Identification of a Novel RUNX1::STX2 Fusion in Mixed-Phenotype Acute Leukemia (MPAL) With BCR::ABL1.

Abstract

Mixed phenotype acute leukemia (MPAL) is a rare type of acute leukemia (AL), MPAL with BCR::ABL1 fusion is the main subtype of MPAL, mainly affecting adult males. It is an acute leukemia with unique clinical and biological characteristics that involve both the myeloid and lymphatic systems. Gene fusion plays a crucial role in the pathogenesis, diagnosis, prognosis assessment, and treatment of leukemia. We present the first discovery of a novel fusion of RUNX1::STX2 in this subtype, which is co-expressed with BCR::ABL1 fusion. RUNX1 is a crucial transcription factor for hematopoietic differentiation, frequently found to be abnormal in AML, while STX2 may play a role in cancer progression. The RUNX1::STX2 fusion protein may act as the primary negative regulator of wild-type RUNX1, influencing normal cell differentiation and proliferation, consequently elevating the risk of leukemia. The gene fusion status of this patient is unique and complex, requiring further exploration to understand its functional significance in leukemia progression and treatment response.