1. Part I, Lead-in phase and Part II, Cohort A:

   Patients with relapsed and/or refractory AML Patients with high-risk MDS/AML who have had prior therapy will also be included

2. Part II, Cohort B

   Patients with untreated, newly diagnosed AML of the following subtypes:

   • AML-M6 or AML-M7 by FAB or having erythroid or megakaryocytic differentiation by WHO 2022 classification
   • High-risk MDS/AML with erythroid differentiation and no prior therapy
   • AML with MECOM rearrangement, including, but not limited to t(3;3), inv(3q), confirmed by conventional karyotype or FISH for MECOM rearrangement.

3. Age >/= 18 years. Because no dosing or adverse event data are currently available on the use of APG1252 in combination with AZA in patients <18 years of age, children are not included in this study at this time.

4. Adequate organ function as defined below:

   Liver function (bilirubin < 2mg/dL, AST and ALT <3 x ULN - or ≤5 x ULN if related to leukemic involvement) Kidney function (estimated creatinine clearance > 50 mL/min). Known cardiac ejection fraction of > or = 45% within the past 3 months

5. ECOG performance status of ≤ 2.

6. A negative urine pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial.

7. Patient must have the ability to understand the requirements of the study and signed informed consent. A signed informed consent by the patient or his legally authorized representative is required prior to their enrollment on the protocol.

The effects of APG1252 on the developing human fetus are unknown. For this reason and because BCL-2/BCL-XL inhibitors as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. (Refer to Pregnancy Assessment Policy MD Anderson Institutional Policy # CLN1114). This includes all female patients, between the onset of menses (as early as 8 years of age) and 55 years unless the patient presents with an applicable exclusionary factor which may be one of the following:

• Postmenopausal (no menses in greater than or equal to 12 consecutive months).
• History of hysterectomy or bilateral salpingo-oophorectomy.
• Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy).
• History of bilateral tubal ligation or another surgical sterilization procedure.

Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.

Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of APG1252 administration. Ability to understand and the willingness to sign a written informed consent document.