1. Dissecting Clonal Hematopoiesis in Tissues of Classical Hodgkin Lymphoma Patients
- Author
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Alessandra, Venanzi, Marra, Andrea, Gianluca, Schiavoni, Sara, G Milner, Limongello, Roberto, Santi, Alessia, Pettirossi, Valentina, Simona, Ultimo, Tasselli, Luisa, Alessandra, Pucciarini, Falini, Lorenza, Sciabolacci, Sofia, Martelli, Maria Paola, Sportoletti, Paolo, Ascani, Stefano, Falini, Brunangelo, and Tiacci, Enrico
- Subjects
Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,Acute myeloid leukemia ,Microenvironment ,Hodgkin Disease ,Article ,Mutation ,Tumor Microenvironment ,DNMT3A ,Humans ,NPM1 ,Clonal Hematopoiesis ,Hodgkin lymphoma ,Clonal hematopoiesis - Abstract
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 DNMT3A(R882H), KRAS(G60D) and DNMT3A(R882H)+TET2(Q1274)* in 33%, 92% and 60% of non-neoplastic cells, respectively. In the latter case, DNMT3A/TET2-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, DNMT3A-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 NPM1-mutated acute myeloid leukemia 6 years after therapy for cHL. Our results expand to cHL the spectrum of hematologic malignancies associated with clonal hematopoiesis.
- Published
- 2021