Supplementary Material for: A New t(8;9) Translocation Involving the JAK2 Gene in Acute Myeloid Leukemia: a Case Report

Abstract Introduction: Acute myeloid leukemia (AML) is a molecularly and clinically heterogeneous disease. Nearly 50% of patients exhibit a normal karyotype, although genomic aberrations are recurrent. Translocations involving JAK2 have increasingly been identified in patients with JAK2V617F-negative myeloproliferative neoplasms (MPNs), as well as in various other hematologic diseases. Here, we present a unique case of a de novo AML patient with a t(8;9)(p22;p24) translocation, resulting in HMBOX1::JAK2 fusion. Case presentation: The patient exhibited anemia, leukocytosis, and thrombocytopenia, with bone marrow analysis revealing a significant population of CD34+CD33+ myeloid blasts. The conventional cytogenetic analysis initially showed a normal karyotype, later identifying the t(8;9) translocation after relapse. Molecular characterization of the translocation allowed us to delineate the breakpoints regions, which map to exon 5 of the HMBOX1 gene and exon 19 of the JAK2 gene. The resulting transcript was an in-frame fusion. The patient was diagnosed with acute monocytic leukemia. Induction chemotherapy (cytarabine and idarubicin) initially achieved remission, but subsequent relapses led to the use of venetoclax and 5-azacytidine, which again resulted in remission. Unfortunately, disease progression followed, and the patient ultimately succumbed to AML. Conclusion: This is the first report that molecularly characterize the HMBOX1::JAK2 fusion in a de novo AML patient. The identification of this novel alteration adds to the growing and heterogeneous molecular landscape of AML and suggests a potential new avenue for targeted therapy.