Format

Send to

Choose Destination
J Hematol Oncol. 2018 Feb 27;11(1):30. doi: 10.1186/s13045-018-0574-8.

CAMKs support development of acute myeloid leukemia.

Author information

1
Departments of Physiology and Developmental Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, 75390, USA. kangxu@health.missouri.edu.
2
Center for Precision Medicine, Department of Medicine, University of Missouri, 1 Hospital Drive, Columbia, MO, 65212, USA. kangxu@health.missouri.edu.
3
Departments of Physiology and Developmental Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, 75390, USA.
4
School of Life Science and Medicine, Dalian University of Technology, Liaoning, 124221, China.
5
Center for Precision Medicine, Department of Medicine, University of Missouri, 1 Hospital Drive, Columbia, MO, 65212, USA.
6
Department of Hematology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
7
Department of Electrical and Computer Engineering, Missouri University of Science and Technology, Rolla, MO, 65409, USA.
8
Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, 94143, USA.
9
Department of Systems Biology, Beckman Research Institute, Monrovia, CA, 91016, USA.
10
Department of Pathology, University of California San Diego, La Jolla, CA, 92093, USA.
11
Departments of Physiology and Developmental Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, 75390, USA. Alec.Zhang@UTSouthwestern.edu.

Abstract

BACKGROUND:

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.

RESULTS:

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.

CONCLUSION:

CAMKs are essential for the growth of human and mouse AML. The inhibition of CAMK signaling may become an effective strategy for treating leukemia.

KEYWORDS:

Acute myeloid leukemia; CAMK; CREB; LILRB2; Leukemic stem cell; PirB

PMID:
29482582
PMCID:
PMC5828341
DOI:
10.1186/s13045-018-0574-8
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center