CN-122025191-A - Chronic granulomonocytic leukemia risk layering evaluation model and application

Abstract

The invention belongs to the technical field of biological information and biomarkers, and relates to a chronic granulocytic leukemia risk layering evaluation model and application thereof. The model is calculated by taking a biomarker as an input variable, wherein the biomarker consists of peripheral blood platelet count, chromosome, U2AF1 gene, ASXL1_exo12_ 19721ul gene and SF3B1 gene mutation. The risk assessment model constructed by the invention is based on Chinese crowd data, a new CMML patient risk layering model is constructed, the method is simple and efficient, the prediction efficiency is good, and the pain points of poor applicability to Chinese crowd and weak treatment guidance effect in the traditional model are solved. The patient risk is innovatively divided into two types of 'standard risk' and 'high risk', and the simplified design eliminates a decision fuzzy zone between 'observation waiting' and 'overstreating' in the traditional model, so that the clinical guidance effect is achieved.

Inventors

• ZHANG XIAOLIN
• LI YANG
• FANG CHAO

Assignees

• 山东大学齐鲁医院

Dates

Publication Date

20260512

Application Date

20260414

Claims (4)

1. 1. A layering evaluation model for the risk of chronic myelomonocytic leukemia is characterized in that the model is constructed by taking biomarker detection conditions as input variables, wherein the biomarker detection conditions consist of peripheral blood platelet count, chromosome, U2AF1 gene, ASXL1_exo12_ 19721ul gene and SF3B1 gene mutation.
2. 2. The model of claim 1, wherein the model uses a formula to calculate a risk score of = (0.69 x peripheral platelet count corresponding score) + (0.22 x chromosome change corresponding score) + (0.64 x U2AF1 gene mutation corresponding score) + (1.37 x SF3B1 gene mutation corresponding score) + (0.75 x asxl1_exon12_19721ul gene mutation corresponding score), wherein the peripheral platelet count is equal to or greater than 100 x 10 9 /L at 0 score, 20 x 10 9 /L < peripheral platelet count is equal to or less than 100 x 10 9 /L at 1 score, the peripheral platelet count is equal to or less than 20 x 10 9 /L at 2 score, the chromosome normal, -Y is equal to 0 score, -7, -5, +8, the complex nucleus is equal to or greater than 3 abnormalities are equal to or equal to 2 score, the chromosome change is equal to 1 score, asxl1_exon12_19721 is equal to or greater than 0 score, the asxl1_exon12_19721ul gene mutation is equal to or less than 1 score, no mutation is 1 score is present at 1 score, no mutation is present at 1 score is equal to 1 score.
3. 3. The model of claim 2, wherein the CMML prognosis is at risk when the risk score is less than or equal to 1, and the CMML prognosis is at high risk when the risk score is > 1.
4. 4. A set of chronic myelomonocytic leukemia prognosis risk markers, which are characterized by comprising mutations in peripheral blood platelets, chromosomes, the U2AF1 gene, the asxl1_exo12_ 19721ul gene, and the SF3B1 gene.

Description

Chronic granulomonocytic leukemia risk layering evaluation model and application Technical Field The invention belongs to the technical field of biological information and biomarkers, and relates to a chronic myelomonocytic leukemia (CMML) risk layering evaluation model and application thereof. Background Chronic myelomonocytic leukemia (Chronic myelomonocytic leukemia, CMML) is a malignant clonal disease characterized by both myelodysplastic syndrome and myeloproliferative neoplasms, with highly heterogeneous clinical manifestations and prognosis. The disease is a rare malignant disease of the blood system, the incidence rate is about 0.4-1 cases/100000 persons/year, and the disease is mostly old people. CMML patients have a large difference in survival, and some patients only need to be observed for follow-up or oral medication after diagnosis, while some patients need to initiate demethylation therapy or even hematopoietic stem cell transplantation. Currently, CMML patients are not given a proprietary, objective scoring system to initiate treatment. Clinical decisions mainly depend on prognosis layering auxiliary judgment, common prognosis models comprise IPSS, CPSS, CPSS-Mol, a Mayo molecular model, iCPSS and the like, but the area under a working characteristic curve (Area Under the ROC Curve, AUC) of a subject is only about 0.65, and the prediction efficiency is still not ideal. The existing scoring systems are various in variety and different in standard, and are established based on European and American crowd data, so that clinical selection is difficult. For example, CPSS-Mol only incorporates 4 gene mutations, whereas iCPSS covers 10, and each system lacks uniform criteria for weighting parameters such as primary cell proportion, chromosomal abnormalities, etc. In addition, these models are not well-suited for particular populations (e.g., combined myelofibrosis or oligomonocytic CMML), have limited guidance for treatment decisions-most useful for predicting survival and leukemia transformation risk, and it is difficult to develop clear decision guidance, especially for "medium risk" patients with or without treatment, that still requires clinical experience. Therefore, for the patient diagnosed with CMML, there is a need for a risk stratification prognosis scoring system and model based on the data of the chinese population, with universality, high efficiency and accuracy, so as to provide a new reference for the development of related products for assisting in determining the start timing of treatment. Disclosure of Invention Aiming at the problems existing in the traditional CMML prognosis model, the invention provides a chronic granulocytic leukemia risk layering evaluation model and application thereof. In order to achieve the above purpose, the invention is realized by adopting the following technical scheme: A layering evaluation model of the risk of chronic myelomonocytic leukemia is constructed by taking biomarker detection conditions as input variables, wherein the biomarker detection conditions consist of peripheral blood platelet count, chromosome, U2AF1 gene, ASXL1_exo12_ 19721ul gene and SF3B1 gene mutation. Preferably, the model uses the formula risk score = (0.69×peripheral blood platelet count) + (0.22×chromosome change corresponding score) + (0.64×u2af1 gene mutation corresponding score) + (1.37×sf3B1 gene mutation corresponding score) + (0.75×asxl1_exon12_19721ul gene mutation corresponding score). Wherein the number of peripheral blood platelets is more than or equal to 100 multiplied by 10 9/L and is 0, the number of peripheral blood platelets is between 20 and 100 multiplied by 10 9/L and is 1 (not including the end point value), the number of peripheral blood platelets is less than or equal to 20 multiplied by 10 9/L and is 2, the number of normal chromosomes, -Y is 0, -7, -5, +8 and the number of complex karyotypes (more than or equal to 3) are 2, except that the change of the chromosomes is 1, the ASXL1_exO12_ 19721ul gene is not mutated to 0, the mutation is 1, the U2AF1 gene is not mutated to 0, the mutation is 1, the SF3B1 gene is not mutated to 0, and the mutation is 1. When the risk score is less than or equal to 1, the CMML prognosis is the standard risk, and when the risk score is more than 1, the CMML prognosis is the high risk. In another aspect, the invention provides a marker for prognosis risk of chronic myelomonocytic leukemia, which consists of peripheral blood platelets, chromosomes, a U2AF1 gene, an ASXL1_exo12_ 19721ul gene and an SF3B1 gene. The application process of the model comprises the steps of collecting peripheral blood, performing bone marrow puncture and bone marrow fluid gene detection on a primarily treated CMML patient, and synchronously collecting core indexes of the patient, including peripheral blood platelet count, chromosome and mutation detection conditions of specific genes, namely U2AF1 gene, ASXL1_exo12_ 19721ul gene and SF3B1 gene.