PuSH - Publication Server of Helmholtz Zentrum München: The neuropeptide receptor calcitonin receptor-like (CALCRL) is a potential therapeutic target in acute myeloid leukemia.

Navigation

Home

Deutsch

Research

Advanced Search

Browse by ...

... Journal

... Publication Type

... Research Data

... Publication Year

Publication overview

Support & Contact

Contact persons

Help

Data protection

Angenendt, L.* ; Bormann, E.* ; Pabst, C.* ; Alla, V.* ; Görlich, D.* ; Braun, L.* ; Dohlich, K.* ; Schwöppe, C.* ; Bohlander, S.K.* ; Arteaga, M.F.* ; Wethmar, K.* ; Hartmann, W.* ; Angenendt, A.* ; Kessler, T.* ; Mesters, R.M.* ; Stelljes, M.* ; Rothenberg-Thurley, M.* ; Spiekermann, K.* ; Hébert, J.* ; Sauvageau, G.* ; Valk, P.J.M.* ; Löwenberg, B.* ; Serve, H.* ; Müller-Tidow, C.* ; Lenz, G.* ; Wörmann, B.J.* ; Sauerland, M.C.* ; Hiddemann, W.* ; Berdel, W.E.* ; Krug, U.* ; Metzeler, K.H.* ; Mikesch, J.H.* ; Herold, T. ; Schliemann, C.

The neuropeptide receptor calcitonin receptor-like (CALCRL) is a potential therapeutic target in acute myeloid leukemia.

Leukemia 33, 2830-2841 (2019)

Publ. Version/Full Text

Postprint

DOI

PMC

	Open Access Green

Abstract
Metrics
Extra information

Calcitonin receptor-like (CALCRL) is a G-protein-coupled neuropeptide receptor involved in the regulation of blood pressure, angiogenesis, cell proliferation, and apoptosis, and is currently emerging as a novel target for the treatment of migraine. This study characterizes the role of CALCRL in acute myeloid leukemia (AML). We analyzed CALCRL expression in collectively more than 1500 well-characterized AML patients from five international cohorts (AMLCG, HOVON, TCGA, Leucegene, and UKM) and evaluated associations with survival. In the AMLCG analytic cohort, increasing transcript levels of CALCRL were associated with decreasing complete remission rates (71.5%, 53.7%, 49.6% for low, intermediate, high CALCRL expression), 5-year overall (43.1%, 26.2%, 7.1%), and event-free survival (29.9%, 15.8%, 4.7%) (all P < 0.001). CALCRL levels remained associated with all endpoints on multivariable regression analyses. The prognostic impact was confirmed in all validation sets. Genes highly expressed in CALCRLhigh AML were significantly enriched in leukemic stem cell signatures and CALCRL levels were positively linked to the engraftment capacity of primary patient samples in immunocompromised mice. CRISPR- Cas9-mediated knockout of CALCRL significantly impaired colony formation in human myeloid leukemia cell lines. Overall, our study demonstrates that CALCRL predicts outcome beyond existing risk factors and is a potential therapeutic target in AML.

Altmetric

Additional Metrics?

[➜Log in]

Edit extra informations Login

Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Gene-related Peptide; Bone-marrow; Baalc Expression; Tumor Xenograft; In-vitro; Adrenomedullin; Growth; Angiogenesis; Cancer; Stimulation

ISSN (print) / ISBN 0887-6924

e-ISSN 1476-5551

Journal Leukemia

Quellenangaben Volume: 33, Issue: 12, Pages: 2830-2841

Publisher Nature Publishing Group

Publishing Place Macmillan Building, 4 Crinan St, London N1 9xw, England

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Research Unit Apoptosis in Hematopoietic Stem Cells (AHS)