RT Journal Article
SR Electronic
T1 The developmental stage of the hematopoietic niche regulates lineage in <em>MLL-</em>rearranged leukemia
JF The Journal of Experimental Medicine
JO J Exp Med
FD Rockefeller University Press
SP jem.20181765
DO 10.1084/jem.20181765
A1 Rowe, R. Grant
A1 Lummertz da Rocha, Edroaldo
A1 Sousa, Patricia
A1 Missios, Pavlos
A1 Morse, Michael
A1 Marion, William
A1 Yermalovich, Alena
A1 Barragan, Jessica
A1 Mathieu, Ronald
A1 Jha, Deepak Kumar
A1 Fleming, Mark D.
A1 North, Trista E.
A1 Daley, George Q.
YR 2019
UL http://jem.rupress.org/content/early/2019/02/05/jem.20181765.abstract
AB Leukemia phenotypes vary with age of onset. Delineating mechanisms of age specificity in leukemia could improve disease models and uncover new therapeutic approaches. Here, we used heterochronic transplantation of leukemia driven by MLL/KMT2A translocations to investigate the contribution of the age of the hematopoietic microenvironment to age-specific leukemia phenotypes. When driven by MLL-AF9, leukemia cells in the adult microenvironment sustained a myeloid phenotype, whereas the neonatal microenvironment supported genesis of mixed early B cell/myeloid leukemia. In MLL-ENL leukemia, the neonatal microenvironment potentiated B-lymphoid differentiation compared with the adult. Ccl5 elaborated from adult marrow stroma inhibited B-lymphoid differentiation of leukemia cells, illuminating a mechanism of age-specific lineage commitment. Our study illustrates the contribution of the developmental stage of the hematopoietic microenvironment in defining the age specificity of leukemia.