GAS6 expression identifies high-risk adult AML patients: potential implications for therapy
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...
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Published in | Leukemia Vol. 28; no. 6; pp. 1252 - 1258 |
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Main Authors | , , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
01.06.2014
Nature Publishing Group |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0887-6924 1476-5551 |
DOI: | 10.1038/leu.2013.371 |