CAMKs support development of acute myeloid leukemia

Journal of Hematology & Oncology
Xunlei KangCheng Cheng Zhang

Abstract

We recently identified the human leukocyte immunoglobulin-like receptor B2 (LILRB2) and its mouse ortholog-paired Ig-like receptor (PirB) as receptors for several angiopoietin-like proteins (Angptls). We also demonstrated that PirB is important for the development of acute myeloid leukemia (AML), but exactly how an inhibitory receptor such as PirB can support cancer development is intriguing. Here, we showed that the activation of Ca (2+)/calmodulin-dependent protein kinases (CAMKs) is coupled with PirB signaling in AML cells. High expression of CAMKs is associated with a poor overall survival probability in patients with AML. Knockdown of CAMKI or CAMKIV decreased human acute leukemia development in vitro and in vivo. Mouse AML cells that are defective in PirB signaling had decreased activation of CAMKs, and the forced expression of CAMK partially rescued the PirB-defective phenotype in the MLL-AF9 AML mouse model. The inhibition of CAMK kinase activity or deletion of CAMKIV significantly slowed AML development and decreased the AML stem cell activity. We also found that CAMKIV acts through the phosphorylation of one of its well-known target (CREB) in AML cells. CAMKs are essential for the growth of human and mouse AML. The in...Continue Reading

References

Apr 16, 1998·Proceedings of the National Academy of Sciences of the United States of America·M BléryE Vivier
Jul 16, 2005·The Journal of Biological Chemistry·Christine M KitsosAnthony R Means
Jul 25, 2006·Nature·Andrei V KrivtsovScott A Armstrong
Aug 19, 2006·Science·Josh SykenCarla J Shatz
Nov 3, 2007·Blood·Jerry C ChengKathleen M Sakamoto
Mar 20, 2009·Nature Immunology·Lionel B Ivashkiv
Apr 10, 2010·Nature Biotechnology·Margus LukkAlvis Brazma
Oct 27, 2010·Journal of Biomedicine & Biotechnology·Toshiyuki TakaiShota Endo
Nov 7, 2013·Journal of Hematology & Oncology·Xiaoli ChenCheng Cheng Zhang
Dec 18, 2013·Science·Tim WangEric S Lander
Jun 6, 2014·Blood·Mi DengCheng Cheng Zhang
Feb 5, 2015·Journal of Hematology & Oncology·Jingjing XieCheng Cheng Zhang
Apr 29, 2015·Nature Cell Biology·Xunlei KangCheng Cheng Zhang

❮ Previous
Next ❯

Citations

Jan 29, 2019·Journal of Biochemistry·Tsuyoshi Kadomatsu, Yuichi Oike
Jan 17, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Sean N O'ByrneDavid H Drewry
Dec 10, 2020·Experimental Hematology & Oncology·Hongying ZhangHui Hua
May 1, 2021·Antibody Therapeutics·Mi DengCheng Cheng Zhang

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
Transfection
flow cytometry
xenograft
electrophoresis
flow
pull-down
immunoprecipitation
co-immunoprecipitation

Software Mentioned

Calc

Related Concepts

Related Feeds

AML: Role of LSD1 by CRISPR (Keystone)

Find the latest rersearrch on the ability of CRISPR-Cas9 mutagenesis to profile the interactions between lysine-specific histone demethylase 1 (LSD1) and chemical inhibitors in the context of acute myeloid leukemia (AML) here.

Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous disease with approximately 20,000 cases per year in the United States. AML also accounts for 15-20% of all childhood acute leukemias, while it is responsible for more than half of the leukemic deaths in these patients. Here is the latest research on this disease.