Philadelphia chromosome-like acute lymphoblastic leukemia with concomitant rearrangements of CRLF2 and ABL1: a pediatric case report

Background BCR::ABL1-like or Philadelphia chromosome-like (Ph-like) acute lymphoblastic leukemia (ALL) was first reported in 2009. Ph-like ALL is characterized by gene signature similar to Philadelphia chromosome ALL, but without BCR::ABL1 fusions. Molecularly, Ph-like ALL is divided into seven categories, with CRLF2 and ABL-class rearrangements being the two most common subtypes, exhibiting alterations in distinct downstream signaling cascades. Case presentation We report a rare case of pediatric Ph-like ALL with concomitant CRLF2 and ABL1 rearrangements. CRLF2 was fused with P2RY8, its most common fusion partner, whereas ABL1 was fused with MYO18B, a novel fusion partner that has not been previously reported. The 4-year-old female patient was treated using the national multicenter CCCG-ALL-2020 protocol with the addition of dasatinib at the end of induction when ABL1 rearrangement was confirmed by RNA-seq. Morphologically and molecularly, the patient remained in continuous remission until the last follow-up. To the best of our knowledge, this is the first case of Ph-like ALL harboring two distinct rearrangement categories. Conclusions Our results identified that ABL1 rearrangement and CRLF2 rearrangement can coexist. The application of FISH, whole transcription sequencing, PCR can help us to have a more comprehensive understanding of ALL cytogenetics and molecular biology. Further studies are needed to explore the role of targeted therapies in such rare clinical scenarios.