Study of Biomarkers in Blood and Bone Marrow Samples From Patients With Previously Untreated Chronic Lymphocytic Leukemia

• Relevance of common and uncommon interphase cytogenetic abnormalities related to baseline clinical features, complete response (CR), prolonged progression-free survival (PFS), and overall survival (OS) [ Designated as safety issue: No ]
• Significance of absence of IgVH gene mutational status as related to the ability to predict CR, PFS, and OS [ Designated as safety issue: No ]
• Correlation of IgVH gene mutational status with CD38 and ZAP-70 expression, over-expression of Mcl-1, BAK-1, high Mcl-1:Bax ratio, p53 mutation or dysfunction, high-risk karyotype abnormalities, other molecular features associated with poor outcome [ Designated as safety issue: No ]
• Prognostic significance of over-expression of Mcl-1, BAK-1, high Mcl-1:Bax ratio, p53 mutations or dysfunction, ATM mutation, ATM expression, and other factors that disrupt apoptosis with respect to CR, prolonged PFS, and OS [ Designated as safety issue: No ]
• Clonal evolution [ Designated as safety issue: No ]

RATIONALE: Studying samples of tumor tissue from patients with cancer in the laboratory may help doctors identify and learn more about biomarkers related to cancer.

PURPOSE: This research study is looking at biomarkers in blood and bone marrow samples from patients with previously untreated chronic lymphocytic leukemia.

OBJECTIVES:

• Determine the relevance of common and uncommon interphase cytogenetic abnormalities related to baseline clinical features, complete response (CR), prolonged progression-free survival (PFS), and overall survival (OS) in patients with previously untreated chronic lymphocytic leukemia.
• Determine the significance of the absence of IgV_H gene mutational status as related to the ability to predict CR, PFS, and OS in these patients.
• Correlate IgV_H gene mutational status with CD38 expression, ZAP-70 expression, over-expression of Mcl-1, BAK-1, high Mcl-1:Bax ratio, p53 mutations or dysfunction, high-risk karyotype abnormalities, and other molecular features associated with poor outcome in these patients.
• Determine the prognostic significance of over-expression of Mcl-1, BAK-1, high Mcl-1:Bax ratio, p53 mutations or dysfunction, ATM mutation, ATM expression, and other factors that disrupt apoptosis with respect to CR, prolonged PFS, and OS.
• Determine if clonal evolution occurs in these biological markers at partial response or disease relapse.

OUTLINE: This is a multicenter study.

Blood and bone marrow is collected at baseline, 3 months after completion of induction therapy, 2 months after completion of consolidation therapy, 1 year after completion of study treatment, and at disease relapse. Samples are analyzed by FISH for interphase cytogenetics, PCR for IgV_H mutational status, flow cytometry for surface expression of CD38 cells, western blot to assess Mcl-1, Bcl-2, BAK-1, ATM, ZAP-70, and Bar expression, and sequencing for p53 and ATM function.

• Genetic: fluorescence in situ hybridization
• Genetic: mutation analysis
• Genetic: nucleic acid sequencing
• Genetic: polymerase chain reaction
• Genetic: western blotting
• Other: flow cytometry
• Other: laboratory biomarker analysis

DISEASE CHARACTERISTICS:

• Diagnosis of chronic lymphocytic leukemia

  • Previously untreated disease
• Registered to receive treatment on a Cancer and Leukemia Group B protocol

PATIENT CHARACTERISTICS:

• Not specified

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics