446 Shared NRAS Mutation in Concurrent inv(16) Acute Myeloid Leukemia(AML) and Chronic Lymphocytic Leukemia(CLL): Possible Overlapping Clonal Architecture

Introduction/Objective AML in CLL patients is rare, often therapy-related, and linked to poor outcomes. Incidence is under 1% but rises after fludarabine, cyclophosphamide, and rituximab (FCR), linked to secondary AML or MDS. NRAS codon 61 mutations (Q61K) occur in 10–30% of AML cases but are infrequent (∼2.4%) in CLL. Their presence in both indicates clonal evolution, necessitating further investigation. Methods/Case Report A 65-year-old woman diagnosed with CLL six months earlier presented with rising leukocytosis and splenomegaly. Work-up included bone marrow biopsy, flow cytometry, cytogenetics, FISH, FLT3 ITD, and a 58-gene myeloid panel NGS. The biopsy revealed AML with 40–55% blasts. Flow cytometry indicated 16% CD34+ blasts with a CD33 and monocytic component, consistent with AML, alongside a kappa-restricted CD5+ B-cell population indicating concurrent CLL. Cytogenetics and FISH confirmed core-binding factor AML with inv(16) [CBFβ]. FLT3-ITD was negative. NGS identified an NRAS Q61K mutation (variant allele frequency 30%) in the original bone marrow biopsy. The NRAS Q61K variant was later detected in CLL and blast populations via microdissected paraffin-embedded slides. Results NA Conclusion This case suggests a clonal link between CLL and AML through an NRAS mutation identified in microdissected blasts and lymphoma cells. Venetoclax-rituximab shows promise; however, further studies are needed to clarify molecular drivers and guide targeted therapies in dual hematologic malignancies.