MDS / AML prognosis evaluation model construction method and application thereof

Abstract

The invention relates to a construction method of an MDS / AML prognosis evaluation model, which comprises the following steps: (1) collecting data required by an IPSS-R evaluation system of a patient, and detecting whether TP53, DDX41, WT1, ROBO1 and FLT3-ITD genes in a sample are mutated or not; (2) grouping the IPSS-Rs according to the integral of the IPSS-Rs and assigning the IPSS-Rs; (3) assignment is carried out according to the mutation states of TP53, DDX41, WT1, ROBO1 and FLT3-ITD; (4) substituting the IPSS-R assignment obtained in the step (2) and the assignments corresponding to the various gene mutations obtained in the step (3) into a formula to calculate an MDS / AML-IPSS-M value; and (5) grouping according to the MDS / AML-IPSS-M value calculated in the step (4), and performing prognosis evaluation. The model provided by the invention is used for prognosis evaluation of MDS / AML patients, provides important guidance for subsequent treatment of the patients, and has good clinical application value.

Description

Technical Field

[0001] This invention belongs to the field of biotechnology, specifically relating to a method for constructing an MDS / AML prognostic assessment model. Background Technology

[0002] Myelodysplastic syndromes (MDS) are a group of myeloid clonal / neoplastic diseases originating from hematopoietic stem cells, characterized by abnormal differentiation and development of myeloid cells, manifesting as ineffective hematopoiesis, refractory cytopenia, hematopoietic failure, and a high risk of transformation into acute myeloid leukemia (AML). Approximately half of MDS patients exhibit an increase in peripheral blood and / or bone marrow blasts. According to the previous World Health Organization (WHO) classification, MDS with increased blasts can be divided into MDS-EB1 (5%-9% bone marrow blasts or 2%-4% peripheral blood blasts) and MDS-EB2 (10%-19% bone marrow blasts or 5%-19% peripheral blood blasts). The higher the proportion of blasts, the greater the risk of transformation to AML; the risk of AML transformation in MDS-EB2 patients can reach 30%-50%. MDS / AML is a group of MDS with peripheral blood or bone marrow blasts between 10% and 19% as defined by the 2022 International Consensus Classification (ICC) to emphasize their high risk of transformation to AML, and is a unique population.

[0003] MDS is a highly heterogeneous group of diseases with extremely varied prognoses, with median survival ranging from months to years. Treatment goals and regimens differ depending on the prognostic stratification. Currently, MDS prognostic stratification includes the International Prognostic Score System (IPSS), the revised International Prognostic Score System (IPSS-R), and the WHO phenotypic prognostic score system (WPSS), with IPSS-R being the most widely used in clinical practice. In recent years, the International Prognostic Score System (IPSS-M), which incorporates molecular genetics, has added important driver gene mutations in MDS, providing a more precise understanding of MDS prognostic stratification. However, there is currently no standard prognostic stratification system for MDS / AML patients. Clinically, most analyses rely on the MDS prognostic score system, but this cannot provide precise patient stratification. Therefore, there is an urgent clinical need for a model based on molecular biological alterations to comprehensively assess patient prognosis. Summary of the Invention

[0004] To address the shortcomings of prognostic assessment models for MDS / AML and to meet clinical needs, this invention provides an IPSS (MDS / AML-IPSS-M) prognostic assessment model system incorporating molecular biological alterations, along with its construction method and application, for prognostic assessment of MDS / AML patients and to guide clinical treatment.

[0005] The “MDS / AML” disease of this invention refers to a group of myelodysplastic syndromes (MDS) with peripheral blood or bone marrow blasts ranging from 10% to 19%, as defined by the 2022 International Consensus Classification (ICC). This disease is characterized by a high risk of transformation into acute myeloid leukemia (AML).

[0006] The present invention will achieve the above-mentioned objectives through the following technical solutions: The first aspect of this invention provides a method for constructing an MDS / AML prognostic risk assessment model, the method comprising the following steps: (1) Collect the grouping data of the patient IPSS-R assessment system and detect whether the TP53, DDX41, WT1, ROBO1 and FLT3-ITD genes in the sample are mutated; (2) Scoring the five indicators required by the IPSS-R assessment system collected in step (1), namely, patient hemoglobin level, platelet count, absolute neutrophil count, bone marrow blast cell ratio and chromosome information, respectively, and the sum of the results of the five indicators is used as the IPSS-R score. The IPSS-R score is grouped according to the IPSS-R score and assigned a value to obtain the IPSS-R value. (3) When the five genes detected in step (1) are mutated, assign values ​​to them to obtain the values ​​of TP53, DDX41, WT1, ROBO1 and FLT3-ITD; (4) Substitute the IPSS-R value obtained in step (2) and the TP53, DDX41, WT1, ROBO1 and FLT3-ITD values ​​obtained in step (3) into the following formula to calculate the MDS / AML-IPSS-M value: MDS / AML-IPSS-M=0.556*IPSS-R+1.059*TP53-0.784*DDX41-0.905*WT1+2.11*ROBO1+1.452*FLT3-ITD; (5) Group the MDS / AML-IPSS-M values ​​calculated in step (4) and perform prognostic assessment.

[0007] Preferably, the five indicators in step (2) are scored according to the following rules: Regarding hemoglobin levels: 0 points are awarded when hemoglobin level ≥ 100 g / L; 1 point is awarded when hemoglobin level ≤ 80 g / L < 100 g / L; and 1.5 points are awarded when hemoglobin level < 80 g / L. For platelet count: When the platelet count is ≥100*10 9 / L, 0 points; when 50*10 9 / L≤hemoglobin level<100*10 9 / L, 0.5 points; when platelet count <50*10 9 / L, 1 point; For absolute neutrophil count: when the absolute neutrophil count is ≥0.8*10 9 / L, 0 points; when the absolute neutrophil count is <0.8*10 9 / L, 0.5 points; Regarding the proportion of bone marrow blast cells: 0 points are awarded when the proportion of bone marrow blast cells is ≤2%; 1 point is awarded when 2% < proportion of bone marrow blast cells < 5%; 2 points are awarded when 5% ≤ proportion of bone marrow blast cells ≤ 10%; and 3 points are awarded when the proportion of bone marrow blast cells > 10%. For chromosome information: 0 points for -Y or del(11q); 1 point for Normal or del(5q) or del(12p) or del(20q) or 5q; 2 points for del(7q) or +8 or +19 or i(17q) or other abnormalities of one or two independent clones; 3 points for -7 or inv(3) / t(3q) / del(3q) or -7 / del(7q) with another abnormality or complex karyotypes of three clones; 4 points for complex karyotypes with more than three clones.

[0008] Preferably, the assignment rule for the IPSS-R integral in step (2) is as follows: IPSS-R score ≤ 1.5 indicates very low risk (IPSS-R = 1); 1.5 < IPSS-R score ≤ 3 indicates low risk (IPSS-R = 2); 3 < IPSS-R score ≤ 4.5 indicates medium risk (IPSS-R = 3); 4.5 < IPSS-R score ≤ 6 indicates high risk (IPSS-R = 4); IPSS-R score > 6 indicates very high risk (IPSS-R = 5).

[0009] Preferably, the assignment rules for the five genes in step (3) when mutation occurs are as follows: if the TP53 gene mutates, TP53=1, otherwise TP53=0; if the DDX41 gene mutates, DDX41=1, otherwise DDX41=0; if the WT1 gene mutates, WT1=1, otherwise WT1=0; if the ROBO1 gene mutates, ROBO1=1, otherwise ROBO1=0; if the FLT3-ITD gene mutates, FLT3-ITD=1, otherwise FLT3-ITD=0.

[0010] Preferably, the criteria for judging the prognosis of subjects in step (5) are as follows: MDS / AML-IPSS-M value ≤1 is low-risk group, 1 < MDS / AML-IPSS-M value ≤1.5 is low-intermediate-risk group, 1.5 < MDS / AML-IPSS-M value ≤3 is high-intermediate-risk group, and MDS / AML-IPSS-M value >3 is high-risk group.

[0011] Preferably, the prognostic assessment model is used to predict and assess the overall survival of the subjects.

[0012] Preferably, the prognostic assessment model is used to predict and assess the leukemia-free survival of the subjects.

[0013] A second aspect of the present invention provides an MDS / AML prognostic risk assessment system, the prognostic risk assessment system comprising: (1) Analysis module: The analysis module is used to obtain data related to the subject's IPSS-R score, as well as data on gene mutations in TP53, DDX41, WT1, ROBO1 and FLT3-ITD; (2) Assessment module: The assessment module scores based on the obtained IPSS-R score data, and uses the sum of the scores of the five indicators as the IPSS-R score. The IPSS-R scores are grouped and assigned values. Then, the gene mutation data are assigned their corresponding assessment scores. The obtained IPSS-R scores and the gene mutation data scores are substituted into the MDS / AML-IPSS-M calculation formula to calculate the total MDS / AML-IPSS-M score. Finally, the prognostic status of the subject is output to realize the MDS / AML prognostic risk assessment of the subject.

[0014] Preferably, the IPSS-R score-related data in the analysis module includes the patient's hemoglobin level, platelet count, absolute neutrophil count, bone marrow blast cell ratio, and chromosome information.

[0015] Preferably, the scoring rules for IPSS-R score-related data in the evaluation module are as follows: Regarding hemoglobin levels: 0 points are awarded when hemoglobin level ≥ 100 g / L; 1 point is awarded when hemoglobin level ≤ 80 g / L < 100 g / L; and 1.5 points are awarded when hemoglobin level < 80 g / L. For platelet count: When the platelet count is ≥100*10 9 / L, 0 points; when 50*10 9 / L≤hemoglobin level<100*10 9 / L, 0.5 points; when platelet count <50*10 9 / L, 1 point; For absolute neutrophil count: when the absolute neutrophil count is ≥0.8*10 9 / L, 0 points; when the absolute neutrophil count is <0.8*10 9 / L, 0.5 points; Regarding the proportion of bone marrow blast cells: 0 points are awarded when the proportion of bone marrow blast cells is ≤2%; 1 point is awarded when 2% < proportion of bone marrow blast cells < 5%; 2 points are awarded when 5% ≤ proportion of bone marrow blast cells ≤ 10%; and 3 points are awarded when the proportion of bone marrow blast cells > 10%. For chromosome information: 0 points for -Y or del(11q); 1 point for Normal or del(5q) or del(12p) or del(20q) or 5q; 2 points for del(7q) or +8 or +19 or i(17q) or other abnormalities of one or two independent clones; 3 points for -7 or inv(3) / t(3q) / del(3q) or -7 / del(7q) with another abnormality or a complex karyotype of three abnormalities; 4 points for a complex karyotype with more than three abnormalities.

[0016] Preferably, the assignment rules for the IPSS-R integral in the evaluation module are as follows: IPSS-R score ≤ 1.5 indicates very low risk (IPSS-R = 1); 1.5 < IPSS-R score ≤ 3 indicates low risk (IPSS-R = 2); 3 < IPSS-R score ≤ 4.5 indicates medium risk (IPSS-R = 3); 4.5 < IPSS-R score ≤ 6 indicates high risk (IPSS-R = 4); IPSS-R score > 6 indicates very high risk (IPSS-R = 5).

[0017] Preferably, the assignment rules for gene mutation data in the evaluation module are as follows: If the TP53 gene is mutated, TP53=1; otherwise, TP53=0. If the DDX41 gene is mutated, DDX41=1; otherwise, DDX41=0. If the WT1 gene is mutated, WT1=1; otherwise, WT1=0. If the ROBO1 gene is mutated, ROBO1=1; otherwise, ROBO1=0. If the FLT3-ITD gene is mutated, FLT3-ITD=1; otherwise, FLT3-ITD=0.

[0018] Preferably, the formula for calculating the total score MDS / AML-IPSS-M in the evaluation module is as follows: MDS / AML-IPSS-M=0.556*IPSS-R+1.059*TP53-0.784*DDX41-0.905*WT1+2.11*ROBO1+1.452*FLT3-ITD.

[0019] Preferably, the evaluation criteria for the prognostic status of subjects in the assessment module are as follows: MDS / AML-IPSS-M value ≤ 1 is low-risk group, 1 < MDS / AML-IPSS-M value ≤ 1.5 is low-intermediate-risk group, 1.5 < MDS / AML-IPSS-M value ≤ 3 is high-intermediate-risk group, and MDS / AML-IPSS-M value > 3 is high-risk group.

[0020] A third aspect of the present invention provides a gene composition for prognostic risk assessment of MDS / AML, said gene composition being composed of mutated TP53, DDX41, WT1, ROBO1 and FLT3-ITD genes.

[0021] A fourth aspect of the present invention provides the use of a reagent for detecting gene expression levels in a gene composition in the preparation of a kit for prognostic risk assessment of MDS / AML, said gene composition being composed of mutated TP53, DDX41, WT1, ROBO1 and FLT3-ITD genes.

[0022] The beneficial effects of this invention are: This invention combines IPSS-R and gene mutation to construct a prognostic model for MDS / AML, which fully integrates the patient's clinical characteristics and molecular mutation characteristics, providing important guidance for the subsequent treatment of MDS / AML patients and has good clinical application value. Attached Figure Description

[0023] Figure 1 The impact of the MDS / AML-IPSS-M model on the prognostic survival of MDS / AML patients, among which Figure 1 'a' represents the impact on overall survival. Figure 1 b indicates the impact on leukemia-free survival; Figure 2 The impact of IPSS-R and IPSS-M models on prognostic survival in MDS / AML patients, among which Figure 2 'a' represents the impact of the IPSS-R model on the overall survival of MDS / AML patients. Figure 2 b represents the impact of the IPSS-R model on leukemia-free survival in MDS / AML patients; Figure 2 c represents the impact of the IPSS-M model on the overall survival of MDS / AML patients. Figure 2 d represents the impact of the IPSS-M model on leukemia-free survival in MDS / AML patients; Figure 3 To compare the prognostic efficacy of the IPSS-M model, IPSS-R model, and IPSS-M model for MDS / AML patients based on the C-index; Figure 4To compare the prognostic efficacy of the MDS / AML-IPSS-M model with the IPSS-R model and the IPSS-M model for MDS / AML patients using ROC curves; Figure 5 To verify the impact of the MDS / AML-IPSS-M model on the prognosis of MDS / AML patients based on the data of this invention; Figure 6 To screen the impact of the MDS / AML-IPSS-M comparative model on the prognostic survival of MDS / AML patients in the trial, among which Figure 6 'a' represents the impact on overall survival. Figure 6 b represents the impact on leukemia-free survival. Detailed Implementation

[0024] Experimental Example 1: Construction of the MDS / AML Prognostic Assessment Model Step 1: Download the clinical and genetic mutation data of MDS cases (MDS IWG, IPSSM, NEJM Evidence 2022) from the Cancer Genome Atlas (TCGA) database through the cBioPortal website (https: / / www.cbioportal.org / ), screen patients who meet the diagnosis of MDS / AML, and finally include 374 cases. Import all patients' clinical information data into the Social Science Statistical Suite (SPSS).

[0025] Step 2: Using SPSS statistical software, enter the analysis module through Analysis → Survival Functions → Cox Regression. Include overall survival time in the time field and survival status in the status field. Also include each gene mutation and IPSS-R grouping individual variable in the covariate field. Perform Cox univariate regression analysis on the impact of all variables on overall patient survival. The specific results are shown in Table 1.

[0026] Table 1. Cox univariate regression analysis of the impact of different variables on overall survival of MDS / AML patients. Step 3: Based on the Cox univariate regression analysis results in Step 2, select the variables IPSS-R and TP53, DDX41, WT1, ROBO1, and FLT3-ITD gene mutations that have a significant impact on overall survival in the model. Assign values ​​to each variable based on the regression coefficients in the Cox analysis, and calculate the MDS / AML-IPSS-M value for patients using the following formula: MDS / AML-IPSS-M=0.556*IPSS-R+1.059*TP53-0.784*DDX41-0.905*WT1+2.11*ROBO1+1.452*FLT3-ITD; where, if a gene is mutated, the gene is assigned a value of 1, otherwise the gene is assigned a value of 0.

[0027] Step 4: Based on the calculation results of MDS / AML-IPSS-M values, patients are divided into 4 groups: a calculation result ≤1 is the low-risk group, 1 < calculation result ≤1.5 is the low-intermediate-risk group, 1.5 < calculation result ≤3 is the high-intermediate-risk group, and a result >3 is the high-risk group.

[0028] Step 5: Using SPSS statistical software, access the analysis module via Analyze → Survival Functions → Kaplan-Meier. Include survival time in the time frame and survival status in the status frame, while also including MDS / AML-IPSS-M grouping in the factor frame. Additionally, access the analysis module via Analyze → Survival Functions → Kaplan-Meier, including leukemia-free survival time in the time frame and survival status in the status frame, while also including MDS / AML-IPSS-M grouping in the factor frame. Analyze the impact of MDS / AML-IPSS-M on overall patient survival and leukemia-free survival using Kaplan-Meier survival curves. Specific trial results are as follows: Figure 1 As shown in the figure. Experimental results indicate that the MDS / AML-IPSS-M model constructed in this invention can effectively differentiate the prognosis of MDS / AML patients.

[0029] Experimental Example 2: Performance Comparison of MDS / AML Prognostic Assessment Models Step 1: Following the method in Step 5 of Experiment 1, analyze the impact of currently used clinical IPSS-R and IPSS-M model groupings for MDS patients (without distinguishing specific subtypes) on overall survival and leukemia-free survival using Kaplan-Meier survival curves (IPSS-R model grouping is the same as the IPSS-R model part of the MDS / AML-IPSS-M formula in Experiment 1. IPSS-M model grouping is calculated based on the IPSS-M Risk Calculator constructed from clinical data of unsubtyped MDS patients, available at https: / / www.mds-risk-model.com / ). The results show that the prognostic discrimination of both the IPSS-R and IPSS-M models is inferior to that of the MDS / AML-IPSS-M model (see...). Figure 2 ).

[0030] Step 2: C-index calculation revealed that the MDS / AML-IPSS-M grouping showed higher consistency in prognostic assessment than the IPSS-R and IPSS-M groupings (see...). Figure 3 Furthermore, ROC curve analysis revealed that the overall survival rates at 1, 3, and 5 years were significantly higher in the MDS / AML-IPSS-M group than in the IPSS-R and IPSS-M groups (see [link to analysis]). Figure 4 ).

[0031] Experiment 3: Validation of the MDS / AML prognostic assessment model Forty MDS / AML samples were selected from patients collected at Zhenjiang First People's Hospital from June 2018 to May 2025. Grouping data from the IPSS-R assessment system were collected, and mutations in the TP53, DDX41, WT1, ROBO1, and FLT3-ITD genes were detected. Integrals were calculated using the MDS / AML-IPSS-M model for parallel grouping. Based on SPSS statistical software, the analysis module was accessed via Analysis → Survival Functions → Kaplan-Meier, incorporating survival time into the time frame, survival status into the status frame, and MDS / AML-IPSS-M grouping into the factor frame. The impact of MDS / AML-IPSS-M on patient prognosis was analyzed using Kaplan-Meier survival curves. Figure 5 As shown, the experimental results revealed that the MDS / AML-IPSS-M of the present invention has good prognostic discrimination.

[0032] Experiment 4: Screening Experiment for Mutant Genes in MDS / AML Prognostic Assessment Model Step 1: As described in Step 2 of Experiment Example 1, the impact of IPSS-R grouping and gene mutation on patient prognosis was analyzed using Cox univariate regression analysis to screen variables that had a significant impact on the prognosis of MDS / AML patients (see Table 2). P <0.2 was the cutoff value. IPSS-R grouping and mutation variables of TP53, NOTCH1, DDX41, SMG1, ROBO1, ATRX, DICER1, FLT3-ITD, KDM5C, MPL, SH2B3, JARID2, FLT3, KMT2D, WT1, DNMT3A, IDH1, ARID2, NSD2, GATA2, and CREBBP were included in Cox regression multivariate analysis. Specifically, the analysis module was accessed through Analysis → Survival Function → Cox Regression. Survival time was included in the time category, survival status was included in the status category, and the above variables were also included in the covariate category. Cox multivariate regression analysis was performed to analyze the impact of all variables on patient prognosis. The specific results are shown in Table 3.

[0033] Table 2. Effects of different variables on overall survival of MDS / AML patients in Cox multivariate regression analysis. Step 2: Combining the results of the Cox multivariate regression analysis in Step 1, select the variables that have a significant impact on overall survival: IPSS-R grouping and gene mutations in TP53, NOTCH1, DDX41, SMG1, ROBO1, ATRX, DICER1, FLT3-ITD, and KDM5C. Assign values ​​to each variable based on the regression coefficients in the Cox multivariate analysis, and calculate the MDS / AML-IPSS-M score for each patient using the following formula: MDS / AML-IPSS-M Comparison Model = 0.454*IPSS-R+0.850*TP53+0.646*NOTCH1-0.645*DDX41+0.913*SMG1+2.384*ROBO1+1.699*ATRX+1.736*DICER1+1.804*FLT3-ITD-1.155*KDM5C; where the gene is assigned a value of 1 when a mutation occurs, and a value of 0 otherwise.

[0034] Step 3: Based on the calculation results of the MDS / AML-IPSS-M comparison model, patients are divided into 4 groups: calculation result ≤ 0.5 is the low-risk group, 0.5 < calculation result ≤ 1 is the low-intermediate-risk group, 1 < calculation result ≤ 2 is the high-intermediate-risk group, and calculation result > 2 is the high-risk group.

[0035] Step 4: Using SPSS statistical software, access the analysis module via Analyze → Survival Functions → Kaplan-Meier. Include survival time in the time frame and survival status in the status frame. Simultaneously, include the MDS / AML-IPSS-M grouping in the factor frame. Analyze the impact of MDS / AML-IPSS-M versus Model 1 on overall patient survival using Kaplan-Meier survival curves. The experimental results are as follows: Figure 6 As shown. Experimental results indicate that, based on the Kaplan-Meier survival curve test values, the MDS / AML-IPSS-M comparative model has a lower discrimination capability than the MDS / AML-IPSS-M model of this invention.

[0036] In summary, this invention establishes the MDS / AML-IPSS-M prognostic assessment model, which serves as a method for prognostic assessment of MDS / AML patients, providing clinical support for precise and individualized treatment of MDS / AML patients.

[0037] Although specific embodiments of the invention have been described, those skilled in the art will recognize that various changes and modifications can be made to the invention without departing from its scope or spirit. Therefore, the invention is intended to cover all such changes and modifications falling within the scope of the appended claims and their equivalents.

Claims

1. A method for constructing an MDS / AML prognostic risk assessment model, characterized in that, The construction method includes the following steps: (1) Collect the grouping data of the patient IPSS-R assessment system and detect whether the TP53, DDX41, WT1, ROBO1 and FLT3-ITD genes in the sample are mutated; (2) Scoring the five indicators required by the IPSS-R assessment system collected in step (1), namely, patient hemoglobin level, platelet count, absolute neutrophil count, bone marrow blast cell ratio and chromosome information, respectively, and the sum of the results of the five indicators is used as the IPSS-R score. The IPSS-R score is grouped according to the IPSS-R score and assigned a value to obtain the IPSS-R value. (3) When the five genes detected in step (1) are mutated, assign values ​​to them to obtain the values ​​of TP53, DDX41, WT1, ROBO1 and FLT3-ITD; (4) Substitute the IPSS-R value obtained in step (2) and the TP53, DDX41, WT1, ROBO1 and FLT3-ITD values ​​obtained in step (3) into the following formula to calculate the MDS / AML-IPSS-M value: MDS / AML-IPSS-M=0.556*IPSS-R+1.059*TP53-0.784*DDX41-0.905*WT1+2.11*ROBO1+1.452*FLT3-ITD; (5) Group the MDS / AML-IPSS-M values ​​calculated in step (4) and perform prognostic assessment.

2. The construction method according to claim 1, characterized in that, The five indicators in step (2) are scored according to the following rules: Regarding hemoglobin levels: 0 points are awarded when hemoglobin level ≥ 100 g / L; 1 point is awarded when hemoglobin level ≤ 80 g / L < 100 g / L; and 1.5 points are awarded when hemoglobin level < 80 g / L. For platelet count: When the platelet count is ≥100*10 9 / L, 0 points; when 50*10 9 / L≤hemoglobin level<100*10 9 / L, 0.5 points; when platelet count <50*10 9 / L, 1 point; For absolute neutrophil count: when the absolute neutrophil count is ≥0.8*10 9 / L, 0 points; when the absolute neutrophil count is <0.8*10 9 / L, 0.5 points; Regarding the proportion of bone marrow blast cells: 0 points are awarded when the proportion of bone marrow blast cells is ≤2%; 1 point is awarded when 2% < proportion of bone marrow blast cells < 5%; 2 points are awarded when 5% ≤ proportion of bone marrow blast cells ≤ 10%; and 3 points are awarded when the proportion of bone marrow blast cells > 10%. For chromosome information: 0 points for -Y or del(11q); 1 point for Normal or del(5q) or del(12p) or del(20q) or 5q; 2 points for del(7q) or +8 or +19 or i(17q) or other abnormalities of one or two independent clones; 3 points for -7 or inv(3) / t(3q) / del(3q) or -7 / del(7q) with another abnormality or complex karyotypes of three clones; 4 points for complex karyotypes with more than three clones.

3. The construction method according to claim 1, characterized in that, The rules for assigning values ​​to the IPSS-R integral in step (2) are as follows: IPSS-R score ≤ 1.5 indicates very low risk (IPSS-R = 1); 1.5 < IPSS-R score ≤ 3 indicates low risk (IPSS-R = 2); 3 < IPSS-R score ≤ 4.5 indicates medium risk (IPSS-R = 3); 4.5 < IPSS-R score ≤ 6 indicates high risk (IPSS-R = 4); IPSS-R score > 6 indicates very high risk (IPSS-R = 5).

4. The construction method according to claim 1, characterized in that, The assignment rules for the five genes in step (3) when they mutate are as follows: if the TP53 gene mutates, TP53=1, otherwise TP53=0; if the DDX41 gene mutates, DDX41=1, otherwise DDX41=0; if the WT1 gene mutates, WT1=1, otherwise WT1=0; if the ROBO1 gene mutates, ROBO1=1, otherwise ROBO1=0; if the FLT3-ITD gene mutates, FLT3-ITD=1, otherwise FLT3-ITD=0.

5. The construction method according to claim 1, characterized in that, The criteria for judging the prognosis of subjects in step (5) are as follows: MDS / AML-IPSS-M value ≤1 is low-risk group, 1 < MDS / AML-IPSS-M value ≤1.5 is low-intermediate-risk group, 1.5 < MDS / AML-IPSS-M value ≤3 is high-intermediate-risk group, and MDS / AML-IPSS-M value >3 is high-risk group.

6. A prognostic risk assessment system for MDS / AML, characterized in that, The prognostic risk assessment system includes: (1) Analysis module: The analysis module is used to obtain data related to the subject's IPSS-R score, as well as data on gene mutations in TP53, DDX41, WT1, ROBO1 and FLT3-ITD; (2) Assessment module: The assessment module scores based on the obtained IPSS-R score data, and uses the sum of the scores of the five indicators as the IPSS-R score. The IPSS-R scores are grouped and assigned values. Then, the gene mutation data are assigned their corresponding assessment scores. The obtained IPSS-R scores and the gene mutation data scores are substituted into the MDS / AML-IPSS-M calculation formula to calculate the total MDS / AML-IPSS-M score. Finally, the prognostic status of the subject is output to realize the MDS / AML prognostic risk assessment of the subject.

7. The evaluation system according to claim 6, characterized in that, The analysis module includes data related to the subject's IPSS-R score, such as hemoglobin level, platelet count, absolute neutrophil count, bone marrow blast cell ratio, and chromosome information. The scoring rules for the IPSS-R score-related data in the assessment module are as follows: Regarding hemoglobin levels: 0 points are awarded when hemoglobin level ≥ 100 g / L; 1 point is awarded when hemoglobin level ≤ 80 g / L < 100 g / L; and 1.5 points are awarded when hemoglobin level < 80 g / L. For platelet count: When the platelet count is ≥100*10 9 / L, 0 points; when 50*10 9 / L≤hemoglobin level<100*10 9 / L, 0.5 points; when platelet count <50*10 9 / L, 1 point; For absolute neutrophil count: when the absolute neutrophil count is ≥0.8*10 9 / L, 0 points; when the absolute neutrophil count is <0.8*10 9 / L, 0.5 points; Regarding the proportion of bone marrow blast cells: 0 points are awarded when the proportion of bone marrow blast cells is ≤2%; 1 point is awarded when 2% < proportion of bone marrow blast cells < 5%; 2 points are awarded when 5% ≤ proportion of bone marrow blast cells ≤ 10%; and 3 points are awarded when the proportion of bone marrow blast cells > 10%. For chromosome information: 0 points for -Y or del(11q); 1 point for Normal or del(5q) or del(12p) or del(20q) or 5q; 2 points for del(7q) or +8 or +19 or i(17q) or other abnormalities of one or two independent clones; 3 points for -7 or inv(3) / t(3q) / del(3q) or -7 / del(7q) with another abnormality or a complex karyotype of three abnormalities; 4 points for a complex karyotype with more than three abnormalities.

8. The evaluation system according to claim 6, characterized in that, The formula for calculating the total score MDS / AML-IPSS-M in the evaluation module is as follows: MDS / AML-IPSS-M=0.556*IPSS-R+1.059*TP53-0.784*DDX41-0.905*WT1+2.11*ROBO1+1.452*FLT3-ITD.

9. A gene composition for prognostic risk assessment of MDS / AML, said gene composition being composed of mutated TP53, DDX41, WT1, ROBO1 and FLT3-ITD genes.

10. The use of a reagent for detecting gene expression levels of a gene composition in the preparation of a kit for prognostic risk assessment of MDS / AML, said gene composition being composed of mutated TP53, DDX41, WT1, ROBO1 and FLT3-ITD genes.

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