Interphase-FISH screening for eight common rearrangements in pediatric B-cell precursor acute lymphoblastic leukemia

This is the first pilot study to screen multiple common genetic aberrations in B-cell precursor acute lymphoblastic leukemia (BCP-ALL).

Thirty-two children with BCP-ALL were investigated for chromosomal rearrangements using interphase fluorescence in situ hybridization (FISH). Eight common translocations and rearrangements, including ETV6-RUNX1, TCF3-PBX1, BCR-ABL1, ETV6, TCF3, MLL, IGH@, and PAX5, were tested for using dual-color DNA probes.

ETV6-RUNX1 was the most frequent translocation detected in 11 children (34.4%). Two patients with BCR-ABL1 (6.3%) and one with TCF3-PBX1 (3.1%) translocations were also observed. Using break-apart probes, 11 children (34.4%) had a positive FISH result for ETV6, two patients for IGH@ (6.3%), one patient for MLL (3.1%), and one patient for PAX5 rearrangements (3.1%). All patients with the ETV6-RUNX1 fusion were also identified by split signals for ETV6. Other abnormalities, including extra copies and deletion of genes, were observed within the range of 3.1-34.4%. Cytogenetics analysis showed a single case each of BCR-ABL1 fusion, MLL, and IGH@ rearrangements (3.1% each). ETV6-RUNX1 fusion and ETV6 split-apart rearrangements were not visible by cytogenetics. Likewise, one each of cases with TCF3-PBX1 fusion and with PAX5 split signal seen by FISH was not visible by cytogenetics.

By using 8 FISH probes in conjunction cytogenetics for the detection of common aberrations, interphase FISH enhanced the detection of chromosomal rearrangements in children with BCP-ALL.