Genomic and Clinicopathological Characterization of CRLF2-Rearranged Mixed Phenotype Acute Leukemia

Rearrangements of cytokine receptor-like factor 2 gene (CRLF2) are present in ∼50% of B-lymphoblastic leukemia/lymphoma (B-ALL) with BCR::ABL1-like features. Herein, we report three patients with CRLF2-rearranged mixed phenotype acute leukemia (MPAL). All three cases were B/myeloid MPAL in young patients harboring P2RY8::CRLF2 or IGH::CRLF2 with additional genomic alterations in signaling (JAK and RAS) and cell cycle (CDKN2A/B) pathways, a genomic profile similar to that in BCR::ABL1-like B-ALL. Our study is the first case series to demonstrate clinicopathological and genomic features of this underrecognized entity. We recommend upfront genetic/molecular testing to timely diagnose and further characterize MPAL with BCR::ABL1-like features.