Inclusion Criteria:

• Understand and voluntarily sign an informed consent form participants ≥18 years, unless parent or LAR signs along with any required verbal assents and signed assent of minor for participants <18 years.
• Age ≥18 years at the time of signing the informed consent form.
• Age ≥1 years and <18 years with weight requirement ≥8 kg at the time of the signing of the informed consent form (e.g. by parent or LAR)
• Patients enrolling in the pediatric/adolescent/young adult exploratory cohort must be:

Age ≥1 years and <18 years with weight requirement ≥8 kg at the time of the signing of the informed consent form (e.g. by parent or LAR), Or age 18 years -39 years at the time of the signing of the informed consent form

• Diagnosis of any of the following:
• Newly diagnosed (or untreated) AML with intermediate-risk/poor-risk cytogenetics, intermediate-risk/poor-risk molecular, or secondary AML (i.e. therapy-related or evolved from antecedent hematologic malignancy)
• Newly diagnosed (or untreated) myeloid blast phase of myeloproliferative neoplasm (MPN) (including myeloid blast phase of chronic myeloid leukemia [CML])
• Newly diagnosed (or untreated) high-risk, very-high risk or secondary MDS/myeloid neoplasm
• Newly diagnosed (or untreated) MDS/MPN (regardless of cytogenetic/molecular status)
• Relapsed and/or refractory AML, MDS/myeloid neoplasm , MDS/MPN, myeloid blast phase of MPN (including myeloid blast phase of CML)
• Patients enrolling in the childhood/adolescent/young adult exploratory cohort may have any of the following diagnoses:
• High-risk or relapsed/refractory childhood, adolescent, or young adult malignancies including but not limited to high-risk or relapsed/refractory ALL or other high-risk or relapsed refractory malignancies
• This includes, but is not limited to, the following: High-risk ALL/LL including T-ALL/LL, Ph-like ALL/LL, Ph+ B-ALL/LL, B-ALL/LL with CNS lymphoid leukemic involvement, testicular involvement, other extramedullary involvement by ALL/LL; ALL/LL with any of the NCI high-risk features: patients aged 10 years or older and those with a white blood cell count ≥50 × 109 per L), high-risk cytogenetics (MLL rearrangements, near haploidy [<30 chromosomes], low hypodiploidy [30-39 chromosomes], t[17;19][q23;p13], intrachromosomal amplification of chromosome 21), Burkitts'; Burkitt's-like, Double-Hitt; CNS involvement by any non-primary brain malignancy; Metastatic disease of any malignancy; 5-year survival prognosis of less than 50%, based on the treating physician's assessment
• Patients on non-investigational regimens or on IND-exempt MD Anderson studies (for hematologic malignancies) of approved drugs are also eligible.
• Patients on IND studies (for hematologic malignancies) utilizing FDA approved commercially available drugs are eligible.
• Investigational agents that are not used for treatment of the leukemia per se (e.g. anti-infective prophylaxis or therapy) will be allowed. Other supportive care studies are allowed, even if under an IND.
• Newly diagnosed MDS or AML, as well as MDS/MPN, myeloid blast phase of MPN (including myeloid blast phase of CML), patients can enroll on this study after start of non-investigational induction therapy, but must be within first 3 cycles of therapy of front-line therapy. Patients with relapsed and/or refractory AML, MDS, MDS/MPN, myeloid blast phase of MPN (including myeloid blast phase of CML) can enroll. Newly diagnosed patients enrolling in the exploratory cohort with high-risk malignancies can enroll after the start of non-investigational therapy but must be within first 3 cycles of front-line therapy.
• Transformed and untreated AML transformed from previously treated MDS, myeloproliferative neoplasm (MPN) or other types of secondary AML are allowed. Myeloid-Blast Phase of MPN and Chronic Myeloid Leukemia (CML) are allowed.
• Eastern Cooperative Oncology Group (ECOG) performance status of =< 3 or Lansky or Karnofsky ≥ 30 at study entry; patients who are unable to walk, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• Laboratory test results within these ranges (unless due to leukemia or other hematologic malignancy):
• Serum creatinine =< 1.5 mg/dL
• Total Bilirubin =< 2.0 x upper limit of normal (ULN), unless the patient has Gilbert's
• AST (SGOT) and/or ALT (SGPT) =< 2.0 x ULN
• Women of childbearing potential (WCBP) must have a negative urine pregnancy test within 7 days and must either commit to continued abstinence from heterosexual intercourse or adopting at least one highly effective method of contraception. These methods include intra-uterine device, tubal ligation, partner's vasectomy, and hormonal birth control pills. Men must agree not to father a child and agree to use a condom if his partner is of child bearing potential
• Extramedullary disease is allowed as long as it can be measured and followed for response.

Note: Patients can be considered MDS by either WHO or FAB150 criteria Note: MDS risk status assessment is based on IPSS-R and/or IPSS-M. AML risk status assessment is based on ELN and World Health Organization classification

Exclusion Criteria:

• Nursing and pregnant females. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Uncontrolled inter-current illness including, but not limited to, uncontrolled active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements or which judged by the investigator, places the patient at unacceptable risk
• Acute Promyelocytic leukemia (APL)