterized by ectopic expression of TAL1, TLX1, TLX3, HOXA9/10, LMO2 or NKX2-1 and others as a result of chromosomal rearrangements or mutations. About 20% of childhood T-ALL cases are characterized by aberrant expression of TLX3 as a result of t(5;14)(q35;q32). This cryptic translocation juxtaposes TLX3, normally not expressed in T-cells, with the BCL11B gene, which is active in T-cells, resulting in ectopic expression of TLX3.
Fluorescence in situ hybridization is a valuable method for the detection of t(5;14)(q35;q32) since cryptic translocations may escape during classical cytogenetic analysis. Furthermore, the broad range of breakpoints in the chromosomal region 14q32 makes the development of efficient PCR-based methods difficult.
Clinical Applications
- Acute Lymphoblastic Leukemia (ALL)