Dissecting Clonal Hematopoiesis in Tissues of Classical Hodgkin Lymphoma Patients

• Published in: Blood cancer discovery Vol. 2; no. 3; pp. 216 - 225
• Main Authors: Venanzi, Alessandra, Marra, Andrea, Schiavoni, Gianluca, Milner, Sara G, Limongello, Roberto, Santi, Alessia, Pettirossi, Valentina, Ultimo, Simona, Tasselli, Luisa, Pucciarini, Alessandra, Falini, Lorenza, Sciabolacci, Sofia, Martelli, Maria Paola, Sportoletti, Paolo, Ascani, Stefano, Falini, Brunangelo, Tiacci, Enrico
• Format: Journal Article
• Language: English
• Published: United States 01.05.2021
• Subjects: Clonal Hematopoiesis - genetics; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Hodgkin Disease - genetics; Humans; Mutation; Tumor Microenvironment; NPM1; Microenvironment; Acute myeloid leukemia; Clonal hematopoiesis; DNMT3A; Hodgkin lymphoma
• ISSN: 2643-3249
• DOI: 10.1158/2643-3230.BCD-20-0203

Clonal hematopoiesis predisposes to hematological malignancies. However, clonal hematopoiesis is understudied in classical Hodgkin lymphoma (cHL), a mature B-cell neoplasm exhibiting the most abundant microenvironment. We analyzed clonal hematopoiesis in 40 cHL cases by sequencing microdissected tumor cells and matched normal cells from blood and/or lymph nodes. Five patients had blood and/or tissue clonal hematopoiesis. In three of five patients (all failing first-line therapy), clonal hematopoiesis spread through the tissue microenvironment extensively, and featured mutant , and + * in 33%, 92% and 60% of non-neoplastic cells, respectively. In the latter case, mutant clonal hematopoiesis seeded the neoplastic clone, which was infected by the Epstein-Barr virus and showed almost no other somatic mutations exome-wide. In the former case, -mutant clonal hematopoiesis did not originate the neoplastic clone despite dominating the blood and B-cell lineage (~94% leukocytes; ~96% mature blood B cells), yet led to -mutated acute myeloid leukemia 6 years after therapy for cHL. Our results expand to cHL the spectrum of hematologic malignancies associated with clonal hematopoiesis.