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Aberrant Stem Cell and Developmental Programs in Pediatric Leukemia

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Specialty Cell Biology
Date 2024 Apr 11
PMID 38601080
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Abstract

Hematopoiesis is a finely orchestrated process, whereby hematopoietic stem cells give rise to all mature blood cells. Crucially, they maintain the ability to self-renew and/or differentiate to replenish downstream progeny. This process starts at an embryonic stage and continues throughout the human lifespan. Blood cancers such as leukemia occur when normal hematopoiesis is disrupted, leading to uncontrolled proliferation and a block in differentiation of progenitors of a particular lineage (myeloid or lymphoid). Although normal stem cell programs are crucial for tissue homeostasis, these can be co-opted in many cancers, including leukemia. Myeloid or lymphoid leukemias often display stem cell-like properties that not only allow proliferation and survival of leukemic blasts but also enable them to escape treatments currently employed to treat patients. In addition, some leukemias, especially in children, have a fetal stem cell profile, which may reflect the developmental origins of the disease. Aberrant fetal stem cell programs necessary for leukemia maintenance are particularly attractive therapeutic targets. Understanding how hijacked stem cell programs lead to aberrant gene expression in place and time, and drive the biology of leukemia, will help us develop the best treatment strategies for patients.

References
1.
Porcher C, Chagraoui H, Kristiansen M . SCL/TAL1: a multifaceted regulator from blood development to disease. Blood. 2017; 129(15):2051-2060. DOI: 10.1182/blood-2016-12-754051. View

2.
Charbord P, Tavian M, Humeau L, Peault B . Early ontogeny of the human marrow from long bones: an immunohistochemical study of hematopoiesis and its microenvironment. Blood. 1996; 87(10):4109-19. View

3.
Bao S, Wu Q, McLendon R, Hao Y, Shi Q, Hjelmeland A . Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 2006; 444(7120):756-60. DOI: 10.1038/nature05236. View

4.
Abedin S, Badar T, Gauger K, Michaelis L, Runaas L, Carlson K . Safety and efficacy of pracinostat in combination with gemtuzumab ozogamicin (PraGO) in patients with relapsed/refractory acute myeloid leukemia. Leuk Res. 2022; 123:106984. DOI: 10.1016/j.leukres.2022.106984. View

5.
Bhansali R, Rammohan M, Lee P, Laurent A, Wen Q, Suraneni P . DYRK1A regulates B cell acute lymphoblastic leukemia through phosphorylation of FOXO1 and STAT3. J Clin Invest. 2021; 131(1). PMC: 7773384. DOI: 10.1172/JCI135937. View