title: Identification of Flt3⁺CD150⁻ myeloid progenitors in adult mouse bone marrow that harbor T lymphoid developmental potential.
abstract: Common myeloid progenitors (CMPs) were first identified as progenitors that were restricted to myeloid and erythroid lineages. However, it was recently demonstrated that expression of both lymphoid- and myeloid-related genes could be detected in myeloid progenitors. Furthermore, these progenitors were able to give rise to T and B lymphocytes, in addition to myeloid cells. Yet, it was not known whether these progenitors were multipotent at the clonogenic level or there existed heterogeneity within these progenitors with different lineage potential. Here we report that previously defined CMPs possess T-lineage potential, and that this is exclusively found in the Flt3(+)CD150(-) subset of CMPs at the clonal level. In contrast, we did not detect B-lineage potential in CMP subsets. Therefore, these Flt3(+)CD150(-) myeloid progenitors were T/myeloid potent. Yet, Flt3(+)CD150(-) myeloid progenitors are not likely to efficiently traffic to the thymus and contribute to thymopoiesis under normal conditions because of the lack of CCR7 and CCR9 expression. Interestingly, both Flt3(+)CD150(-) and Flt3(-)CD150(-) myeloid progenitors are susceptible to Notch1-mediated T-cell acute lymphoblastic leukemia (T-ALL). Hence, gain-of-function Notch1 mutations occurring in developing myeloid progenitors, in addition to known T-lineage progenitors, could lead to T-ALL oncogenesis.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Anthony W S
authors.initials: AW
authors.lastname: Chi
authors.forename: Alejandro
authors.initials: A
authors.lastname: Chavez
authors.forename: Lanwei
authors.initials: L
authors.lastname: Xu
authors.forename: Brittany N
authors.initials: BN
authors.lastname: Weber
authors.forename: Olga
authors.initials: O
authors.lastname: Shestova
authors.forename: Andras
authors.initials: A
authors.lastname: Schaffer
authors.forename: Gerald
authors.initials: G
authors.lastname: Wertheim
authors.forename: Warren S
authors.initials: WS
authors.lastname: Pear
authors.forename: David
authors.initials: D
authors.lastname: Izon
authors.forename: Avinash
authors.initials: A
authors.lastname: Bhandoola
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D015153:Blotting, Western; D001853:Bone Marrow / Q000378:metabolism*; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D023461:Myeloid Progenitor Cells / Q000166:cytology* / Q000378:metabolism; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism; D051941:fms-Like Tyrosine Kinase 3 / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; C497762:Notch1 protein, mouse; D012333:RNA, Messenger; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; C497971:Flt3 protein, mouse; D051941:fms-Like Tyrosine Kinase 3; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse