Expression of Cellular Oncogenes in Primary Cells from Human Acute Leukemias

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 83; no. 12; pp. 4394 - 4398
• Main Authors: Mavilio, F., Sposi, N. M., Petrini, M., Bottero, L., Marinucci, M., De Rossi, G., Amadori, S., Mandelli, F., Peschle, C.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.06.1986; National Acad Sciences
• Subjects: Biological and medical sciences; Cell growth; Cell lines; Complementary DNA; DNA, Neoplasm - genetics; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation; Genes; Genomics; Humans; Leukemia; Leukemia, Lymphoid - genetics; Leukemia, Myeloid, Acute - genetics; Molecular and cellular biology; Molecular genetics; Myeloid leukemia; Oncogenes; Proto-Oncogene Proteins - genetics; Proto-Oncogenes; RNA; RNA, Messenger - genetics; RNA, Neoplasm - genetics; T lymphocytes; Transcription, Genetic; Human; Regulation(control); Gene expression; C-Onc gene; Leukemia; Tumor cell
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.83.12.4394

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 β -chain of plateletderived 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 protoncogene expression in normal and neoplastic hemopoiesis.