β-Catenin and AKT are promising targets for combination therapy in acute myeloid leukemia.

نویسندگان

  • L Wang
  • L-S You
  • W-M Ni
  • Q-L Ma
  • Y Tong
  • L-P Mao
  • J-J Qian
  • J Jin
چکیده

In this study, we confirmed that combining HHT with ACR can result in synergistic cytotoxicity to AML cells in vitro and in vivo. Combining HHT and ACR simultaneously inhibited PI3K/AKT and WNT/β-catenin signaling in AML cells. Significant increases in growth inhibition and apoptosis were induced by an AKT inhibitor when the WNT3A gene of THP-1 cells was silenced. HHT+ACR could synergistically induce the apoptosis of CD34(+)/CD38(-) primary AML cells. These results highlight β-catenin and AKT are promising targets for combination therapy for AML.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

The role of sirtuin 2 activation by nicotinamide phosphoribosyltransferase in the aberrant proliferation and survival of myeloid leukemia cells.

BACKGROUND Inhibitors of nicotinamide phosphoribosyltransferase have recently been validated as therapeutic targets in leukemia, but the mechanism of leukemogenic transformation downstream of this enzyme is unclear. DESIGN AND METHODS Here, we evaluated whether nicotinamide phosphoribosyltransferase's effects on aberrant proliferation and survival of myeloid leukemic cells are dependent on si...

متن کامل

Anti-Apoptotic Effects of Osteopontin via the Up-Regulation of AKT/mTOR/β-Catenin Loop in Acute Myeloid Leukemia Cells

Background: The conventional chemotherapeutic regimens which applied for treatment of acute myeloid leukemia (AML) mostly target tumor bulk but not leukemic stem cells (LSCs). Aberrant expression or activation of mediators such as osteopontin (OPN) or PI3K/PTEN/Akt/mTOR pathway plays a key role in making prone to develop leukemia. Preventing or treating cancer by curcumin (CUR) has been suggest...

متن کامل

Effective Dendritic Cell-based Immunotherapeutic Vaccines for Acute Myeloid Leukemia (AML)

Acute myeloid leukemia (AML) is a type of poor prognosis hematological malignancies characterized by heterogeneous clonal expansion of myeloid progenitors. Leukemic stem cells are thought to form the majority of a cell population in minimal residual diseases (MRDs) which are resistant to current chemotherapeutic regimens and mediate disease relapse. Current therapeutic vaccine strategies have d...

متن کامل

Treatment of a Child with Refractory Acute Myeloid Leukemia with Humanized Anti-CD33 Monoclonal Antibody: A Case Report and Review of Drug Development

Background: The induction chemotherapy regimen for acute myeloid leukemia has evolved as once induction is completed patients progress through the consolidation phase and achieve remission in 76% of cases. For patients with relapsed or refractory disease, alternative chemotherapy agents are available. Monoclonal antibody therapy with biological agents, such as the immunotoxin gemtuzumab ozog...

متن کامل

JAM3 maintains leukemia-initiating cell self-renewal through LRP5/AKT/β-catenin/CCND1 signaling.

Leukemia-initiating cells (LICs) are responsible for the initiation, development, and relapse of leukemia. The identification of novel therapeutic LIC targets is critical to curing leukemia. In this report, we reveal that junctional adhesion molecule 3 (JAM3) is highly enriched in both mouse and human LICs. Leukemogenesis is almost completely abrogated upon Jam3 deletion during serial transplan...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Leukemia research

دوره 37 10  شماره 

صفحات  -

تاریخ انتشار 2013