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. 2022 Mar 16:2022:3024360.
doi: 10.1155/2022/3024360. eCollection 2022.

CALCRL Gene is a Suitable Prognostic Factor in AML/ETO+ AML Patients

Affiliations

CALCRL Gene is a Suitable Prognostic Factor in AML/ETO+ AML Patients

Rongrong Wang et al. J Oncol. .

Abstract

Introduction: 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.

Methods: First, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used to determine any differences in CALCRL expression in AML patients with and without AML/ETO and the prognostic significance of CALCRL expression in AML patients was further evaluated. Next, we detected the CALCRL expression level in 67 AML/ETO+ AML patients and 16 patients with nonmalignant hematological diseases using qRT-PCR and identified its prognostic relevance.

Results: Individuals in the group expressing low levels of CALCRL had a longer median survival time. In AML/ETO+ AML patients, higher mRNA levels of CALCRL were observed before treatment, which decreased after the complete remission that followed multiple chemotherapy sessions. Clinical features indicated that more patients in the CALCRLhigh group also had c-kit mutations compared with patients in other groups. Overall survival (OS) was longer in patients with lower levels of CALCRL 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 CALCRLlow group after hematopoietic stem cell transplantation (HSCT).

Conclusions: This preliminary study indicates that CALCRL could serve as a suitable prognostic factor in AML/ETO+ AML patients.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(a) CALCRL gene expression and survival time and survival status in the TCGA dataset. (b) CALCRL expression in AML with AML/ETO (n = 16) or without AML/ETO (n = 309).
Figure 2
Figure 2
(a) Quantification of CALCRL mRNAs in the BMNC bone marrow samples from patients with AML/ETO+ AML (n = 67) or nonmalignant blood disease (n = 16). (b) Correlation between CALCRL expression and clinical phase. CALCRL mRNAs were detected in pretreated patients (n = 67) and remission phase patients (n = 62). cDNAs from all samples were subjected to real-time quantitative RT-PCR analysis with primers specific for CALCRL and ABL. The ratio of the abundance of CALCRL transcripts to that of ABL transcripts (CALCRL/ABL) was calculated for statistical analysis. (c) Correlation between CALCRL expression before treatment and remission rate after the first course of induction chemotherapy.
Figure 3
Figure 3
(a) Correlation between CALCRL expression and survival outcomes. (b) Correlation between CALCRL expressions combined with bone marrow blast cells and survival outcomes. (c) Correlation between CALCRL expressions combined with c-kit mutations and survival outcomes. (d) Overall survival (OS) rates in AML/ETO+ AML patients after HSCT with CALCRL expression levels high (green) (n = 25) or low (blue) (n = 27) the median value. Statistical analysis was based on survival analysis.

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