Phorbol ester tumor promoters block the transition from the early to the heme‐dependent late program of friend cell differentiation

Mager, Dixie L.; Bernstein, Alan

doi:10.1002/jcp.1041050316

Cited by 10 publications

(2 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A comparison of the spontaneous differentiation and self-renewal probabilities of CFU-FV-A and CFU-FV-P suggested that there is an inverse relationship between the proliferative and developmental capacities of these CFU-FV. This conclusion is consistent with findings on the relationship between the colony-forming ability and the extent of differentiation of permanent erythroid cell lines transformed by Friend virus (30).…”

Section: Discussionsupporting

confidence: 92%

Clonal analysis of the late stages of erythroleukemia induced by two distinct strains of Friend leukemia virus.

et al. 1981

View full text Add to dashboard Cite

We observed striking differences between the tumorigenic colony-forming cells present in the spleens of mice late after infection with the anemia-inducing strain of Friend leukemia virus (strain FV-A) and those present after infection with the polycythemia-inducing strain (strain FV-P). Cells within primary colonies derived from FV-A-and FV-P-transformed cells (CFU-FV-A and CFU-FV-P, respectively) contained hemoglobin and spectrin, indicating that the CFU-FV-A and CFU-FV-P were transformed erythroid progenitor cells. The proportion of cells containing hemoglobin was relatively high (>25%) in newly isolated cell lines , derived from CFU-FV-P colonies, whereas cell lines derived from CFU-FV-A colonies had only low levels (O to 2%) of hemoglobin-containing cells. A high proportion of the cell lines derived from CFU-FV-A colonies responded to pure erythropoietin and accumulated spectrin and hemoglobin, whereas the cell lines derived from CFU-FV-P colonies did not. A cytogenetic analysis indicated that primary CFU-FV-P colony cells were diploid, whereas chromosomal aberrations were observed in the immediate progeny of CFU-FV-A. The presence of unique chromosomal markers in the majority of the cells within individual colonies derived from CFU-FV-A suggested that these colonies originated from single cells. Finally, leukemic progenitor cells transformed by strain FV-A appeared to have an extensive capacity to self-renew (i.e., form secondary colonies in methylcellulose), whereas a significant proportion of the corresponding cells transformed by strain FV-P did not. In addition, the self-renewal capacity of both CFU-FV-A and CFU-FV-P increased as the disease progressed. From these observations, we propose a model for the multistage nature of Friend disease; this model involves clonal evolution and expansion from a differentiating population with limited proliferative capacity to a population with a high capacity for selfrenewal and proliferation.Two distinct isolates of Friend leukemia virus have been described, and both of these isolates induce rapid splenomegaly and erythroleukemia in susceptible adult mice. The original isolate (strain FV-A) (11) induces anemia, whereas the later isolate (strain FV-P), which was derived from stocks of FV-A (38), induces polycythemia. In addition to these opposite effects on the levels of erythrocytes in the peripheral blood, the diseases induced by FV-A and FV-P can be distinguished by the different responses of erythroid progenitor cells to the hormnone erythropoietin (Epo). Erythropoiesis in FV-A-infected mice appears to remain under the control of Epo in vivo (49), whereas erythropoiesis in FV-P-infected t Present address:

show abstract

Section: Discussionsupporting

confidence: 92%

Clonal analysis of the late stages of erythroleukemia induced by two distinct strains of Friend leukemia virus.

et al. 1981

View full text Add to dashboard Cite

show abstract

“…Since differentiation-related, in contrast to inducer-related, slowing of cell proliferation occurred only after the cells accumulated haemoglobin, it might be argued that the accumulation of the maturation-specific products is responsible for the loss of the multiplication potential. This conclusion is backed by studies indicating the essential role for haem synthesis in the commitment to terminal cell division (Mager et al, 1979(Mager et al, , 1980. However, other studies have indicated that terminal cell division and the co-ordinated expression of the inducer-mediated differentiation products are not necessarily linked.…”

Section: Discussionmentioning

confidence: 99%

Analysis of the growth kinetics of murine erythroleukaemia cells following commitment to terminal differentiation

Fibach

1987

Cell Proliferation

View full text Add to dashboard Cite

Differentiation of murine erythroleukaemia cells by various inducers involves a step of irreversible commitment, after which the presence of the inducer is not required for completion of the process. Some cells become partially committed and give rise to differentiated as well as undifferentiated progeny. Commitment occurs asynchronously; under suboptimal inducing conditions, such as low concentration of inducer or short duration of exposure, both committed and uncommitted cells co-exist. In the present study the growth of these subpopulations was compared. Murine erythroleukaemia cells were exposed to the inducer hexamethylene-bisacetamide for 24 hr, then the inducer was removed by washing and the rate of proliferation of committed and uncommitted cells was measured. Commitment was scored by cloning the cells in inducer-free semi-solid medium and determining the cellular composition of the colonies with respect to haemoglobin content. The results indicated that following removal of the inducer the rate of proliferation was retarded similarly for both committed and uncommitted cells. Partially committed cells disappeared rapidly due to assymetrical cell division into fully committed and uncommitted cells. Both committed and uncommitted cells resumed logarithmic growth at 53 hr, but while uncommitted cells continued this pace until saturation was achieved, committed cells stopped multiplying earlier as a result of terminal differentiation.

show abstract

Dissociation of hemoglobin accumulation and commitment during murine erythroleukemia cell differentiation by treatment with imidazole

Gusella

Tsiftsoglou

Volloch

et al. 1982

Journal Cellular Physiology

View full text Add to dashboard Cite

The effect of imidazole on DMSO-induced murine erythroleukemia (MEL) cell differentiation has been examined. While imidazole does inhibit heme, globin mRNA, and hemoglobin accumulation in DMSO-induced MEL cells, it does not affect the commitment of MEL cells to the specific limitation of proliferative capacity associated with the in vitro differentiation program. Furthermore, imidazole treatment does not affect DMSO-induced changes in cell volume, in the relative proportion of nuclear protein IP25, and in the specific activity of the enzyme cytidine deaminase. A clonal analysis in the presence of imidazole indicated that the drug prevents heme accumulation even in MEL cells already committed to terminal differentiation. These observations suggest that imidazole effectively dissociates two aspects of the erythroid differentiation program of MEL cells: globin gene expression and commitment to loss of proliferative capacity.

show abstract

Phorbol ester tumor promoters block the transition from the early to the heme‐dependent late program of friend cell differentiation

Cited by 10 publications

References 33 publications

Clonal analysis of the late stages of erythroleukemia induced by two distinct strains of Friend leukemia virus.

Clonal analysis of the late stages of erythroleukemia induced by two distinct strains of Friend leukemia virus.

Analysis of the growth kinetics of murine erythroleukaemia cells following commitment to terminal differentiation

Dissociation of hemoglobin accumulation and commitment during murine erythroleukemia cell differentiation by treatment with imidazole

Contact Info

Product

Resources

About