Focal adhesion kinase as a potential target inAML & MDS

Bing Z. Carter, Po Yee Mak, Xiangmeng Wang, Hui Yang, Guillermo Garcia-Manero, Duncan H. Mak, Hong Mu, Vivian R. Ruvolo, Yihua Qiu, Kevin Coombes, Nianxiang Zhang, Brittany Ragon, David Tweaver, Jonathan A. Pachter, Steven Kornblau, Michael Andreeff

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


Although overexpression/activation of focal adhesion kinase (FAK) is widely known in solid tumors to control cell growth, survival, invasion, metastasis, gene expression, and stem cell selfrenewal, its expression and function in myeloid leukemia are not well investigated. Using reverse-phase protein arrays in large cohorts of newly diagnosed acute myeloid leukemia (AML) and myeloid dysplastic syndrome (MDS) samples, we found that high FAK expression was associated with unfavorable cytogenetics (P= 2 × 10-4) and relapse (P = 0.02) in AML. FAK expression was significantly lower in patients with FLT3-ITD (P=0.0024) or RAS (P = 0.05) mutations and strongly correlated with p-SRC and integrinb3 levels. FAK protein levels were significantly higher in CD34 (P = 5.42 × 10-20) and CD34+CD38- MDS (P = 7.62 × 10-9) cells compared with normal CD34 cells. MDS patients with higher FAK in CD34 cells tended to have better overall survival (P = 0.05). FAK expression was significantly higher in MDS patients who later transformed to compared with those who did not transform to AML and in AML patients who transformed fromMDScompared with those with de novo AML. Coculture with mesenchymal stromal cells (MSC) increased FAK expression in AML cells. Inhibition of FAK decreased MSC-mediated adhesion/ migration and viability of AML cells and prolonged survival in an AML xenograft murine model. Our results suggest that FAK regulates leukemia-stromal interactions and supports leukemia cell survival; hence, FAK is a potential therapeutic target in myeloid leukemia.

Original languageEnglish (US)
Pages (from-to)1133-1144
Number of pages12
JournalMolecular cancer therapeutics
Issue number6
StatePublished - Jun 2017
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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