Study of 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.

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

Primary outcomes

• complete response [Up to 10 years]
• prolonged progression-free survival [Up to 10 years]
• overall survival [Up to 10 years]

Sex: All

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

• John C. Byrd, MD, Study chair, Ohio State University Comprehensive Cancer Center