Absence of negative growth regulation in three new murine radiation-induced myeloid leukemia cell lines with deletion of chromosome 2.
Murine radiation-induced acute myeloid leukemia (RI-AML) may be considered as the experimental counterpart of human secondary leukemia. Three new myelomonocytic cell lines derived from RI-AML and carrying a partially deleted chromosome 2 are described. The RI-AML cells responded with increased proliferation after being incubated with the hemopoietic growth factors rG-CSF, rGM-CSF and IL-3. Increased proliferation of the same extent without any effect in differentiation, was also demonstrated in the RI-AML cells after incubation with IL-6 and with mouse lung conditioned medium (CM) and Krebs ascites tumor cells CM which induce differentiation in normal and most leukemic myeloid cells. Down-regulation of the c-myc gene and induction of (2'-5') oligo-adenylate synthetase (reflecting autocrine interferon secretion), two essential mechanisms operating during arrest of growth and concomitant differentiation, were demonstrated to be absent in RI-AML cells. In contrast, the M1 cells responded to the above differentiating factors with growth arrest and differentiation and with appropriate c-myc down-regulation and synthetase induction. The genetic basis for the distinct RI-AML cells' behavior may be connected with the loss or structural and/or functional abnormalities of DNA sequences located in the deleted part of chromosome 2 or in the respective allele. The presently described new RI-AML cell lines may be used for studies concerning myeloid leukemogenesis in general and secondary leukemia in particular.
Resnitzky
P
P
Department of Medicine B, Kaplan Hospital, Rehovot, Israel.
Goren
T
T
Shaft
D
D
Trakhtenbrot
L
L
Peled
A
A
Resnitzky
D
D
Zipori
D
D
Haran-Ghera
N
N
D015088:2',5'-Oligoadenylate Synthetase / Q000032:analysis; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002872:Chromosome Deletion; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D007953:Leukemia, Radiation-Induced / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis*; D012334:RNA, Neoplasm / Q000032:analysis*; D014407:Tumor Cells, Cultured
D016271:Proto-Oncogene Proteins c-myc; D012334:RNA, Neoplasm; D015088:2',5'-Oligoadenylate Synthetase