Stem cell defects in patients with lymphoma (2019)

Abstract

Lymphoma is a cancer of the hematopoietic system and most patients respond to first-line treatment. However, a substantial fraction of patients experience relapse, severe treatment side effects and/or death due to lymphoma or therapy.

Hematopoietic stem cells (HSC) continuously give rise to all blood and lymphoid tissue in the human body. These stem cells can acquire DNA mutations which lead to a skewed formation of aberrant blood cells, called clonal hematopoiesis (CH). CH is a common age-related phenomenon. The occurrence and clinical consequences of these HSC defects in patients with lymphoma has so far only been sparsely investigated.

In the articles of this thesis we first reviewed the current knowledge on the origin of lymphomas. We furthermore identified HSC mutations, which were predominately known from CH, in 30.5% of patients with lymphoma. We investigated these mutations in a national population-based cohort of patients undergoing high-dose chemotherapy and found that mutations in genes of the DNA repair pathway were independently associated with inferior survival. Finally, we examined the development of CH mutations at several time points during treatment for mantle cell lymphoma. Mutated clones expanded rapidly during chemotherapy, but their growth declined after therapy.

In conclusion, this thesis contribute with knowledge regarding the clinical interplay of treatmen and HSC defects in patients with lymphoma.

Place of employment

PhD author

Simon Husby, cand.med.

Date and place of defense

30th August 2019, Auditorium 2, Rigshospitalet, Denmark

Supervisors

Professor Kirsten Grønbæk MD, DMSc
Associate professor Peter de Nully Brown, MD, PhD
Associate professor Jesper B. Andersen, PhD
Postdoc Christophe Côme, PhD

Assessment committee:
Professor Lena Specht, MD, DMSc (chair)
Professor Jude Fitzgibbon, BA, PhD
Professor Henrik Frederiksen, MD, PhD

Links

PubMed

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