Overexpression of HER2/neu oncogene in human pancreatic carcinoma

Acute myelogenous leukaemia with c-myc amplification and double minute chromosomes.

https://repub.eur.nl/pub/59065/REPUB_59065_OA.pdf

Review of clinical, cytogenetic, and molecular aspects of Ph-negative CML.

The structure and the expression of 11 cellular oncogenes (protooncogenes) were analyzed in primary cells from 20 acute lymphocytic (ALL) and 31 acute myelogenous (AML) leukemia patients. Neoplastic cells, obtained prior to initiation of therapy, were purified and classified, on the basis of both surface antigen pattern and morphology, into pre-B, B, and T ALL and M1-M5 AML. RNA was extracted and analyzed for expression of cellular oncogenes coding for nuclear proteins (c-myc, c-myb, c-fos), the beta-chain of platelet-derived growth factor (c-sis), growth factor receptors or related proteins (c-src, c-abl, c-fes, c-erbB), or putative intermediate transducers of mitogenic signals (c-Ha-ras, c-Ki-ras, c-N-ras). Quantitative analysis of total RNA was carried out by dot blot hybridization to specific cDNA or genomic probes. Number and size of transcripts were evaluated by blot hybridization of electrophoretically fractionated poly(A)+ RNA. Expression of c-myc and c-myb was detected in all leukemic cells at variable levels and was characterized by well-defined patterns within ALL subtypes. Conversely, significant levels of c-fos transcripts were detected only in myelomonocytic (M4) and monocytic (M5) leukemias. Among the "src-family," c-fes was expressed more in AML than ALL, and c-abl was expressed at variable but not elevated levels in all leukemia types. c-Ha-ras was uniformly expressed at low levels, as in non-neoplastic cells. c-Ki-ras transcription was detected only in T ALL; N-ras expression was barely demonstrable. The structure of these protooncogenes was not grossly modified, as evaluated by Southern analysis, except for c-myc rearrangement in B ALL. These studies indicate that cellular oncogene expression in specific subtypes of leukemic cells may relate to either the proliferative activity (c-myc, c-myb) or the differentiation state (c-fos) of the cells, or possibly to expression of receptors for putative hemopoiesis-related growth factors (c-fes, c-abl). Our data provide a basis for in-depth analysis of protooncogene expression in normal and neoplastic hemopoiesis.

Expression of cellular oncogenes in primary cells from human acute leukemias

In this study, a monoclonal antibody (mAb) termed SN6 was generated by immunizing a mouse with a non-T-cell leukemia antigen preparation isolated from cell membranes of leukemia cells derived from a patient (FJ) with non-T/non-B-cell-type acute lymphoblastic leukemia (ALL). SN6 was tested against a variety of cultured and uncultured human cell specimens by using a sensitive cellular radioimmunoassay. Among the 26 cultured malignant and nonmalignant cell lines tested, SN6 reacted with all of the 6 leukemic non-T/non-B (including pre-B)-cell lines tested--i.e., KM-3, NALM-16, REH, NALL-1, NALM-1, and NALM-6. Of these cell lines, 5 were derived from individual patients with ALL; the remaining 1 was from a patient with chronic myelocytic leukemia in blast crisis. In addition, SN6 reacted with 3 of 3 leukemic myelo-monocytic cell lines tested--i.e., ML-2, HL-60, and U937. SN6 did not react with any other cell lines. A consistent result was obtained with 42 fresh (uncultured) cell specimens derived from individual patients with several different types of leukemias. SN6 reacted with 11 of 16 non-T/non-B (including pre-B)-cell ALL specimens. In addition, it reacted with various myelo-monocytic leukemia cell specimens to various degrees. SN6 did not show a significant reaction with normal peripheral blood cells tested, which included B cells, T cells, granulocytes, monocytes, and erythrocytes. However, it reacted with a small population (approximately 1% as determined by immunofluorescence staining) of normal bone marrow cells. The approximate molecular mass of the glycoprotein antigen defined by SN6 was determined to be 160,000 by radioimmunoprecipitation followed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. Only one component of 80,000 daltons was formed upon reduction of the 160,000 molecular mass antigen. Therefore, this antigen is apparently a homodimer of a 80,000-dalton subunit. This conclusion was further corroborated by two-dimensional gel analysis, which showed a single well-defined spot for the reduced antigen. We designate this distinct human leukemia-associated cell surface antigen "GP160."

https://www.pnas.org/content/pnas/83/20/7898.full.pdf

Distinct human leukemia-associated cell surface glycoprotein GP160 defined by monoclonal antibody SN6.

Oncogene expression in human leukemia

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Oncogene expression in human leukemia