Multimodal assessment of chronic myelomonocytic leukemia with extramedullary involvement reveals RAS pathway activation, adverse outcomes and epithelial-mesenchymal transition

作者：Sanam Loghavi, Chenxuan Zang, Ziyi Li, Danielle Hammond, Kelly S. Chien, Álex Bataller, Alexandre Bazinet, Koji Sasaki, Elias Jabbour, Courtney D. DiNardo, Nicholas J. Short, Ghayas C. Issa, Naveen Pemmaraju, Tapan M. Kadia, Farhad Ravandi, Naval Daver, Gautam Borthakur, Rashmi Kanagal‐Shamanna, Peng Wei, Sa Wang, Wei Wang, Hong Fang, Guilin Tang, Sherry Pierce, Carlos E. Bueso‐Ramos, L. Jeffrey Medeiros, Hagop M. Kantarjian, Guillermo Garcia-Manero, Guillermo Montalban‐Bravo · 发表于：Blood · 年份：2025 · DOI：10.1182/blood-2025-3848 · 被引用次数：2 · 研究领域：Acute Myeloid Leukemia Research、Chronic Lymphocytic Leukemia Research、Myeloproliferative Neoplasms: Diagnosis and Treatment

Abstract Background: Extramedullary disease (EMD) in chronic myelomonocytic leukemia (CMML) patients (pts) remains poorly characterized with limited data on its genetic, phenotypic, and biological characteristics, and its clinical implications. Further understanding of EMD in CMML could inform therapeutic strategies aimed at preventing or treating EMD in CMML. Methods We evaluated 574 pts with CMML and further selected pts with biopsy-proven EMD. Clinically detected hepatosplenomegaly or biopsy-proven splenic EMD were not included. Histopathologic review was performed independently by two hematopathologists. Immunohistochemistry and/or flow cytometry (FC) were used to determine the immunophenotype of EMD. CD56 expression in bone marrow (BM) monocyte and blast populations was evaluated by FC. Next generation sequencing (NGS) was performed on BM specimens (n=452) at time of diagnosis and on EMD sites (n=5). Variant allele frequency (VAF) estimates were used to evaluate clonal relationships. Spatial transcriptomics (Visium HD) was applied to EMD tissue sites in two representative cases. Results Among 63 patients with EMD-CMML, 36 (57%) had myeloproliferative (MP) CMML, and 11 (18%) had CMML-2. EMD-CMML pts had similar baseline characteristics compared to those without EMD (n=511) except for male predominance (79% vs 69%, p=0.003). Renal failure at time of EMD diagnosis was observed in 18/52 (35%) evaluable pts. No significant differences in CD56+ monocyte or CD56+/CD34+ blast fr...