Biomedical subjects

P A Downie

Publications and source records attributed to P A Downie.

At least 19 recordsLinked to original sources

PubMed1997

Growth inhibition of B-cell precursor acute lymphoblastic leukemia cell lines by monocytes: a role for prostaglandin E2.

Leukemic cell lines have proven invaluable in the molecular analysis of recurring chromosomal translocations but the optimal methods for leukemia cell line establishment are unknown. During in vitro culture, most B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells die within 1 week at least partially mediated by inhibitors elaborated by peripheral blood mononuclear cells (PB MNCs) present within the leukemia sample. In experiments reported here, cyclooxygenase inhibitors (indomethacin and meclofenamic acid) blocked the PB MNC-mediated inhibition of BCP-ALL proliferation. Also, prostaglandin E2 (PGE2) was detected in supernatants from PB MNC cultures. When PGE2 was mixed directly with BCP-ALL cells, proliferation decreased significantly. Under the culture conditions used, PB MNCs secreted PGE2 which appears to be one of the major inhibitors of BCP-ALL growth in vitro.

Adult↗

PubMed1994

Establishment of a leukemia cell line with i(12p) from a patient with a mediastinal germ cell tumor and acute lymphoblastic leukemia.

We report the establishment of a leukemia cell line (UoC-B10) from a patient who developed leukemia several months after the diagnosis of a mediastinal yolk sac tumor. The patient's yolk sac tumor responded to combination chemotherapy, and a mature teratoma with focal areas of hematopoiesis was subsequently resected. However, 5 months after the initial diagnosis, the patient developed an acute lymphoblastic leukemia with a precursor B-cell phenotype. Cytogenetic analysis showed an i(12p) abnormality in the patient's leukemia cells and in the UoC-B10 cell line. The i(12p) was also identified retrospectively in the mediastinal tumor cells by fluorescent in situ hybridization analysis. The UoC-B10 cell line, which has been growing continuously for > 24 months in culture, was Epstein-Barr virus negative and was generally concordant with the patient's leukemia cells by analysis of immunophenotype, karyotype, and genotype. The UoC-B10 cell line possesses receptors for granulocyte-colony-stimulating factor, a cytokine which the patient received as part of his treatment protocol. This cell line may be useful in studying the relationship between i(12p) and hematological differentiation of human mediastinal germ cell tumors.

Adult↗

PubMed1993

Establishment of cell lines from B-cell precursor acute lymphoblastic leukemia.

In an attempt to establish permanent cell lines from children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL), 123 clinical samples from 117 patients were cultured in vitro. Using a method which was successful for the growth of ALL with T-cell phenotype, 3% (2/74) of BCP-ALL samples from patients at diagnosis and 31% (9/29) of BCP-ALL samples from patients at relapse were established as cell lines. However, in most cultures, leukemic cells survived for only a few weeks and the majority of viable cells present after 28 days of culture were esterase-positive mononuclear cells. Based on the hypothesis that mononuclear cells inhibited leukemic cell growth, we evaluated the effect of a monocyte toxin, L-leucine methyl ester (Leu-OMe), on the growth of four frozen BCP-ALL samples. Thawed leukemic cells treated with Leu-OMe, but not untreated control cells, proliferated in three samples and one new cell line was established. Subsequently, when Leu-OMe was added to fresh leukemia cells in culture, leukemic cell lines were grown from 29% (4/14) of samples at diagnosis and 66% (4/6) of relapse samples. Overall, 20 BCP-ALL cell lines were established, all were Epstein-Barr virus (EBV)-negative, and authenticity of each cell line was verified by a direct comparison of the immunophenotype, karyotype, and genotype with the patient's tumor cells. This improved method of cell culture permits a higher success rate of cell line establishment from patients with BCP-ALL thereby aiding in analysis of B-lymphocyte transformation and neoplasia.

Adolescent↗

PubMed1981