Anti-CD44 Antibodies Inhibit Both mTORC1 and mTORC2 Activities in Acute Myeloid Leukemia.

Research output: Contribution to journalArticlepeer-review


Abstract Abstract 2620 The role of aberrant signaling pathways such as the PI3K/Akt and the mammalian target of rapamycin (mTor) in the uncontrolled growth and survival in cancer including acute myeloid leukemia (AML) is now clearly demonstrated; and inhibitors of mTor such as Rapamycin are currently being used in clinical trials for their potent anti-neoplastic effects. While leaving normal hematopoiesis unaffected, anti-CD44 monoclonal antibodies (mAbs) have been shown to reverse the blockage of differentiation responsible for the leukemic phenotype, inhibit proliferation of the leukemic clones, and in some types of leukemia, induce the apoptosis of leukemic blasts. However, the molecular mechanisms underlying these effects are yet to be resolved. Here, we show that anti-CD44 mAb-induced differentiation of the HL60 cell line (AML type 2), is accompanied by a marked decrease in the phosphorylation of mTor with no affect on the total expression of mTor. This decrease was strongly correlated with an inhibition of the PI3K/Akt pathway as shown by the decrease of Akt phosphorylation on Thr308. Moreover, we observed that anti-CD44 mAbs induce a decrease of phosphorylation of p70S6k (on Thr 389) as well a decrease in the phosphorylation of Akt on Ser 473, which directly reflect the activity of mTORC1 and mTORC2 respectively. This result strongly suggests that CD44 triggering inhibits the activity of both mTORC1 and mTORC2 complexes. Previous studies have shown that the activity of mTORC1 is constitutively active in most leukemic patients, while it has been suggested that the inhibition of mTORC2 activity could have an anti-leukemic effect. Our finding unveils a new role for anti-CD44 mAbs as potent mTor inhibitors, heretofore, adding a key argument to the promise of CD44 as a strong therapeutic target in AML. Disclosures: No relevant conflicts of interest to declare.
Original languageEnglish (US)
Pages (from-to)2620-2620
Number of pages1
Issue number21
StatePublished - Nov 16 2012

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Immunology
  • Hematology


Dive into the research topics of 'Anti-CD44 Antibodies Inhibit Both mTORC1 and mTORC2 Activities in Acute Myeloid Leukemia.'. Together they form a unique fingerprint.

Cite this