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J Melle

Publications and source records attributed to J Melle.

22 records · Page 2Linked to original sources

Cyclin A expression in human hematological malignancies: a new marker of cell proliferation.

Several in vitro studies have shown that the cyclin A gene is expressed and plays an important role in both the S and G2-M phases of the cell cycle. We analyzed cells from the blood and bone marrow of patients with various, mostly neoplastic, hematological disorders to determine whether (a) the cyclin A protein level correlated with that of cyclin A RNA and (b) cell distribution among the different phases of the cell cycle correlated with cyclin A RNA expression. Thirty-eight patients were studied by means of dot blot and Western blot techniques for cyclin A RNA and protein accumulation, and 21 were also studied for cell cycle distribution by using flow cytometric analysis. Semiquantitative studies were based on densitometric computerized evaluation of dot and Western blots. There was a very strong positive correlation between cyclin A RNA and protein expression (r = 0.99; P < 0.00005), indicating that cyclin A accumulation is regulated in these cells at a transcriptional level. There was also a highly significant positive correlation between cyclin A RNA expression and the cumulative percentage of cells in S plus G2-M phase (r = 0.98; P < 0.00005). Therefore, this in vivo study shows that the expression of cyclin A RNA and protein in human hematological malignancies correlates with the percentage of cells in S plus G2-M phase and identifies cyclin A as a new potential cell proliferation index in oncology.

Cell Cycle↗

Contamination of peripheral blood by monoclonal B cells following treatment of multiple myeloma by high-dose chemotherapy.

Peripheral blood samples obtained from five patients with multiple myeloma, after high-dose chemotherapy, were studied for monoclonal B plasma cell contamination. We used the technique of immunoglobulin heavy chain gene 'fingerprinting' at the time of diagnosis and during apheresis. The level of sensitivity of this technique is between 0.01% and 0.001% in two patients in whom a monoclonal population was detected in peripheral blood.

Antineoplastic Combined Chemotherapy Protocols↗

Selective increase of alternatively spliced Lck transcripts from the proximal promotor in hematopoietic malignancies.

Screening by Northern blot for lck expression in 51 patients with diverse hematologic diseases has shown, for four of them, a 3 to 15-fold increase in the level of lck mRNA when compared with expression in healthy donors. These patients suffered from diverse malignancies: one Burkitt lymphoma, one T-cell lymphoma and two non-Hodgkin B-cell lymphoma. Specific analysis of the different lck transcripts in these patients by polymerase chain reaction and their relative quantitation demonstrate a significant increase of only the type IB and the type IC lck transcripts arising from the proximal promotor. Our study shows: (a) a high lck expression may occur in diverse hematologic diseases, (b) whatever the type of malignancy, this high expression results in a specific increase of the spliced transcripts arising only from the proximal promotor, and (c) in these four patients without any rearrangement or amplification, the high lck expression probably results from the specific activation of the proximal promotor.

Blotting, Northern↗

Evi-1 expression in leukemic patients with rearrangements of the 3q25-q28 chromosomal region.

The Evi-1 zinc-finger protein gene is normally not expressed in hematopoietic cells. However, high Evi-1 mRNA expression has been reported in mouse myeloblastic leukemias, due to transcriptional activation by proviral integration in either the Fim-3 or Evi-1 loci. The human Evi-1 gene is located on chromosome 3q24-q28. In this paper three examples are presented of human acute myelogenous leukemias presenting common characteristics: (i) high Evi-1 mRNA expression; (ii) chromosomal abnormalities t(3;3)(q21;q26) or inv(3;3)(q21-22;q26); and (iii) high platelet counts and dystrophic megakaryocytes. Thirty-four other patients with hematological malignancies, among which 11 had chromosomal rearrangements in the 3q24-q28 region did not exhibit such abnormalities. Of the 13 permanent hemopoietic cell lines tested, Evi-1 RNA expression was found in HEL and K-562 cell lines. Weak Evi-1 expression was also seen in fibroblasts and lung cells. This expression was affected neither in skin cells from a patient with a 3q27 constitutional translocation nor in a lung epithelioma cell line containing an excess of chromosome 3 long arm. Ectopic strong expression of Evi-1 in human leukemias could define an uncommon subclass of acute myelogenous leukemias with translocations involving the 3q25-28 chromosomal domain and abnormal megakaryopoiesis.

Adult↗