SFPQ-ABL1-positive B-cell precursor acute lymphoblastic leukemias

Area of Science:

• Hematology
• Oncology
• Molecular Biology

Background:

• A subset of B-cell precursor acute lymphoblastic leukemia (BCP ALL), termed "B-other", lacks defined genetic abnormalities.
• ABL-class gene rearrangements (ABL1, ABL2, CSF1R, PDGFRB) characterize some BCP ALL cases.
• Identifying specific genetic drivers is crucial for targeted therapy in BCP ALL.

Purpose of the Study:

• To investigate the prevalence of ABL-class gene aberrations in adult and pediatric B-other BCP ALL.
• To characterize a rare SFPQ-ABL1 fusion identified in an adult BCP ALL case.
• To review existing literature on SFPQ-ABL1 fusions to inform treatment strategies.

Main Methods:

• Fluorescence in situ hybridization (FISH) was used to screen 105 B-other BCP ALL cases (55 pediatric, 50 adult) for ABL-class gene rearrangements.
• Reverse transcription polymerase chain reaction (RT-PCR) and sequencing were employed to confirm gene fusions.
• A literature review was conducted on previously reported SFPQ-ABL1 positive cases.

Main Results:

• ABL-class aberrations were detected in 6% of adult B-other BCP ALL cases, but none in pediatric cases.
• A novel SFPQ-ABL1 fusion was identified in one adult BCP ALL case with a t(1;9)(p34;q34) translocation.
• Review of six previously reported SFPQ-ABL1 positive cases revealed a common SFPQ exon 9 to ABL1 exon 4 fusion, typically in adolescents/young adults without hyperleukocytosis, and recurrent IKZF1 deletions.

Conclusions:

• ABL-class gene aberrations, particularly SFPQ-ABL1 fusions, represent a distinct subgroup of BCP ALL in adults.
• The recurrent nature of the SFPQ-ABL1 fusion and associated IKZF1 deletions suggests a specific molecular pathogenesis.
• Relapse in patients not receiving tyrosine kinase inhibitors (TKIs) and/or allogeneic stem cell transplantation underscores the importance of TKI therapy for SFPQ-ABL1 positive BCP ALL.