ETV6-RUNX1 Rearrangement in Tunisian Pediatric B-Lineage Acute Lymphoblastic Leukemia

Area of Science:

• Pediatric Oncology
• Molecular Genetics
• Hematology

Background:

• B-lineage acute lymphoblastic leukemia (B-ALL) is the most common childhood cancer.
• The t(12;21) translocation, resulting in the ETV6-RUNX1 fusion gene, is a frequent genetic abnormality in B-ALL.
• Understanding genetic alterations is crucial for prognosis and treatment strategies in pediatric B-ALL.

Purpose of the Study:

• To determine the incidence of the t(12;21) translocation and ETV6-RUNX1 fusion gene in Tunisian children with B-ALL.
• To investigate additional genetic abnormalities, such as RUNX1 gene copy number variations, in pediatric B-ALL patients.
• To explore the role of secondary genetic changes in the context of ETV6-RUNX1 fusion in disease progression.

Main Methods:

• Fluorescence in situ hybridization (FISH) was employed to detect the t(12;21) translocation.
• Analysis included evaluation for ETV6-RUNX1 rearrangement, loss of ETV6 alleles, and extra copies of the RUNX1 gene.
• The study focused on Tunisian pediatric patients diagnosed with B-ALL lacking detectable recurrent abnormalities.

Main Results:

• The ETV6-RUNX1 rearrangement was identified in 16 out of 57 (28%) Tunisian children with B-ALL.
• Two patients exhibited loss of a normal ETV6 allele, and three showed an extra RUNX1 gene signal.
• Seven patients without ETV6-RUNX1 rearrangement had extra RUNX1 gene signals, with one also having a t(3;12) translocation.

Conclusions:

• This is the first Tunisian study reporting the incidence of t(12;21) in childhood B-ALL and identifying multiple RUNX1 gene copies.
• The findings highlight the common occurrence of additional or secondary genetic changes in pediatric B-lineage ALL with ETV6-RUNX1 fusion.
• These genetic alterations are suggested to play a significant role in the progression of pediatric B-ALL.