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. 2025 Aug 1;110(8):1870-1874.
doi: 10.3324/haematol.2024.287096. Epub 2025 Mar 6.

Hepatocyte senescence and persistent liver injury in Fanconi anemia

Jane Koo  1 , Alana J Snyder  2 , Kathleen Campbell  3 , Erica Miller  2 , Allison O'Conner  2 , Markus Grompe  4 , Parinda A Mehta  2 , Kasiani C Myers  2 , Stella M Davies  2
Affiliations

Hepatocyte senescence and persistent liver injury in Fanconi anemia

Jane Koo et al. Haematologica. .
No abstract available

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Figures

Figure 1.
Figure 1.
Clinical time courses of patients in the liver biopsy cohort with persistent liver injury, demonstrating progressive liver disease. (A-C) A visual panel of the clinical course of each patient is depicted, including the progression of liver enzyme testing, the evolution of clinical symptoms, liver imaging findings, and treatments administered. The table summarizes the clinical characteristics of each patient. HSCT: hematopoietic stem cell transplant; ALT: alanine aminotransferase; AST: aspartate aminotransferase; PLI: persistent liver injury; MUD: matched unrelated donor; MMF: mycophenolate mofetil; MMUD: mismatched unrelated donor; GVHD: graft-versus-hostdisease; Cy: cyclophosphamide; Flu: fludarabine; Bu: busulfan; CSA: cyclosporine; Pred: prednisone; CT: computed tomography; US: ultrasound.
Figure 2.
Figure 2.
Immunohistochemistry staining of liver biopsies for multiple markers with a proposed role in the pathogenesis of persistent liver injury from three separate patients with Fanconi anemia display important differences in the patients with liver injury and are negative in a matched Fanconi anemia control without transaminitis. (A-F) Immunohistochemistry (IHC) for proliferating cell nuclear antigen (PCNA) demonstrates widespread moderate to strong positivity while it is negative in the Fanconi anemia (FA) control. Increased positivity is observed in subsequent samples for patients 1 and 2. (G-L) IHC staining of Kupffer cells marked by CD68 shows diffusely scattered positive cells in FA cases while negative in the FA control. (M-R) Staining for cyclin-dependent kinase inhibitor 1 (p21), a marker of cellular senescence, demonstrates strong positivity for all patients with FA, with increased positivity for subsequent liver biopsies obtained for patients 1 and 2. (S-X) Cyclin-dependent kinase inhibitor 2A (p16) staining likewise shows widespread positivity centralized around the portal truads for all 3 patients with FA and is scantly positive in the FA control. (Y-DD) IHC for cytokeratin 7 (CK7) demonstrates moderate, widespread perivenular/hepatocyte and ductular staining in patients 1 and 2. Patient 3 had intermittent, mild staining for CK7. Magnification 40x throughout. Both positive and negative control tissue stained appropriately.
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References

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