Analysis of CLLU1 expression levels before and after therapy in patients with Chronic Lymphocytic Leukemia

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BlankAnalysis of CLLU1 expression levels before and after therapy in patients

with Chronic Lymphocytic Leukemia.

AM Buhl, DF , D Neuberg, S Jain, LZ Rassenti, and TJ Kipps

Eur J Haematol, February 15, 2011;

Department of Hematology, Rigshospitalet, Copenhagen, Denmark Division of

Hematology/Oncology, Department of Medicine, University of California San Diego,

La Jolla, CA, USA, s UCSD Cancer Center, La Jolla, CA, USA The CLL Research

Consortium Department of Biostatics and Computational Biology, Dana-Farber

Cancer Institute, Boston, MA, USA Division of Biostatistics and Bioinformatics,

UCSD, La Jolla, CA., USA.

Objective: Chronic Lymphocytic Leukemia (CLL) is incurable, but therapy leading

to eradication of minimal residual disease (MRD) in CLL is associated with

improved clinical outcomes. CLL Upregulated gene 1 (CLLU1) is solely upregulated

in CLL patient samples. We hypothesized that CLLU1 could be used to monitor for

residual disease in CLL patient samples after therapy. Methods:? We examined if

the CLLU1 RQ-PCR could detect small numbers of CLL cells in mixtures of normal

peripheral blood mononuclear (PBMC) cells. We then performed a retrospective

analysis on time-matched cryo-preserved specimens from patients who achieved

MRD-negative remissions that underwent serial marrow biopsies for evaluation of

residual disease by 4-color flow cytometry. RNA from PBMC samples collected at

the time of the marrow was analyzed for CLLU1. Nine patients underwent a total

of 46-paired blood and marrow evaluations (median 5 assessments per patient).

Results: CLLU1 RQ-PCR on PBMCs of healthy donors reconstituted with varying

amounts of CLL cells demonstrated leukemia cells could be reliably detected with

high sensitivities depending on the CLLU1 expression level. Analysis of

time-matched samples assessed for CLLU1 levels in the blood by RQ-PCR and

residual disease of the marrow determined by 4-color flow cytometry revealed a

correlation coefficient of 0.96 (p<0.0001). Conclusion: The CLLU1 RQ-PCR is a

sensitive and specific assay for detecting residual CLL cells after therapy.

Assessment of blood CLLU1 levels can be used as a reliable marker of tumor

burden and has the potential to complement currently used techniques for MRD

monitoring in patients with CLL.

PMID: 21323738 .