Tags

Type your tag names separated by a space and hit enter

Autocrine and paracrine effects of an ES-cell derived, BCR/ABL-transformed hematopoietic cell line that induces leukemia in mice.
Oncogene 2001; 20(21):2636-46O

Abstract

During differentiation in vitro, Embryonic Stem (ES) cells generate both primitive erythroid and definitive myeloid lineages in a process that mimics hematopoiesis in the mammalian yolk sac. To investigate leukemic transformation of these embryonic hematopoietic progenitors, we infected differentiating cultures of ES cells with the Chronic Myeloid Leukemia-specific BCR/ABL oncoprotein. Following a period of liquid culture, we isolated two transformed subclones, EB57 and EB67, that retained characteristics of embryonic hematopoietic progenitors and induced a fatal leukemia in mice characterized by massive splenomegaly and granulocytosis. Histopathology of the spleen revealed an abundance of undifferentiated blast-like cells. Investigation of the clonal origins of the granulocytes in the peripheral blood demonstrated that the injected donor cells contributed modestly to the granulocyte population while the majority were host-derived. EB57 secretes IL-3 and unidentified cytokines that can stimulate autocrine and paracrine cell proliferation, presumably accounting for the reactive granulocytosis in diseased mice. These BCR/ABL transformed hematopoietic derivatives of ES cells recapitulate the relationship of BCR/ABL expression to IL-3 production that has been described for primitive hematopoietic progenitors from human CML patients, and illustrates the potential for autocrine and paracrine effects of BCR/ABL-infected cells in murine models.

Authors+Show Affiliations

Whitehead Institute, 9 Cambridge Center, Cambridge, Massachusetts, MA 02142, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11420675

Citation

Peters, D G., et al. "Autocrine and Paracrine Effects of an ES-cell Derived, BCR/ABL-transformed Hematopoietic Cell Line That Induces Leukemia in Mice." Oncogene, vol. 20, no. 21, 2001, pp. 2636-46.
Peters DG, Klucher KM, Perlingeiro RC, et al. Autocrine and paracrine effects of an ES-cell derived, BCR/ABL-transformed hematopoietic cell line that induces leukemia in mice. Oncogene. 2001;20(21):2636-46.
Peters, D. G., Klucher, K. M., Perlingeiro, R. C., Dessain, S. K., Koh, E. Y., & Daley, G. Q. (2001). Autocrine and paracrine effects of an ES-cell derived, BCR/ABL-transformed hematopoietic cell line that induces leukemia in mice. Oncogene, 20(21), pp. 2636-46.
Peters DG, et al. Autocrine and Paracrine Effects of an ES-cell Derived, BCR/ABL-transformed Hematopoietic Cell Line That Induces Leukemia in Mice. Oncogene. 2001 May 10;20(21):2636-46. PubMed PMID: 11420675.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Autocrine and paracrine effects of an ES-cell derived, BCR/ABL-transformed hematopoietic cell line that induces leukemia in mice. AU - Peters,D G, AU - Klucher,K M, AU - Perlingeiro,R C, AU - Dessain,S K, AU - Koh,E Y, AU - Daley,G Q, PY - 2000/09/29/received PY - 2001/01/30/revised PY - 2001/02/12/accepted PY - 2001/6/23/pubmed PY - 2001/7/6/medline PY - 2001/6/23/entrez SP - 2636 EP - 46 JF - Oncogene JO - Oncogene VL - 20 IS - 21 N2 - During differentiation in vitro, Embryonic Stem (ES) cells generate both primitive erythroid and definitive myeloid lineages in a process that mimics hematopoiesis in the mammalian yolk sac. To investigate leukemic transformation of these embryonic hematopoietic progenitors, we infected differentiating cultures of ES cells with the Chronic Myeloid Leukemia-specific BCR/ABL oncoprotein. Following a period of liquid culture, we isolated two transformed subclones, EB57 and EB67, that retained characteristics of embryonic hematopoietic progenitors and induced a fatal leukemia in mice characterized by massive splenomegaly and granulocytosis. Histopathology of the spleen revealed an abundance of undifferentiated blast-like cells. Investigation of the clonal origins of the granulocytes in the peripheral blood demonstrated that the injected donor cells contributed modestly to the granulocyte population while the majority were host-derived. EB57 secretes IL-3 and unidentified cytokines that can stimulate autocrine and paracrine cell proliferation, presumably accounting for the reactive granulocytosis in diseased mice. These BCR/ABL transformed hematopoietic derivatives of ES cells recapitulate the relationship of BCR/ABL expression to IL-3 production that has been described for primitive hematopoietic progenitors from human CML patients, and illustrates the potential for autocrine and paracrine effects of BCR/ABL-infected cells in murine models. SN - 0950-9232 UR - https://www.unboundmedicine.com/medline/citation/11420675/Autocrine_and_paracrine_effects_of_an_ES_cell_derived_BCR/ABL_transformed_hematopoietic_cell_line_that_induces_leukemia_in_mice_ L2 - http://dx.doi.org/10.1038/sj.onc.1204374 DB - PRIME DP - Unbound Medicine ER -