AML1-ETO fusion protein up-regulates TRKA mRNA expression in human CD34+ cells, allowing nerve growth factor-induced expansion Journal Article
| Authors: | Mulloy, J. C.; Jankovic, V.; Wunderlich, M.; Delwel, R.; Cammenga, J.; Krejci, O.; Zhao, H.; Valk, P. J. M.; Löwenberg, B.; Nimer, S. D. |
| Article Title: | AML1-ETO fusion protein up-regulates TRKA mRNA expression in human CD34+ cells, allowing nerve growth factor-induced expansion |
| Abstract: | The AML1-ETO fusion protein, generated by the t(8;21) in acute myeloid leukemia (AML), exerts dominant-negative functions and a variety of gains of function, including a positive effect on the growth of primary human CD34 + hematopoietic stem/progenitor cells. We now show that AML1-ETO expression up-regulates the level of TRKA mRNA and protein in these cells and that AML1-ETO-expressing CD34+ hematopoietic cells grown in the presence of five early-acting hematopoietic cytokines further proliferate in response to nerve growth factor (NGF). These cells also show a unique response to NGF and IL-3; namely, they expand in liquid culture. To determine the biological relevance of our findings, we analyzed 262 primary AML patient samples using real-time RT-PCR and found that t(8;21)-positive AML samples express significantly higher levels of TRKA mRNA than other subtypes of AML. NGF, which is normally expressed by bone marrow stromal cells, could provide important proliferative or survival signals to AML1-ETO-expressing leukemic or preleukemic cells, and the NGF/TRKA signaling pathway may be a suitable target for therapeutic approaches to AML. © 2005 by The National Academy of Sciences of the USA. |
| Keywords: | controlled study; protein expression; leukemia; unclassified drug; oncoprotein; acute granulocytic leukemia; human cell; cell proliferation; cell survival; cell division; bone marrow; transcription factors; gene expression regulation; oncogene; cytokine; hybrid protein; messenger rna; leukemia cell; oncogene proteins, fusion; hematopoietic stem cells; translocation, genetic; real time polymerase chain reaction; upregulation; hematopoietic stem cell; up-regulation; antigens, cd34; cd34 selection; cell activity; core binding factor alpha 2 subunit; transcription factor runx1; cytokine receptor; protein tyrosine kinase a; protein aml1 eto; interleukin 3; nerve growth factor; t(8; 21); leukemia, myelocytic, acute; receptor, trka; cellular context; target gene; liquid culture |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 102 |
| Issue: | 11 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2005-03-15 |
| Start Page: | 4016 |
| End Page: | 4021 |
| Language: | English |
| DOI: | 10.1073/pnas.0404701102 |
| PUBMED: | 15731354 |
| PROVIDER: | scopus |
| PMCID: | PMC554792 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 42" - "Export Date: 24 October 2012" - "CODEN: PNASA" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work