P087 | From Xenograft to Patient: the Impact of Surface Markers on Acute Myeloid Leukemia Extramedullary Invasion
Year: 2025
Type: article
Abstract: Acute myeloid leukemia (AML) is a heterogeneous malignancy of hematopoietic progenitors and the most common acute leukemia in adults. Adhesion molecules involved in leukocyte trafficking are thought to contribute to extramedullary AML (EM-AML), a manifestation associated with aggressive phenotype, poor prognosis, and low remission rates. Despite its clinical impact, the molecular mechanisms driving EM localization remain largely undefined. AML blast cells from 7 patients were engrafted into NOD SCID/IL2Rγ-null mice to generate patient-derived xenograft (PDX) models. Surface markers involved in leukocyte trafficking (CD56, CXCR4, CCR7) and EM-AML (CD117) were analyzed by flow cytometry and immunohistochemistry. Paired samples from bone marrow (BM)/peripheral blood and EM sites were compared. EM infiltration was reproduced across multiple organs—including spleen, liver, meninges, and lungs—with each PDX showing a distinct pattern, suggesting blast-intrinsic organ tropism. Blasts from different tissues of the same mouse displayed distinct surface marker profiles, stable across passages. For example, in PDX#1, CXCR4+/CCR7- blasts predominated in bone marrow and spleen, while double-negative cells localized in the lung (Fig. 1a). These profiles were validated in human samples: in one case of leukemic meningitis, meningeal blasts expressed bright CCR7, contrasting with low CCR7 in circulating blasts (Fig. 1b). Similar differences were seen in leukemia cutis vs. BM pairs (Fig 1c). Bioinformatic analysis confirmed CD117, CD56, CXCR4, and CCR7 expression across all ICC 2022 AML categories, with CD56 enriched in t(8;21) AML, a subtype often linked to EM involvement. Our translational study shows, from xenograft to patient, that EM-AML is driven by phenotypically distinct leukemic subpopulations with organ-specific marker patterns. These findings support future therapeutic strategies targeting EM tropism in AML.
Authors: M. Caridi*, S. Cipriani*, F. Milano, K. E. Jardini, R. Ranieri, S. Boroumand Noughabi, B. Bigerna, A. Tabarrini, C. Caterino, G. Cimino, V. Cardinali, L. Ruggeri^, M.P. Martelli^
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7093123065
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