28 June 2021

Mutations known from B-cell lymphoid malignancies are not found in CD34+ stem cells from patients with lymphoma.

Husby, S., Favero, F., Rodriguez-Gonzalez, F. G., Sutton, L. A., Haastrup, E. K., Ørskov, A. D., Hansen, J. W., Arboe, B., Aslan, D., Clasen-Linde, E., Rahbek Gjerdrum, L. M., Gørlev, J. S., Brown, P., Fischer-Nielsen, A., Rosenquist, R., Weischenfeldt, J., and Grønbæk, K. (2021) Mutations known from B-cell lymphoid malignancies are not found in CD34+ stem cells from patients with lymphoma. Leukemia & Lymphoma, 1-4. doi: 10.1080/10428194.2021.1933473

Introduction

Autologous stem-cell transplantation (ASCT) consists of infusion of previously harvested CD34+ hematopoietic stem cells after high-dose chemotherapy. This treatment can be curative for patients with aggressive and/or relapsing lymphomas [1,2]; however, the mortality rate is at least 30% and is driven mainly by progressive disease, treatment toxicity, and severe infections. Factors that contribute to inferior survival after ASCT have been reported as primary refractory disease, higher age, aaIPI score (stage, LDH, performance status), and prolonged hospitalization [3,4]. Apart from progressive disease, the underlying biological cause of mortality following ASCT has until recently remained undescribed.

Somatic non-tumor mutations identified in the peripheral blood of both patients and healthy individuals, termed clonal hematopoiesis, are associated with adverse outcomes after chemotherapy [5,6]. These mutations are thought to arise in the hematopoietic stem and progenitor cells (HPSC’s, phenotypically identified by CD34+ expression) [7,8].

We here investigated genetic defects in CD34+ HSPC’s from lymphoma patients undergoing ASCT and correlated with clinical outcome. To also examine the existence of possible lymphoma stem cell populations, we analyzed genes known to be mutated in myeloid and lymphoid neoplasms.