GAS6 expression identifies high-risk adult AML patients: potential implications for therapy View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-12-11

AUTHORS

S P Whitman, J Kohlschmidt, K Maharry, S Volinia, K Mrózek, D Nicolet, S Schwind, H Becker, K H Metzeler, J H Mendler, A-K Eisfeld, A J Carroll, B L Powell, T H Carter, M R Baer, J E Kolitz, I-K Park, R M Stone, M A Caligiuri, G Marcucci, C D Bloomfield

ABSTRACT

Emerging data demonstrate important roles for the TYRO3/AXL/MERTK receptor tyrosine kinase (TAM RTK) family in diverse cancers. We investigated the prognostic relevance of GAS6 expression, encoding the common TAM RTK ligand, in 270 adults (n=71 aged<60 years; n=199 aged ⩾60 years) with de novo cytogenetically normal acute myeloid leukemia (CN-AML). Patients expressing GAS6 (GAS6+), especially those aged ⩾60 years, more often failed to achieve a complete remission (CR). In all patients, GAS6+ patients had shorter disease-free (DFS) and overall (OS) survival than patients without GAS6 expression (GAS6−). After adjusting for other prognostic markers, GAS6+ predicted CR failure (P=0.02), shorter DFS (P=0.004) and OS (P=0.04). To gain further biological insights, we derived a GAS6-associated gene-expression signature (P<0.001) that in GAS6+ patients included overexpressed BAALC and MN1, known to confer adverse prognosis in CN-AML, and overexpressed CXCL12, encoding stromal cell-derived factor, and its receptor genes, chemokine (C-X-C motif) receptor 4 (CXCR4) and CXCR7. This study reports for the first time that GAS6 expression is an adverse prognostic marker in CN-AML. Although GAS6 decoy receptors are not yet available in the clinic for GAS6+ CN-AML therapy, potential alternative therapies targeting GAS6+-associated pathways, for example, CXCR4 antagonists, may be considered for GAS6+ patients to sensitize them to chemotherapy. More... »

PAGES

1252-1258

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/leu.2013.371

DOI

http://dx.doi.org/10.1038/leu.2013.371

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1019108664

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24326683


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