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Biomedical subjects

P Nowell

Publications and source records attributed to P Nowell.

28 records · Page 2Linked to original sources
PubMed1981

Cytogenetic studies of bone marrow in breast cancer patients after adjuvant chemotherapy.

Bone marrow chromosome studies were done on three patients who developed acute nonlymphocytic leukemia 5 to 19 months after completion of adjuvant chemotherapy for breast cancer, and on 17 breast cancer patients without hematologic disease 2 to 30 months after similar adjuvant therapy. Clones of cells with multiple cytogenetic abnormalities were demonstrated in two of the three leukemic patients. No chromosomally abnormal clones or evidence of increased chromosome damage was found in the 17 nonleukemic individuals. Although leukemias induced by chemotherapy, and particularly by alkylating agents, typically show multiple cytogenetic alterations, it appears that patients recently exposed to these agents, but without obvious hematopoietic disorders, do not have a high frequency of aberrant marrow clones. Additional approaches may be needed for early identification of patients at increased risk for chemotherapy-induced leukemia.

Aged↗
PubMed1981

Proliferation, differentiation, and cytogenetics of chronic leukemic B lymphocytes cultured with mitomycin-treated normal cells.

Lymphocytes from 6 patients with chronic lymphocytic leukemia of the B-cell variety (B-CLL) were cultured with equal numbers of mitomycin-treated mononuclear cells from normal blood. When stimulated with pokeweed mitogen (PWM), phytohemagglutinin (PHA), or the tumor-promoting agent, phorbol tetradecanoyl-acetate (TPA), the CLL cells proliferated actively by day 3 or 4 of culture, and in four cases, differentiated to significant numbers of immunoglobulin-containing cells. Chromosome studies on the proliferating lymphocytes demonstrated a cytogenetically abnormal clone in three patients, including two with a 14q+ marker chromosome and two with a translocation involving the short arm of chromosome 9. One patient had a translocation from 22q to 14q, producing a Philadelphia chromosome as well as the 14q+ marker. The results indicate that the neoplastic lymphocytes of B-CLL may proliferate and differentiate when appropriately stimulated in vitro, and that chromosomally abnormal clones are not uncommon. With several techniques now available for successful short-term culture of B-CLL lymphocytes, there is opportunity for better understanding of the cellular alterations in this disease.

B-Lymphocytes↗
PubMed1981

Cytogenetic evidence for the clonal nature of Richter's syndrome.

Sequential chromosome studies were done on a patient who developed diffuse histiocytic lymphoma (DHL) after a long history of untreated chronic T-cell leukemia. During the indolent phase of her disease, a pseudodiploid lymphocyte population with 3q+ and 14q+ chromosome markers gradually replaced the originally diploid tumor cells. The karyotype of the lymphoma was hypertriploid (70--74 chromosomes) with the same 3q+ and 14q+ markers. The findings indicate that DHL in this patient evolved from the leukemic T-cell clone.

Clone Cells↗
PubMed1978

Cytogenetics of chronic T cell leukemia, including two patients with a 14q+ translocation.

Chromosome studies were done on 7 patients with chronic T cell leukemia. Their lymphocytes responded in culture to one or more T cell mitogens: PHA, Con A, or the calcium ionophore A23187. Clones of cytogenetically-abnormal cells were present in all seven patients, but on occasion the frequency of such cells varied greatly in cultures stimulated with different mitogens. There was no consistent chromosome change, but alterations of chromosome 2 were noted in four individuals and of chromosome 14 in three. In two patients, there was a translocation to the long arm of chromosome 14, producing a 14q+, with the break point in the terminal portion, an abnormality previously observed in B cell lymphomas. One of these patients also showed evidence of clonal evolution in sequential cytogenetic studies, but more data are needed to determine whether such investigations are of prognostic value with respect to the clinical course of the disease.

Adult↗
PubMed1978

Chromosome studies in preleukemic states. IV. Myeloproliferative versus cytopenic disorders.

The prognostic value of marrow chromosome studies was examined in 112 "preleukemic" patients followed for at least one year or until death. Based on recent definitions, 49 patients were classified as myeloproliferative disorders (MPD) (polycythemia vera, myelofibrosis, undifferentiated myeloproliferative disorder, essential thrombocythemia), and 58 as cytopenic states (refractory anemia, pancytopenia). In each group, approximately one-third had a chromosomally-abnormal clone. For MPD, this had little predictive value, but in the cytopenias, 77% with a cytogenetic abnormality developed leukemia versus 39% without. Twelve cytopenic patients had multiple alterations involving more than 2 chromosomes and 11 died within 6 months, 9 with leukemia. Such patients may warrant consideration for aggressive chemotherapy before the appearance of clinical leukemia. Banding studies did not reveal any specific chromosome abnormalities consistently associated with these various preleukemic disorders, or with progression to leukemia, but nonrandom alterations were noted involving chromosomes 1, 5, 7-9, and 20 in the MPD group, and chromosomes 6 and 16 in the cytopenic patients. Correlation of these data with other reports indicates that certain cytogenetic abnormalities involving specific segments of the human genome confer a selective growth advantage on hemic clones which may present clinically as either preleukemia or leukemia.

Adult↗
PubMed1977

The mitogenic effect of A23187 in human peripheral lymphocytes.

The mitogenic action of the divalent ionophore A23187 was confirmed and shown to be very sensitive to changes in extracellular calcium ion concentration. At optimal calcium and ionophore concentrations, an increase in [3H]-thymidine incorporation was seen that was similar to that seen after phytohemagglutinin addition. A calcium-dependent stimulation of alpha-aminoisobutyric acid transport was also seen after A23187 addition. Studies with three inhibitors demonstrate a similarity between proliferation induced by phytohemagglutinin and by A23187. Isoproterenol (10(-4) M) and ouabain (10(-7) M) blocked the effects of phytohemagglutinin and A23187. A drug, D-600 that has been shown to block calcium channels in cardiac muscle, inhibited proliferation induced by either phytohemagglutinin or A23187. This concentration of D600 had no effect on either phytohemagglutinin- or A23187-induced 45Ca2+ uptake. Furthermore, the (+) and (-) isomers separated from racemic D600, which have been shown to block sodium and calcium channels respectively in smooth muscle, had equal potency in blocking lymphocyte proliferation.

Aminoisobutyric Acids↗
PubMed1976

Chromosome studies in "preleukemia". III. Myelofibrosis.

Cytogenetic studies were done on 18 patients with myelofibrosis or the closely related syndrome, undifferentiated myeloproliferative disorder (MPD). Clones of cells with chromosome abnormalities were demonstrated in the blood of eight individuals, including two with a history of radiation therapy and two with "acute myelofibrosis". Trisomy 8 was present in the latter two patients, but otherwise, there was no consistent cytogenetic pattern or correlation with specific hematologic findings. Sixteen of these patients have been followed for more than 1 year or until death; none has progressed to leukemia. The results indicate that chromosome abnormalities are relatively common in this disorder, but as with polycythemia vera, and unlike some other "preleukemic" states, the aberrant clones in myelofibrosis do not appear to indicate that clinical leukemia is imminent.

Adolescent↗
PubMed1976

T cell variant of chronic lymphocytic leukaemia with chromosome abnormality and defective response to mitogens.

Lymphocytes from a patient with chronic lymphocytic leukaemia, in whom therapy was ineffective, were defined as thymus-derived (T) cells by membrane markers (sheep erythrocyte rosettes, complement rosettes, surface immunoglobulin). The lymphocytes responded weakly to two mitogens, phytohaemagglutinin and the calcium ionophore A23187, but not to concanavalin A. Cytogenetic studies of leukaemic cells from unstimulated and mitogen-stimulated cultures revealed an abnormal karyotype with 45 chromosomes and multiple rearrangements. The T cell variant of classical chronic lymphocytic leukaemia is relatively rare; additional reports are needed to determine if the clinical course is typically less benign than in the common B cell variety, or whether this patient simply represented a late, unresponsive phase of the disease.

Aged↗
PubMedDate not supplied

Association of amplified oncogene c-myc with an abnormally banded chromosome 8 in a human leukaemia cell line.

Several unusual chromosome structures have been described in drug-resistant cell lines and in certain tumours. These structures include elongated homogeneously staining regions (HSRs), small extrachromosomal paired chromatin bodies (double minutes, DMs) and abnormally banded regions (ABRs) with strong but anomalous band patterns. There is evidence that these are alternative forms of gene amplification, with HSRs breaking down to form DMs, and DMs integrating into the chromosome to generate HSRs and ABRs. Recently, it was demonstrated that, compared with several normal and leukaemia human cells, DNA sequences representing the human homologue of the onc gene of the avian myelocytomatosis virus (MC29), the so-called c-myc gene, were amplified in HL-60 cells. This is a human promyelocytic leukaemia cell line established in the laboratory of one of us (R.C.G.) at the National Cancer Institute (Bethesda, Maryland) in 1977, and widely used for studies on myeloid and monocytic differentiation. Amplification of the gene was present in primary leukaemic cells of the patient, and DMs were noted in some of these cells as well as in early passages of the HL-60 line. No structure resembling HSRs or ABRs were noted in karyotypic studies at this early stage and there were no alterations involving the long arm of chromosome 8 (8q), to which the c-myc gene has recently been mapped. We have now re-examined the karyotype of the HL-60 line, using cells frozen at various times during its continuous passage at the Wistar Institute (Philadelphia, Pennsylvania) to look for chromosomal abnormalities that might be associated with the amplification of c-myc. We find that, beginning in 1979, HL-60 cells at the Wistar Institute no longer had DMs, but did show an abnormal 8q+ chromosome, replacing a normal chromosome 8, and representing an ABR reflecting the site of myc gene amplification.

Cell Line↗