Trial Information

Assessment of Novel Molecular Markers in Acute Myeloid Leukemia

OBJECTIVES:

- Prospectively obtain specimens required for diagnostic review and molecular
characterization ensuring eligibility for CALGB Leukemia Committee Clinical trials (for
clinical trials designed to enroll specific molecular subtypes, results to determine
eligibility will be reported to treating physicians no more than 72 hours after
specimen receipt at the repository).

- Determine the frequency of specific gene markers (i.e., FLT3 ITD, CBF, MLL PTD, NPM1,
KIT, RAS, CEBPA, WT1, JAK2, RUNX1, TET2, CBL, IDH1 and IDH2, ASXL1, mutations, aberrant
BAALC, ERG, FLT3, MN1, EVI1, and APP) over-expression and levels of promoter
methylation of specific genes (e.g., ESR1, WIT1, P15, MYOD1, ID4, DPK) in defined
cytogenetic subgroups of patients with acute myeloid leukemia (AML).

- Correlate these gene markers with clinical and laboratory parameters in these patients.

- Correlate these gene markers with clinical outcome (i.e., complete remission [CR],
disease-free survival [DFS], cumulative incidence of relapse [CIR], and overall
survival [OS]) in these patients.

- Identify specific microarray multi-gene expression signatures in these patients.

- Correlate specific microarray multi-gene expression signatures with clinical and
laboratory parameters in these patients.

- Correlate specific microarray multi-gene expression signatures with clinical outcome
(i.e., CR, DFS, CIR, and OS) in these patients.

- Identify specific microarray multi-microRNA (miR) expression signatures in these
patients

- Correlate specific microarray multi-miR expression signatures with clinical and
laboratory parameters in these patients.

- Correlate specific microarray multi-miR expression signatures with clinical outcome
(i.e., CR, DFS, CIR, and OS) in these patients.

- Explore the relative contribution of prognostic gene markers (i.e., FLT3 ITD, MLL PTD,
NPM1, KIT, RAS, CEBPA, WT1, and JAK2 mutations, and aberrant BAALC, ERG, FLT3, MN1, and
EVI1 over-expression), levels of promoter methylation of specific genes (e.g., ESR1,
WIT1, P15, MYOD1, ID4, DPK), and microarray gene and miR expression signatures in
defined cytogenetic subgroups of AML.

- Determine changes in these molecular markers and microarray gene and miR expression
signatures at CR and relapse and the influence that these changes have on subsequent
clinical course.

- Correlate the relative level of nuclear pSTAT5 and pERK in bone marrow blasts with
outcome (EFS, CR, DFS, OS).

OUTLINE: This is a multicenter study.

Previously procured and archived bone marrow aspirate samples, blood and buccal cell
samples, and bone marrow biopsy slides are analyzed for FLT3 ITD, MLL PTD, NPM1, KIT, KRAS,
NRAS, CEBPA, WT1, JAK2, RUNX1, TET2, ASXL1, IDH1 and IDH2, and CBL mutations, CBF fusion
genes, levels of BAALC, ERG, EVI1, MN1, and APP microarray gene-expression, microRNA
gene-expression signature, levels of methylation of genes silenced in AML, and genomic DNA
by PCR amplification, RT-PCR, and denaturing high-performance liquid chromatography.