The Efficacy and Safety of Selinisole Combined With Azacitidine and Venetoclax in the Treatment of Newly Diagnosed High-risk Myeloid Tumors With TP53 Mutations

Inclusion Criteria: 1. Age ≥18 years old; Gender is not limited. 2. The presence of TP53 mutations (According to the 5th Edition of the WHO Classification of hematopoietic and lymphoid tumors and the International Consensus Classification (ICC 2022), the definition of myeloid tumors with TP53 mutations is: pathogenic/potentially pathogenic variations of the TP53 gene are detected through molecular technologies such as next-generation sequencing (NGS), and any of the following conditions are met: The frequency of variant alleles (VAF) is ≥10%, or there are multiple TP53 mutations (≥2 mutations), or both TP53 mutations and 17p deletion (del(17p)) are present. 3. For the initial treatment of myeloid tumors, the diagnosis was made through peripheral blood and bone marrow examinations and exclusion tests (according to the fifth edition of the WHO and ICC consensus） : 3.1 MDS (IPSS-R/IPSS-M at high risk or above; or complex karyotype/alone -5/-5q, -7/-7q, i (17q), inv (3)/t(3;3); Or bone marrow blasts ≥10%; 3.2 AML (bone marrow/peripheral blood blasts ≥20%; and high-risk cytogenetic or molecular abnormalities exist); 3.3 MPN (High risk score above threat; or presence of any one of ASXL1, SRSF2, EZH2, IDH1/2, or U2AF1 gene mutations; or bone marrow blasts ≥10%); 3.4 MDS/MPN (IPSS-R high-risk or above; or bone marrow blast granulocytes ≥10%). 4. Voluntarily join this study, sign the informed consent form with good compliance, and be willing to cooperate with regular follow-ups for efficacy evaluation and side effect monitoring. 5. Before treatment, the patient's total bilirubin (TBIL) was less than 1.5 times the upper limit of the normal value (ULN), and the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were less than 3 times the ULN. 6. ECOG score ≤2 points. Exclusion Criteria: 1. Patients who have transplant plans within three months; 2. All laboratory or clinical records of HIV infection, previous clinical history of hepatitis C, previous hepatitis B infection, or evidence of active hepatitis during screening. Laboratory tests during the screening period suggest hepatitis C infection or hepatitis B infection. (Defined as a positive HBsAg test. Additionally, if the HBsAg test is negative but HBcAb is positive, regardless of the HBsAb status, HBV DNA testing is required. If it is positive, the subject should be excluded.) 3. Suffering from mental disorders or other conditions and unable to cooperate with the requirements of research, treatment and monitoring; 4. Pregnant patients or those who cannot take appropriate contraceptive measures during the treatment period; 5. Those suspected of being allergic to the experimental drug or any of its excipients; 6. Active heart disease is defined as one or more of the following: ① A history of uncontrolled or symptomatic angina pectoris; ② Myocardial infarction less than 6 months from the time of enrollment in the study; ③ There is a history of arrhythmia that requires drug treatment or has severe clinical symptoms; ④ Uncontrolled or symptomatic congestive heart failure (NYHA grade 2) ⑤ The ejection fraction is lower than the lower limit of the normal range. 7. Patients who the researchers consider unsuitable to participate in this trial, such as those whose safety or compliance with the study procedures may be affected by any other medical, social or psychological factors.