The Pediatric Acute Leukemia (PedAL) Screening Trial - A Study to Test Bone Marrow and Blood in Children With Leukemia That Has Come Back After Treatment or Is Difficult to Treat - A Leukemia & Lymphoma Society and Children's Oncology Group Study

Inclusion Criteria:

* Patients must be less than 22 years of age at the time of study enrollment
* Patient must have one of the following at the time of study enrollment:

  * Patient has known or suspected relapsed/refractory (including primary refractory) AML as defined in protocol

    * This includes isolated myeloid sarcoma
  * Patient has known or suspected relapsed/refractory (including primary refractory) myeloid leukemia of Down syndrome (ML-DS)
  * Patient has known or suspected relapsed ALL as defined in protocol that meets one of the following criteria:

    * Second or greater B-ALL medullary relapse, excluding KMT2Ar
    * Any first or greater B-ALL medullary relapse involving KMT2Ar
    * Any first or greater T-ALL medullary relapse with or without KMT2Ar
  * Patient has known or suspected relapsed/refractory (including primary refractory) mixed phenotype acute leukemia (MPAL) as defined in protocol
  * Patient has known or suspected de novo or relapsed/refractory (including primary refractory) treatment-related AML (t-AML)
  * Patient has known or suspected de novo or relapsed/refractory (including primary refractory) myelodysplastic syndrome (MDS) or treatment-related myelodysplastic syndrome (t-MDS)

    * Note: Relapsed/refractory disease includes stable disease, progressive disease, and disease relapse.
  * Patient has known or suspected de novo or relapsed/refractory (including primary refractory) juvenile myelomonocytic leukemia (JMML)

    * Note: Relapsed/refractory disease includes stable disease, progressive disease, and disease relapse.
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met