Molecular features of leukemia cutis in acute myeloid leukemia

Summary: Leukemia cutis (LC) represents cutaneous infiltration by neoplastic leukemic cells, serving as an important extramedullary manifestation of systemic leukemia. Previous studies have found associations between LC in patients with acute myeloid leukemia (AML) and decreased overall and leukemia-specific survival¹. However, the pathogenesis and molecular features of LC remain poorly understood. A retrospective matched-cohort study was performed including 47 AML patients with LC diagnosed from November 2006 to December 2021 propensity-matched to 141 AML patients without LC, finding that the most frequent molecular alterations in LC were NPM1 mutations (38%, p < 0.001), followed by aberrancies in composite FLT3 (28%, p < 0.05), chromosome 8 (23%, p < 0.05), and NRAS/KRAS (21%, p < 0.01). Two of the LC patients had molecular studies performed on skin biopsy samples, both of which carried NPM1 (frameshifts in W288) and KRAS mutations. A literature review revealed studies demonstrating correlation of NPM1 mutations with cutaneous AML including a report of NPM1 mutations in the C-terminus (such as frameshifts in W288) found in 70% skin samples². LC emergence can precede bone marrow involvement suggesting its utility as a biomarker. These molecular insights provide potential therapeutic targets and prognostic indicators that may enhance clinical management of this condition. ¹Wang CX et al. Association of Leukemia Cutis With Survival in Acute Myeloid Leukemia. <i>JAMA Dermatol.</i> 2019;155(7):826–32. ²Sadigh S et al. Cutaneous Manifestations of Myeloid Neoplasms Exhibit Broad and Divergent Morphologic and Immunophenotypic Features but Share Ancestral Clonal Mutations With Bone Marrow. <i>Mod. Pathol.</i> 2024;37(1):100352. Jonathan J. Park¹, Grant Z. Zhao¹, Samantha M. Guhan¹, Christopher S. Yang¹, Cuong Nguyen¹ 1. Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States. Clinical Research: Epidemiology and Observational Research