Inclusion Criteria:  A histologically or pathologically confirmed diagnosis of AML based on WHO classification. Patients with myelodysplastic syndromes (MDS) or myeloproliferative neoplasms (MPN) evolving into AML who are candidates for AML induction therapy are eligible for enrollment. Age 18-65 years old. ECOG performance status < 3.  Patients must have normal organ function as defined below:  Total bilirubin ≤2X the institutional upper limit of normal (ULN) (except in patients with leukemic infiltration of the liver) AST(SGOT)/ALT(SGPT) ≤3X ULN (except if attributable to leukemic infiltration of the liver) Creatinine Clearance (CrCl) ≥ 40 mL/min (except in patients with evidence of tumor lysis syndrome) Left ventricular ejection fraction (LVEF) ≥50% Female patients of childbearing potential must have a negative pregnancy test <1 week before enrollment. Female patients of childbearing potential who are sexually active and male patients who are sexually active and have female partners of childbearing potential must agree to use a highly effective method of non-hormonal contraception. Contraception should be used during treatment and for at least 3 months after the last dose of Calaspargase pegol-mknl. Ability to understand and willingness to sign a written informed consent document. Agree to comply with the study requirements and agrees to come to the clinic/hospital for required study visits  Exclusion Criteria:  Patients with the following clinical histories are excluded:  severe pancreatitis not related to cholelithiasis. Severe acute pancreatitis as defined by lipase elevation >5X ULN and with signs or symptoms unprovoked DVT PE serious or life-threatening thrombosis in any location of the body hemorrhagic or thromboembolic stroke major hemorrhagic event within three weeks before signing ICF; hemorrhage due to thrombocytopenia from underlying AML is excluded patients with hemorrhagic diathesis neurologic/cerebellar disorders that may confound the toxicity monitoring of HiDAC history of serious hypersensitivity reactions to pegylated L-asparaginase therapy Patients receiving any other investigational agents or concurrent chemotherapy or immunotherapy. Hydroxyurea for blast count control is permitted before starting treatment and up to a maximum of 10 days after starting treatment on the study. Patients with AML with any of the following cytogenetic abnormalities: t(15;17), t(8;21), inv(16), t(16;16). Pregnant women and female patients who are lactating and do not agree to stop breast-feeding. Uncontrolled undercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled active seizure disorder, or psychiatric illness/social situations that per site Principal Investigator's judgment would limit compliance with study requirements