The dark side of stemness – the role of hematopoietic stem cells in development of blood malignancies

Abstract

Hematopoietic stem cells (HSCs) produce all blood cells throughout the life of the organism. However, the high self-renewal and longevity of HSCs predispose them to accumulate mutations. The acquired mutations drive preleukemic clonal hematopoiesis, which is frequent among elderly people. The preleukemic state, although often asymptomatic, increases the risk of blood cancers. Nevertheless, the direct role of preleukemic HSCs is well-evidenced in adult myeloid leukemia (AML), while their contribution to other hematopoietic malignancies remains less understood. Here, we review the evidence supporting the role of preleukemic HSCs in different types of blood cancers, as well as present the alternative models of malignant evolution. Finally, we discuss the clinical importance of preleukemic HSCs in choosing the therapeutic strategies and provide the perspective on further studies on biology of preleukemic HSCs.

Latest Insights and Therapeutic Advances in Myelodysplastic Neoplasms

“…Myelodysplastic syndromes/neoplasms (MDSs) [1] encompass a diverse group of hematopoietic malignancies [1,2], often observed in the elderly [3]. They are characterized by recurrent molecular mutations [4][5][6], affecting the hematopoietic stem cell (HSC) compartment [7,8], and are often preceded by clonal haematopoiesis (CH), such as idiopathic dysplasia of unknown significance, clonal haematopoiesis of indeterminate potential, idiopathic cytopenia of uncertain significance, and cytopenia of undetermined significance (CCUS). Therefore, CH may represent premalignant conditions, as revealed by genomic analyses [8][9][10][11].…”