Application of small peptide PEARL in diagnosis and targeted therapy of acute myeloid leukemia

Abstract

The application belongs to the technical field of biological medicine, and particularly relates to application of a small peptide PEARL in diagnosis and targeted treatment of acute myeloid leukemia. The application detects samples of leukemia patients and leukemia cell lines, and finds that the small peptide PEARL is significantly lowly expressed in patients with acute myeloid leukemia. Meanwhile, it is found through research that PROSER2-AS1 does not play a role by itself, but plays a function through the coded small peptide PEARL. Further through a mouse leukemia model experiment, it is found that overexpression of the small peptide PEARL can significantly inhibit survival of acute myeloid leukemia cells, and significantly prolong the survival cycle of model mice. Finally, through mechanism research, it is found that overexpression of PEARL significantly increases endoplasmic reticulum stress of acute myeloid leukemia cells, activates UPR response, and thus affects functions of the acute myeloid leukemia cells. Therefore, the application can provide a new precise judgment or treatment strategy for diagnosis or targeted treatment of acute myeloid leukemia.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of biological medicine, and particularly relates to application of a small peptide PEARL in diagnosis and targeted treatment of acute myeloid leukemia. BACKGROUND

[0002] Acute myeloid leukemia (AML) is a malignant tumor characterized by differentiation block and malignant proliferation of hematopoietic stem / progenitor cells, accounting for about 70% of all acute leukemias. At present, due to unclear pathogenesis of acute myeloid leukemia and frequent occurrence of drug-resistant clones, the treatment of acute myeloid leukemia is difficult, and the prognosis and survival rate are not ideal.

[0003] Therefore, the research on the same or different targets in different types of acute myeloid leukemia will play an important role in the treatment of leukemia. Studies have shown that unfolded protein response (UPR) is one of the main adaptive cellular stress responses leading to the development of drug and chemotherapy resistance in AML leukemia. Therefore, targeting UPR may be a new AML treatment strategy.

[0004] With the development and maturity of technologies such as transcriptomics and proteomics, more and more studies have shown that some RNA regions that are traditionally considered not to encode proteins, including long non-coding RNAs, actually also have open reading frames (ORF) with usually less than 300 nucleotides (nt), which are called small open reading frames (sORF), and small peptides are translated from them. Transcriptome sequencing results show that a large number of non-coding RNAs (such as lncRNA) encoding small peptides are abnormally expressed in cancer. Current studies show that many small peptides are dysregulated in cancer and regulate the growth, invasion and metastasis of cancer cells. In recent years, with the development of ribosome profiling technology, it has also been gradually revealed that long non-coding RNAs that encode small peptides play an important role in life activities, diseases and cancer. However, the current research on small peptides is still in its infancy, and the functions of many small peptides have not been explored, and there is a lack of relevant research in leukemia. SUMMARY

[0005] In order to overcome the above deficiencies of the prior art, the present application finds and identifies a small peptide PEARL (A Peptide located in Endoplasmic Reticulum derived from a LncRNA PROSER2-AS1) which is lowly expressed in acute myeloid leukemia, and discloses that the small peptide is an important regulatory molecule in leukemia, which enriches the research on small peptides on the one hand, and provides a theoretical basis for comprehensively understanding the occurrence and development of leukemia, and provides a new target for the drug research and development of acute leukemia, and can also provide a positive reference for the mechanism research and potential therapeutic target of small peptides in other leukemia and cancers.

[0006] In order to achieve the above-mentioned purpose, the technical scheme adopted by the present application is:

[0007] The first aspect of the present application provides an application of a reagent for detecting the expression level of a small peptide PEARL encoded by lncRNA PROSER2-AS1 in the preparation of an acute myeloid leukemia diagnosis product, wherein the nucleic acid sequence of the lncRNA PROSER2-AS1 is shown as SEQ ID NO: 1, and the amino acid sequence of the small peptide PEARL is shown as SEQ ID NO: 2.

[0008] The present application finds and identifies a long non-coding RNA encoded small peptide PEARL gene which is lowly expressed in acute myeloid leukemia and relatively highly expressed under normal physiological conditions and in other types of cancers, and the gene is named as PROSER2-AS1 (ENSG00000225778). Further research finds that the expression level of PROSER2-AS1 / PEARL is significantly lowly expressed in patients with acute myeloid leukemia, which indicates that PROSER2-AS1 / PEARL has a potential clinical role as a classifier of acute myeloid leukemia.

[0009] Preferably, the reagent for detecting the expression level of the small peptide PEARL is a primer for detecting the expression amount of the small peptide PEARL, and the sequences are shown as SEQ ID NO: 3-4.

[0010] Preferably, the diagnosis product comprises a diagnosis chip or a kit.

[0011] The second aspect of the present application provides an application of a reagent for overexpressing a small peptide PEARL encoded by lncRNA PROSER2-AS1 in any one of the following 1)-4):

[0012] 1) preparing a product for treating acute myeloid leukemia;

[0013] 2) preparing a product for inhibiting the occurrence and development of acute myeloid leukemia;

[0014] 3) preparing a product for inhibiting the growth of acute myeloid leukemia cells;

[0015] 4) preparing a product for promoting the differentiation of acute myeloid leukemia cells.

[0016] The present application has been proved by research that, after overexpressing PROSER2-AS1 / PEARL by using a CMV-HA tag vector, the gene plays a role in a small peptide PEARL by translation instead of a lncRNA PROSER2-AS1, the small peptide can significantly inhibit the proliferation of acute myeloid leukemia cells and induce differentiation. Moreover, the NOD-SCID mouse model experiment shows that the acute myeloid leukemia cells overexpressing PEARL have the effect of inhibiting tumor growth.

[0017] Preferably, the inhibition of the occurrence and development of acute myeloid leukemia is to inhibit the translation level of acute myeloid leukemia cells.

[0018] More preferably, the inhibition of the translation level of acute myeloid leukemia cells significantly increases the endoplasmic reticulum stress of acute myeloid leukemia cells by interacting with the UPR response effector PERK, and activates the UPR response.

[0019] The present application further proves by related molecular biology experiments that PEARL regulates the UPR response by binding to PERK, directly affects the endoplasmic reticulum stress of cells, specifically by increasing the endoplasmic reticulum stress of acute myeloid leukemia cells, activating the UPR response, thereby inducing cell death and improving the survival period of the disease. It is illustrated that the present application can regulate the expression level of PROSER2-AS1 / PEARL by genetic engineering means, thereby increasing the endoplasmic reticulum stress of cells and inducing the UPR response, which has important value for the precise treatment of acute myeloid leukemia. At the same time, the present application also proves that PROSER2-AS1 / PEARL has potential clinical practical value in the classification of acute myeloid leukemia.

[0020] Preferably, the reagent for overexpressing the small peptide PEARL encoded by the lncRNA PROSER2-AS1 includes pCDH-CMV-MCS-EF1-Puro.

[0021] Preferably, the acute myeloid leukemia cells include MOLM-13 and HL60.

[0022] Preferably, the product is a drug.

[0023] The third aspect of the present application provides a therapeutic drug for acute myeloid leukemia, the drug comprising a reagent overexpressing a small peptide PEARL coded based on lncRNA PROSER2-AS1, the nucleic acid sequence of the lncRNA PROSER2-AS1 being shown as SEQ ID NO: 1, and the amino acid sequence of the small peptide PEARL being shown as SEQ ID NO: 2.

[0024] Preferably, the drug further comprises a pharmaceutically acceptable excipient.

[0025] More preferably, the excipient is a functional pharmaceutical excipient available in the pharmaceutical field, including but not limited to a surfactant, a suspending agent, an emulsifying agent, and some novel pharmaceutical polymer materials such as cyclodextrin, chitosan, polylactic acid (PLA), polylactic acid-glycolic acid copolymer (PLGA), hyaluronic acid, etc.

[0026] Preferably, the dosage form of the drug comprises an injection, a powder, a granule, a capsule, and a tablet.

[0027] Preferably, the administration mode of the drug comprises injection administration and oral administration.

[0028] Compared with the prior art, the present application has the following beneficial effects:

[0029] The treatment of acute myeloid leukemia is still facing severe challenges at home and abroad, and there is no report on the research of small peptides participating in the UPR response of acute myeloid leukemia. The present application first discovers and confirms that a long-chain non-coding RNA PROSER2-AS1 encoded small peptide PEARL has the effect of diagnosis and targeted treatment in acute myeloid leukemia (AML). The present application first detects the leukemia patient samples and leukemia cell lines by qRT-PCR technology, finds that the small peptide PEARL is significantly lowly expressed in acute myeloid leukemia patients, and is relatively highly expressed under normal physiological conditions and in other types of cancers, which indicates that the small peptide can indicate the diagnosis and prognosis of the disease. At the same time, it is found through research that PROSER2-AS1 does not play a role by itself, but plays a function through the encoded small peptide PEARL. Further through the mouse leukemia model experiment, it is found that overexpression of the small peptide PEARL can significantly inhibit the survival of acute myeloid leukemia cells and significantly prolong the survival cycle of the model mice. Finally, through the research on the biological molecular mechanism of the small peptide PEARL, it is found that overexpression of PEARL can increase the endoplasmic reticulum stress of acute myeloid leukemia cells, activate the unfolded protein response (UPR), and directly regulate the stress level of the endoplasmic reticulum of acute myeloid leukemia cells by interacting with the UPR response effector PERK, thereby affecting the function of acute myeloid leukemia cells. Therefore, the present application can provide a new precise judgment or treatment strategy and genetic resource for the diagnosis or targeted treatment of acute myeloid leukemia, and has important theoretical significance and application value. BRIEF DESCRIPTION OF DRAWINGS

[0030] Figure 1 Identification and positioning of the small peptide PEARL encoded by PROSER2-AS1; wherein (A) mass spectrometry detected peptide segment combined with ORFfinder analysis shows that PROSER2-AS1 ORF32 can be encoded by a non-classical initiation codon ACG to start the small peptide PEARL, and the size is 74 amino acids, and the red font is the characteristic peptide segment of the small peptide; (B) identification of the translation ability of PEARL, respectively constructing the small peptide with HA labeled initiation codon ACG mutated to ACA and the normal small peptide; (C) antigen epitope for preparing the polyclonal antibody of the small peptide PEARL; (D) detecting the HA labeled protein by using the prepared antibody; (E) nuclear and cytoplasmic separation shows that the small peptide PEARL is located in the cytoplasm; (F) the result of immunofluorescence shows that the small peptide PEARL is located on the endoplasmic reticulum.

[0031] Figure 2Expression of PROSER2-AS1 / PEARL in acute myeloid leukemia; wherein, (A) GEPIA analysis showed that PROSER2-AS1 / PEARL was specifically lowly expressed in acute myeloid leukemia; (B) qRT-PCR technology detected that the expression level of PROSER2-AS1 / PEARL in acute myeloid leukemia initial diagnosis samples (n=50) was significantly higher than that in normal umbilical cord blood sample group (n=10) (****P<0.0001); (C) qRT-PCR technology detected that the expression of PROSER2-AS1 / PEARL in acute myeloid leukemia cell lines was generally low.

[0032] Figure 3 Effect of PEARL knockdown and overexpression in acute myeloid leukemia; wherein, (A) qRT-PCR technology detected the knockdown effect of PEARL in HL-60; the asterisk indicates that the difference between the two groups has statistical significance by t test (*P<0.05; **P<0.01); (B) After constructing a stable overexpression PEARL cell line, qRT-PCR and western blot technology were used to detect the overexpression of small peptides with HA marker and normal PEARL whose start codon ACG was mutated to ACA (***P<0.001; ****P<0.0001).

[0033] Figure 4 PEARL but not PROSER2-AS1 regulates the cytological function of acute myeloid leukemia; wherein, (A) After overexpression of HA-labeled PEARL, MOLM-13 differentiation was significantly promoted; while after overexpression of HA-labeled small peptides PEARLMut whose start codon ACG was mutated to ACA, MOLM-13 cells were not affected (**P<0.01; ***P<0.001); (B) After knockdown of PROSER2-AS1 / PEARL, MOLM-13 cell apoptosis was significantly inhibited, and cell differentiation was significantly inhibited (**P<0.01; ***P<0.001).

[0034] Figure 5(A) Survival curve statistics of mice after inoculation of MOLM-13 overexpressing PEARL; p value was calculated by log-rank (Mantel-Cox) test (**, p < 0.01); (B) Tail vein model of mice showed that the weight of spleen of mice after inoculation of MOLM-13 overexpressing PEARL was significantly higher than that of the control group inoculated with NC cells (**, p < 0.01); (C) Tail vein model of mice showed that the number of cells in organs (including bone marrow, blood, spleen and liver) of mice after inoculation of MOLM-13 overexpressing PEARL was significantly less than that of the control group inoculated with NC cells; PBS injection was blank control; the average value ± standard deviation of three repeats was used in the figure, and the asterisk indicated that the difference between the two groups was statistically significant by t test (**, p < 0.01; ***, p < 0.001).

[0035] Figure 6 (A) SUnSET experiment showed that overexpression of PEARL inhibited the insertion of puromycin, indicating that the overall translation level of protein was reduced; (B) GO analysis of PEARL interacting proteins showed that PEARL was related to unfolded protein response; (C) Co-immunoprecipitation experiment confirmed that PEARL was closely combined with PERK, an UPR response effector. DETAILED DESCRIPTION

[0036] The specific embodiments of the present application will be further described below. It should be noted that the description of these embodiments is used to help understand the present application, but does not constitute a limitation on the present application. In addition, the technical features involved in each embodiment of the present application described below can be combined with each other as long as they do not conflict with each other.

[0037] The experimental methods in the following examples are all conventional methods unless otherwise specified. The test materials used in the following examples are all commercially available unless otherwise specified.

[0038] Example 1: Identification and localization of small peptide PEARL encoded by PROSER2-AS1

[0039] The present application discovers a lncRNA, which is named as PROSER2-AS1 (ENSG00000225778, NR_038222.1). The gene locus (referring to hg38) of PROSER2-AS1 is located on the antisense DNA strand of human chromosome 10, and the gene coverage ranges from 11,847,213 bp to 11,894,710 bp, which can transcribe a lncRNA with a length of 3163 nt, and the nucleotide sequence is shown as SEQ ID NO: 1. At the same time, the present application newly identifies that there is a short peptide PEARL (A) with 74 amino acids encoded by a non-canonical start codon on the lncRNA, and the sequence is shown as SEQ ID: 2. Figure 1 A), and the sequence is shown as SEQ ID: 2.

[0040] The sequence of PROSER2-AS1 gene (3163 bp, SEQ ID NO: 1):

[0041] > PROSER2-AS1 (ENSG00000225778, NR_038222.1):

[0042]

[0043] PEARL amino acid sequence (74 aa, SEQ ID NO: 2):

[0044] > PEARL

[0045] TQQKGQDTQRRWRTHLGTEGQCDLPGAGGPARAFPEETAKPRPGTAEEKQGGGRRGPVPSSSAVPGGRSARLSA.

[0046] To further verify the existence of the small peptide, primers (SEQ ID NO: 3 and SEQ ID NO: 4) were designed to amplify the small peptide, western blot was used to verify the small peptide, and immunofluorescence technology and confocal microscopy were used to locate the small peptide. In this embodiment, an HA tag was added to the C-terminal of ORF32 (chr10: 11925853-11937442 strand = -) Figure 1 B).

[0047] Forward primer sequence: 5’ACGCAGCAGAAGGGACAAGAC 3’ (SEQ ID NO: 3);

[0048] Reverse primer sequence: 5’CGGAATTCTATGTTTGCTTTGTTTTATTAACTCCTTGGAG 3’ (SEQ ID NO: 4);

[0049] At the same time, a plasmid in which the start codon ACG was mutated to ACA was constructed as a control, and primers (SEQ ID NO: 5 and SEQ ID NO: 6) were designed to amplify and verify by western blot. The western blot results showed that the ORF32 of PROSER2-AS1 can translate the small peptide PEARL, while in the case of mutation of ACG to ACA, the small peptide cannot be expressed.

[0050] Forward primer sequence: 5’ACACAGCAGAAGGGACAAGAC 3’ (SEQ ID NO: 5);

[0051] Reverse primer sequence: 5’CGGAATTCTATGTTTGCTTTGTTTTATTAACTCCTTGGAG 3’ (SEQ ID NO: 6).

[0052] At the same time, to further identify the endogenous expression of the small peptide PEARL, an endogenous antibody was customized according to the characteristic peptide segment of the small peptide Figure 1C), Western blot results showed that, when the small peptide was overexpressed using pCDH-CMV-MCS-EF1-Puro(CD510B-1), the antibody could detect the corresponding trend changes of the small peptide. Figure 1 D), these results demonstrate both the specificity of the customized antibody and the actual presence of the small peptide encoded by PROSER2-AS1 in vivo. Nucleocytoplasmic separation experiments revealed that the small peptide PEARL is primarily located in the cytoplasm. Figure 1 E). Finally, immunofluorescence assays revealed that the small peptide PEARL was localized on the endoplasmic reticulum (E). Figure 1 F).

[0053] Example 2: PEARL expression analysis and its clinical value assessment

[0054] Previous studies of this invention have found that the small peptide PEARL is specifically lowly expressed in acute myeloid leukemia, but highly expressed under normal physiological conditions and in other types of leukemia. Figure 2 (A and C). To further determine the expression specificity of PEARL in acute myeloid leukemia (AML), this embodiment re-collected a batch of bone marrow samples from patients at the First Affiliated Hospital of Sun Yat-sen University for analysis, including 50 newly diagnosed AML samples and 10 normal umbilical cord blood samples. All sample collection was approved by the Ethics Committee of Sun Yat-sen University and informed consent was obtained from the patients. PEARL was specifically detected by extracting RNA and using qRT-PCR technology. The qRT-PCR primers used in this process are as follows:

[0055] Forward primer sequence: 5'CTGGTGGCCTCCTGCTTAC 3' (SEQ ID NO:7);

[0056] Reverse primer sequence: 5'CGTGTCTTGTCCCTTCTGCT 3' (SEQ ID NO:8).

[0057] Experiments revealed that PEARL was significantly underexpressed in acute myeloid leukemia compared to normal umbilical cord blood samples (p<0.001). Figure 2 B), while it is relatively highly expressed under normal physiological conditions and in other types of cancer ( Figure 2 C). This suggests a possible correlation between PEARL expression levels and disease incidence, and that PEARL may indicate the prognosis of acute myeloid leukemia (AML). These results suggest that PEARL has the potential to differentiate AML from normal samples and, to some extent, indicates the prognosis of the disease, suggesting that PEARL overexpression may be a potential treatment for AML.

[0058] Example 3: Functional identification of PEARL in acute myeloid leukemia

[0059] To address the core question of PEARL's role in regulating acute myeloid leukemia (AML), this study aims to further investigate the impact of PEARL on AML function. First, the small peptide PEARL was knocked down using siRNA, and the knockdown effect of PEARL in HL-60 was detected by RT-PCR. Figure 3 A); After constructing a stable PEARL overexpression cell line, qRT-PCR and Western blot were used to detect the expression of HA-labeled start codon ACG-mutated small peptides and normal PEARL (A); Figure 3 B). The identification of whether the functional peptide PEARL or lncRNA PROSER2-AS1 is responsible for differentiation was determined. Experimental studies showed that overexpression of HA-labeled PEARL significantly promoted the differentiation of MOLM-13 cells; however, overexpression of the HA-labeled peptide PEARLMut, with its start codon mutated from ACG to ACA, did not affect MOLM-13 cells. Figure 4 A) This indicates that PEARL functions through protein, not RNA. Furthermore, two different siRNA sequences were designed for PEARL using siRNA interference technology, as shown below:

[0060] The forward sequence of siRNA-1: 5'GGUUGACCUGAGCCUACUU dTdT 3' (SEQ ID NO:9);

[0061] The reverse sequence of siRNA-1: 5'AAGUAGGCUCAGGUCAACC dTdT3' (SEQ ID NO:10);

[0062] The forward sequence of siRNA-2: 5'GCGGAUCGAGGACUGCCUA dTdT 3' (SEQ ID NO:11);

[0063] The reverse sequence of siRNA-2: 3'UAGGCAGUCCUCGAUCCGC dTdT5' (SEQ ID NO:12).

[0064] In the acute myeloid leukemia cell line MOLM-13, after knocking down PEARL cells, apoptosis was detected by flow cytometry. The experimental results are as follows: Figure 4 As shown in Figure B, knocking down PEARL significantly reduced the apoptosis rate. Furthermore, after knocking down PEARL using siRNA interference, cell differentiation was assessed using flow cytometry. The experimental results are as follows: Figure 4C shows that in the case of knocking down PEARL, the differentiation of acute myeloid leukemia cell lines is significantly inhibited. Therefore, it is inferred that PEARL has a potential regulatory effect on the occurrence and development of acute myeloid leukemia.

[0065] Next, the regulatory effect of PEARL on acute myeloid leukemia was further verified at the adult level. Again, a stable expression strain of PEARL overexpression was constructed using a pCDH-CMV-MCS-EF1-Puro (CD510B-1) lentiviral expression system, and MOLM-13 PEARL overexpression cell strains were obtained by puromycin screening. Subsequently, the effective stable MOLM-13 PEARL cell strains were expanded and injected into 5-week-old NOD-SCID mice via the tail vein: a total of 2 groups (NC, PEARL), 10 mice in each group, and PBS was injected as a blank control (1 x 10 6 The animal experiment was approved by the Animal Ethics Committee of Sun Yat-Sen University. Survival curve analysis by Log-rank (Mantel-Cox) Test found that the survival rate of the mice group overexpressing PEARL was higher than that of the control group Figure 5 A). After three weeks of inoculation, the bone marrow, peripheral blood and organs of each group of mice were taken, and the size and weight of the spleen of the PEARL overexpression cell group were significantly higher than those of the NC cell group Figure 5 B). At the same time, human leukemia cell surface markers were labeled with human hCD45 antibody and detected. The flow cytometry results showed that CD45 positive MOLM-13 cells were basically not detected in the PBS group, and the CD45 positive MOLM-13 cells in each organ of the PEARL group mice were significantly less than those in the NC group mice Figure 5 C). The above results show that overexpression of PEARL can inhibit the tumorigenesis of acute myeloid leukemia and affect the growth of leukemia cells, thereby affecting the occurrence and development of acute myeloid leukemia. At the same time, it shows that PEARL may be a potential target for treating acute myeloid leukemia.

[0066] Example 4: PEARL binds to PERK to regulate the endoplasmic reticulum stress level of acute myeloid leukemia cells

[0067] Whether from the cell level or the in vitro mouse experiment, it is confirmed that PEARL can significantly affect the function of acute myeloid leukemia cells. How does PEARL regulate acute myeloid leukemia? To solve this problem, this embodiment uses SUnSET experiment to find that after overexpression of PEARL in MOLM-13 cells, the puromycin-labeled peptide segment is significantly reduced, indicating that overexpression of PEARL can inhibit the translation level of acute myeloid leukemia cells Figure 6A) Further using PEARL interaction protein GO analysis, it is found that PEARL is related to unfolded protein response Figure 6 B) Finally, using immunoprecipitation technology, it is found that PEARL can specifically interact with UPR response effector PERK Figure 6 C) The above results show that after overexpression of PEARL, PEARL directly regulates the stress level of the endoplasmic reticulum of acute myeloid leukemia cells by interacting with the UPR response effector PERK, significantly increases the endoplasmic reticulum stress of acute myeloid leukemia cells, activates the UPR response, thereby inhibiting the translation level of acute myeloid leukemia cells, affecting the function of acute myeloid leukemia cells, and ultimately achieving the effect of affecting the occurrence and development of acute myeloid leukemia.

[0068] As can be seen from the above, the present application first discovers and confirms that a small peptide PEARL based on lncRNA translation is lowly expressed in acute myeloid leukemia, and is relatively highly expressed under normal physiological conditions and in other types of cancer, suggesting that the small peptide can indicate the diagnosis and prognosis of the disease. In addition, the present application also illustrates that PEARL regulates the endoplasmic reticulum stress level of acute myeloid leukemia, and overexpression of PROSER2-AS1 / PEARL can significantly increase the endoplasmic reticulum stress of acute myeloid leukemia cells, activate the UPR response, thereby inducing cell death and improving the survival cycle of the disease. These findings can provide a new theoretical basis for the development of drug action targets for acute myeloid leukemia, and have important application value for the diagnosis and gene-targeted treatment of acute myeloid leukemia.

[0069] The embodiments of the present application are described in detail above, but the present application is not limited to the described embodiments. For those skilled in the art, various changes, modifications, replacements and variations of the embodiments can be made without departing from the principles and spirits of the present application, and still fall within the protection scope of the present application.

Claims

1. Use of a reagent for detecting the expression level of a small peptide PEARL encoded based on lncRNA PROSER2-AS1 in the preparation of an acute myeloid leukemia diagnosis product, characterized in that, The nucleic acid sequence of the lncRNA PROSER2-AS1 is shown as SEQ ID NO: 1, and the amino acid sequence of the small peptide PEARL is shown as SEQ ID NO:

2.

2. Use according to claim 1, characterized in that, The reagent for detecting the expression level of the small peptide PEARL is a primer for detecting the expression amount of the small peptide PEARL, and the sequences are shown as SEQ ID NO: 3-4.

3. Use according to claim 1, characterized in that, The diagnostic product includes a diagnostic chip or kit.

4. Use of a reagent overexpressing a small peptide PEARL coded based on lncRNA PROSER2-AS1 for the preparation of a product for the treatment of acute myeloid leukemia, characterized in that, The nucleic acid sequence of the lncRNA PROSER2-AS1 is shown as SEQ ID NO: 1, and the amino acid sequence of the small peptide PEARL is shown as SEQ ID NO:

2.

5. Use according to claim 4, characterized in that, The reagent inhibits the occurrence and development of acute myeloid leukemia by overexpressing the small peptide PEARL, thereby achieving the treatment of acute myeloid leukemia.

6. Use according to claim 5, characterized in that, The inhibition of the occurrence and development of acute myeloid leukemia is the inhibition of the translation level of acute myeloid leukemia cells.

7. Use according to claim 6, characterized in that, The inhibition of the translation level of acute myeloid leukemia cells significantly increases the endoplasmic reticulum stress of acute myeloid leukemia cells by interacting with the UPR response effector PERK, thereby activating the UPR response.

8. Use according to claim 4, characterized in that, The reagent for overexpressing the small peptide PEARL coded by the lncRNA PROSER2-AS1 includes pCDH-CMV-MCS-EF1-Puro.

9. Use according to claim 6, characterized in that, The acute myeloid leukemia cells include MOLM-13 and HL60.

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