Inclusion Criteria:

* Patient has newly diagnosed acute leukemia:

* \> 25% blasts on a bone marrow (BM) aspirate or
* If a BM aspirate is not obtained or is not diagnostic of acute leukemia, the diagnosis can be established by a pathologic diagnosis of acute leukemia on a BM biopsy or
* A complete blood count (CBC) documenting the presence of at least 1,000/uL circulating leukemic blasts
* Adequate samples must be provided to the reference and/or COG-approved cytogenetics laboratories to allow completion of the studies needed for risk-stratification

* If a BM aspirate is not performed, or adequate material cannot be obtained, peripheral blood (PB) can be substituted for BM if there are at least 1,000 circulating blasts/uL (i.e., a white blood cell \[WBC\] count of 10,000/uL with 10% blasts or a WBC count of 5,000/uL with 20% blasts); if only PB is submitted, please obtain and send twice the volume of PB as the recommended BM volume specified; the patient will remain on AALL08B1 as long as all required central laboratory tests can be successfully performed; as long as there are at least 1,000/uL PB blasts, institutions are encouraged to submit PB in addition to BM samples to make sure that adequate material is available to perform the required studies
* If an adequate BM aspirate cannot be obtained and there are fewer than 1,000/uL PB blasts, the patient is not eligible for AALL08B1 or a frontline COG ALL clinical trial (there are NO exceptions to this rule)
* Patient has suspected ALL:

* Patients whose blast morphology is obviously myeloid, or whose blasts are myeloperoxidase positive, should not be enrolled on AALL08B1; however, patients with true biphenotypic or bilineage leukemia (i.e., patient presents with blasts with significant expression of multiple lymphoid and myeloid markers such that assignment to a single lineage is not possible) are eligible to enroll in AALL08B1 for cell banking
* Samples must be sent to a COG-approved cytogenetics laboratory, and COG Reference Laboratory studies; if informative results needed for treatment stratification are not available at specified time-points during induction, patients will not be eligible to receive post-induction therapy on a COG ALL trial
* 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

Exclusion Criteria:

* Patient must not have received prior cytotoxic therapy except for steroids or intrathecal chemotherapy
* Patient must not have secondary ALL that developed after treatment of a prior malignancy with cytotoxic chemotherapy