Abstract

ABSTRACT 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.