Wang Rongrong, Li Miao, Bai Yujia, Jiao Yang, Qi Xiaofei
Department of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China.
National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Suzhou, China.
J Oncol. 2022 Mar 16;2022:3024360. doi: 10.1155/2022/3024360. eCollection 2022.
The t(8 ; 21) translocation is the most common chromosomal abnormality in human acute myeloid leukemia (AML) subtype 2 (M2), which forms the AML/ETO fusion gene. However, AML/ETO alone does not necessarily cause leukemia. Other factors are thought to contribute to the disease. Calcitonin receptor-like (CALCRL), a G-protein-coupled neuropeptide receptor, is involved in various biological processes, such as colony formation and drug resistance.
First, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used to determine any differences in expression in AML patients with and without AML/ETO and the prognostic significance of expression in AML patients was further evaluated. Next, we detected the expression level in 67 AML/ETO AML patients and 16 patients with nonmalignant hematological diseases using qRT-PCR and identified its prognostic relevance.
Individuals in the group expressing low levels of had a longer median survival time. In AML/ETO AML patients, higher mRNA levels of were observed before treatment, which decreased after the complete remission that followed multiple chemotherapy sessions. Clinical features indicated that more patients in the CALCRL group also had c-kit mutations compared with patients in other groups. Overall survival (OS) was longer in patients with lower levels of expression, especially in patients with c-kit mutations or with more blast cells in bone marrow (BM). In addition, a longer OS was observed in the CALCRL group after hematopoietic stem cell transplantation (HSCT).
This preliminary study indicates that CALCRL could serve as a suitable prognostic factor in AML/ETO AML patients.
t(8;21)易位是人类急性髓系白血病(AML)亚型2(M2)中最常见的染色体异常,它形成了AML/ETO融合基因。然而,单独的AML/ETO不一定会导致白血病。其他因素被认为与该疾病有关。降钙素受体样(CALCRL)是一种G蛋白偶联神经肽受体,参与多种生物学过程,如集落形成和耐药性。
首先,利用癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)来确定有或无AML/ETO的AML患者中CALCRL表达的差异,并进一步评估CALCRL表达在AML患者中的预后意义。接下来,我们使用qRT-PCR检测了67例AML/ETO AML患者和16例非恶性血液病患者的CALCRL表达水平,并确定了其预后相关性。
CALCRL低表达组个体的中位生存时间更长。在AML/ETO AML患者中,治疗前观察到较高的CALCRL mRNA水平,在多次化疗后的完全缓解后该水平下降。临床特征表明,与其他组患者相比,CALCRL组中有更多患者也存在c-kit突变。CALCRL表达水平较低的患者总生存期(OS)更长,尤其是那些有c-kit突变或骨髓中原始细胞较多的患者。此外,造血干细胞移植(HSCT)后,CALCRL组的OS更长。
这项初步研究表明,CALCRL可作为AML/ETO AML患者合适的预后因素。