TY - JOUR
T1 - Loss of TRIM62 expression is an independent adverse prognostic factor in acute myeloid leukemia
AU - Quintás-Cardama, Alfonso
AU - Zhang, Nianxiang
AU - Qiu, Yi Hua
AU - Post, Sean
AU - Creighton, Chad J.
AU - Cortes, Jorge
AU - Coombes, Kevin R.
AU - Kornblau, Steven M.
N1 - Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/2/1
Y1 - 2015/2/1
N2 - Background Tripartite motif (TRIM)-62 is a putative tumor suppressor gene whose role in leukemia is unknown. Materials and Methods We evaluated the effect of TRIM62 protein expression in patients with acute myeloid leukemia (AML). We used reverse-phase protein array methodology to determine TRIM62 levels in leukemia-enriched protein samples from 511 patients newly diagnosed with AML. Results TRIM62 levels in AML cells were significantly lower than in normal CD34-positive cells, suggesting that TRIM62 loss might be involved in leukemogenesis, but was not associated with specific karyotypic abnormalities or Nucleophosmin (NPM1), Fms-like Tyrosine Kinase-3 (FLT3), or rat sarcoma viral oncogene (RAS) mutational status. Low TRIM62 levels were associated with shorter complete remission duration and significantly shorter event-free and overall survival rates, particularly among patients with intermediate-risk cytogenetics. In that AML subgroup, age and TRIM62 levels were the most powerful independent prognostic factors for survival. TRIM62 protein levels further refined the risk associated with NPM1 and FLT3 mutational status. TRIM62 loss was associated with altered expression of proteins involved in leukemia stem cell homeostasis (β-catenin and Notch), cell motility, and adhesion (integrin-β3, ras-related C3 botulinum toxin substrate [RAC], and fibronectin), hypoxia (Hypoxia-inducible factor 1-alpha [HIF1α], egl-9 family hypoxia-inducible factor 1 [Egln1], and glucose-regulated protein, 78kDa [GRP78]), and apoptosis (B-cell lymphoma-extra large (BclXL) and caspase 9). Conclusion Low TRIM62 levels, consistent with a tumor suppressor role, represent an independent adverse prognostic factor in AML.
AB - Background Tripartite motif (TRIM)-62 is a putative tumor suppressor gene whose role in leukemia is unknown. Materials and Methods We evaluated the effect of TRIM62 protein expression in patients with acute myeloid leukemia (AML). We used reverse-phase protein array methodology to determine TRIM62 levels in leukemia-enriched protein samples from 511 patients newly diagnosed with AML. Results TRIM62 levels in AML cells were significantly lower than in normal CD34-positive cells, suggesting that TRIM62 loss might be involved in leukemogenesis, but was not associated with specific karyotypic abnormalities or Nucleophosmin (NPM1), Fms-like Tyrosine Kinase-3 (FLT3), or rat sarcoma viral oncogene (RAS) mutational status. Low TRIM62 levels were associated with shorter complete remission duration and significantly shorter event-free and overall survival rates, particularly among patients with intermediate-risk cytogenetics. In that AML subgroup, age and TRIM62 levels were the most powerful independent prognostic factors for survival. TRIM62 protein levels further refined the risk associated with NPM1 and FLT3 mutational status. TRIM62 loss was associated with altered expression of proteins involved in leukemia stem cell homeostasis (β-catenin and Notch), cell motility, and adhesion (integrin-β3, ras-related C3 botulinum toxin substrate [RAC], and fibronectin), hypoxia (Hypoxia-inducible factor 1-alpha [HIF1α], egl-9 family hypoxia-inducible factor 1 [Egln1], and glucose-regulated protein, 78kDa [GRP78]), and apoptosis (B-cell lymphoma-extra large (BclXL) and caspase 9). Conclusion Low TRIM62 levels, consistent with a tumor suppressor role, represent an independent adverse prognostic factor in AML.
KW - AML
KW - Proteomics
KW - RPPA
KW - Reverse phase protein array
KW - TRIM62
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U2 - 10.1016/j.clml.2014.07.011
DO - 10.1016/j.clml.2014.07.011
M3 - Article
C2 - 25248926
AN - SCOPUS:84921684372
SN - 2152-2650
VL - 15
SP - 115-127.e15
JO - Clinical Lymphoma, Myeloma and Leukemia
JF - Clinical Lymphoma, Myeloma and Leukemia
IS - 2
ER -