Cultures of permanent lines of human promyelocytic cells and the

Details Cultures of permanent lines of human promyelocytic cells and the Cultures of permanent lines of human promyelocytic cells and the

1993-12-17

1996-12-31

Scheiner, Toni R.

Chemistry: molecular biology and microbiology

Measuring or testing process involving enzymes or...

Involving antigen-antibody binding, specific binding protein...

435 6, 4352402, 436 63, 436 64, 436813, G01N 33574, C12N 508

Patent

active

055893457

DESCRIPTION:

BRIEF SUMMARY
This application was filed under 35 U.S.C. 371 as the national stage of PCT/FR92/00173 filed Feb. 25, 1992, and published as WO92/14815 Sep. 3, 1992.
Acute promyelocytic leukemia (or APL or also leukemia type 3) is a well-defined variety of leukemia, and is cytogenetically characterized by a translocation t (15; 17) (q22; q11-12) (Rowley J. D. et al., Lancet 1:549, 1977). This translocation could play a role in the uncontrolled cellular proliferation with blockage of cell maturation which occurs in APL.
In vitro and in vivo studies have made it possible to demonstrate that retinoic acid (also designated hereafter as RA) stops the process of cellular proliferation of the APL and induces the morphological and functional maturation of the promyelocytes towards the granulocyte stage.
This effect of retinoic acid on the promyelocytes suggests that the expression of certain genes intimately implicated in the transduction of the RA signal or in the process of maturation of the cells is adversely affected by the translocation mentioned above.
In vitro studies conducted on promyelocytes derived from patients suffering from APL have made it possible to demonstrate that the gene coding for the alpha receptor of retinoic acid (RAR.alpha. receptor) normally located on chromosome 17 has been rearranged by translocation with the PML locus normally located on chromosome 15 (de The et al., Nature, 347, pp558-561, 1990). By using probes corresponding to segments of DNA localized in the vicinity of the breaking points of the translocation, it was possible to define genomic rearrangements of one or other locus in the patients suffering from APL mentioned above. Consequently, the RAR.alpha. and PML genes are rearranged in the APLs. These experiments strongly support the implication of the alpha receptor of retinoic acid in acute promyelocytic leukemias.
In the light of the importance of the role played by the RAR.alpha. in the pathology of the APLs, it would be particularly interesting to be able to have available cell lines constituted of promyelocytes of human origin which have this translocation t (15; 17) characteristic of the APLs in order in particular to screen molecules derived from retinoic acid, or other molecules capable of restoring cell maturation without nonetheless exhibiting the toxic effects of retinoic acid.
However, it has hitherto not been possible to maintain a line of human promyelocytic cells in culture and, consequently, it has not been possible to perform this type of study.
Although the HL60 line has been called "promyelocytic" (Gallagher R. et al., Blood 54:713, 1979), it was subsequently recognized that, on the one hand, it is derived from a myeloblastic leukemia characterized by cells with a certain degree of maturation (M2) (Dalton W. T. et al., Blood 71; 242, 1988) and, on the other, it does not contain the above-mentioned translocation t (15; 17).
One of the objectives of the present invention is precisely that of making available a cell culture which permits the screening of molecules capable of restoring cellular maturation.
The subject of the present invention is permanent cell lines, characterized in that they are constituted essentially of promyelocytic cells characteristic of acute human promyelocytic leukemias, these cells being cytogenetically characterized by a translocation t (15; 17), and capable of proliferating indefinitely in a culture medium.
The culture medium in which the above-mentioned cells are capable of proliferating is advantageously constituted by a synthetic nutrient medium (RPMI 1640) and fetal calf serum.
The cell lines of the invention and their variants are characterized particularly in that they possess DNA fingerprints on gel electrophoresis identical, wholly or in part, with the DNA fingerprint shown in FIG. 1.
As an illustration, the DNA fingerprints of the cells constituting the cell lines of the invention are obtained by the procedure defined in Nucleic Acids Research (1988), vol. 16, No. 9, p. 4161.
The cell lines of the invention are advantageously characteri

REFERENCES:
Gianni et al, Blood 83 (7). 1994. 1909-1921 (abstract only).
Gallagher et al., "Characterization of the Continuous, Differentiating Myeloid Cell Line (HL-60) From a Patient with Acute Promyelocytic Leukemia", Blood, 54, 713-733 (1979).
Maizumi et al., "Retinoic Acid-Induced Monocytic Differentiation of HL60-MRI a Cell Line Derived From a Transplantable HL60 Tumor", Biosis Database Accession No. 83109596 (1987).

Affiliated with

Also associated with

Rating

Cultures of permanent lines of human promyelocytic cells and the does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Cultures of permanent lines of human promyelocytic cells and the, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Cultures of permanent lines of human promyelocytic cells and the will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-1141281