Acute Myeloid Leukemia with Myelodysplasia-Related Changes (AML-MRC) with SH2B3, IDH2, CEBPA, RUNX1, and PRPF8 Mutations: A Case Report

Acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) is a diverse and intricate myeloid malignancy characterized by dysplasia in multiple blood cell types, cytogenetic abnormalities, and poor clinical outcomes. Genetic aberrations are fundamental to its development, with common mutations including SRSF2, SF3B1, ZRSF2, and U2AF1, which disrupt RNA splicing and impair hematopoiesis. This report details a rare case of AML-MRC in a 29-year-old female, initially presenting with 33.6% myeloblasts and 18.4% monoblasts in the bone marrow, later showing features of myelodysplasia, and ultimately relapsing with 94.3% myeloblasts. Comprehensive next-generation sequencing identified SH2B3, IDH2, CEBPA, RUNX1, and PRPF8 mutations, a profile more typical of de novo AML. These mutations disrupt key cellular processes such as cytokine signaling, epigenetic regulation, transcriptional control, and RNA splicing, contributing to genomic instability and disease progression. This case highlights significant laboratory findings, including initial high blast counts and the specific mutational landscape, underscoring the genetic heterogeneity of AML-MRC and emphasizing the necessity for thorough molecular profiling and targeted therapies to improve patient outcomes.