Selective Autophagy in Normal and Malignant Hematopoiesis

Abstract The hierarchical organization of the hematopoietic system requires hematopoietic stem cells (HSCs) capable of self-renewal and multilineage differentiation to produce all cellular lineages of the blood. Novel techniques of purification of hematopoietic subpopulations and their functional characterization have defined individual steps of their lineage commitment. A detailed molecular map of the selective autophagy landscape governing self-renewal, maintenance, and differentiation of HSCs and their progeny during early and terminal differentiation has not yet been drawn. However, the importance of selective autophagy pathways is increasingly being recognized, as this evolutionary conserved degradation pathway is instrumental in orchestrating intracellular turnover of macromolecular complexes and organelles to meet the specific needs of various hematopoietic cells. For instance, mitophagy has clearly been demonstrated to regulate mitochondrial homeostasis in HSCs, thereby defining their metabolic fate decisions. This review focuses on the emerging evidence supporting an important role of selective autophagy in regulating normal hematopoiesis. As this has uncovered important features in malignant hematopoiesis, the review also covers aspects of selective autophagy pathways affected in the development and progression of leukemia and lymphoma. A molecular understanding of the unique requirements of selective autophagy may open new avenues for specific therapeutic intervention.