CALCRL, short for calcitonin receptor-like receptor, is a G-protein-coupled neuropeptide receptor. It is involved in multiple biological processes such as cell proliferation, apoptosis, and drug resistance. It is a key component of the receptor for neuropeptides like calcitonin gene-related peptide (CGRP) and adrenomedullin (ADM), participating in pathways like cyclic AMP (cAMP) signaling, which are crucial for various physiological functions [1,2,4,5,6].

In acute myeloid leukemia (AML), CALCRL knockdown in patient-derived xenograft models impairs leukemic growth, decreases the frequency of relapse-initiating drug-tolerant cells, and sensitizes cells to cytarabine [2]. In AML/ETO + AML patients, lower CALCRL expression is associated with longer median survival time, and its expression decreases after achieving complete remission following chemotherapy [3]. Also, in AML cell lines, overexpression of CALCRL confers resistance to daunorubicin, and interfering with its expression by knocking down XRCC5, a gene positively correlated with CALCRL, can upregulate drug sensitivity [7]. In glioma, knockdown of CALCRL in the U87 cell line significantly decreases cell proliferation and clonogenic ability while increasing the apoptosis rate, and its high expression in low-grade glioma (LGG) is related to prognosis [8].

In summary, CALCRL plays important roles in cell-related biological functions and drug-resistance-associated processes. Studies using knockdown or overexpression models in diseases like AML and glioma have revealed its significance in disease prognosis and drug resistance, providing potential therapeutic targets for these diseases.

References:

1. Wu, Min, Song, Guangping, Li, Jianing, Zhang, Yucheng, Li, Huiyan. 2024. Innervation of nociceptor neurons in the spleen promotes germinal center responses and humoral immunity. In Cell, 187, 2935-2951.e19. doi:10.1016/j.cell.2024.04.027. https://pubmed.ncbi.nlm.nih.gov/38772371/

2. Larrue, Clément, Guiraud, Nathan, Mouchel, Pierre-Luc, Récher, Christian, Sarry, Jean-Emmanuel. 2021. Adrenomedullin-CALCRL axis controls relapse-initiating drug tolerant acute myeloid leukemia cells. In Nature communications, 12, 422. doi:10.1038/s41467-020-20717-9. https://pubmed.ncbi.nlm.nih.gov/33462236/

3. Wang, Rongrong, Li, Miao, Bai, Yujia, Jiao, Yang, Qi, Xiaofei. 2022. CALCRL Gene is a Suitable Prognostic Factor in AML/ETO+ AML Patients. In Journal of oncology, 2022, 3024360. doi:10.1155/2022/3024360. https://pubmed.ncbi.nlm.nih.gov/35342399/

4. Zhao, Xibang, Wu, Guanfu, Zhang, Jing, Yu, Ziyi, Wang, Jiali. 2024. Activation of CGRP receptor-mediated signaling promotes tendon-bone healing. In Science advances, 10, eadg7380. doi:10.1126/sciadv.adg7380. https://pubmed.ncbi.nlm.nih.gov/38457499/

5. Gao, Xin, Zhang, Dachuan, Xu, Chunliang, Caron, Kathleen M, Frenette, Paul S. 2020. Nociceptive nerves regulate haematopoietic stem cell mobilization. In Nature, 589, 591-596. doi:10.1038/s41586-020-03057-y. https://pubmed.ncbi.nlm.nih.gov/33361809/

6. Hou, Yu, Sun, Linyu, LaFleur, Martin W, Sharpe, Arlene H, Kuchroo, Vijay K. 2024. Neuropeptide signalling orchestrates T cell differentiation. In Nature, 635, 444-452. doi:10.1038/s41586-024-08049-w. https://pubmed.ncbi.nlm.nih.gov/39415015/

7. Tang, Shanhao, Li, Shuangyue, Shi, Xiaowei, Wu, An, Ouyang, Guifang. 2023. CALCRL induces resistance to daunorubicin in acute myeloid leukemia cells through upregulation of XRCC5/TYK2/JAK1 pathway. In Anti-cancer drugs, 35, 163-176. doi:10.1097/CAD.0000000000001547. https://pubmed.ncbi.nlm.nih.gov/37948318/

8. Gu, Shengcai, Shu, Lei, Zhou, Lv, Gao, Peng, Cheng, Hongwei. . Interfering with CALCRL expression inhibits glioma proliferation, promotes apoptosis, and predicts prognosis in low-grade gliomas. In Annals of translational medicine, 10, 1277. doi:10.21037/atm-22-5154. https://pubmed.ncbi.nlm.nih.gov/36618798/