[1415] Single Nucleotide Polymorphism (SNP) Array Genomic Profiling Identified High Prevalence of Clonal Diversity Associated with Clinical Progress in Chronic Lymphocytic Leukemia.

Linsheng Zhang, Iya Znoyko, Sally E Self, Daynna J Wolff. Medical University of South Carolina, Charleston

Background: Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease; genomic aberrations are important prognostic factors. Acquisition of genetic mutations or clonal evolution, as shown by interphase fluorescent in situ hybridization (FISH), has been associated with disease progression. SNP microarray genomic profiling allows for interrogation of the entire genome at a high resolution to determine the amount of clonal heterogeneity in CLL.
Design: Whole genome analysis was performed in 14 CLL cases using the Illumina® HumanOmni1-Quad BeadChip SNP-array (Illumina, Inc. San Diego, California, USA). To identify clonal diversity, the percentage of cells in each clone was estimated from LogR and B-allele frequency data based on the SiDCon tool (Nancarrow, et. al. PLoS One. 2007; e1093). Concurrent FISH was also performed for each case. Clinical information, flow cytometry and conventional cytogenetics were reviewed from medical records. All studies were performed with institutional review board approval.
Results: Ten of the 14 cases had clonal diversity (more than one subclone as defined by percentage of cells containing specific genomic aberration). Cases with multiple clones were associated with late clinical stage, refractoriness to immunochemotherapy and disease progression (see table).

Clonal Diversity and Clinical Status
Case #SubclonesClinical StageClinical Status
1NoIAsymptomatic; WBC stable
2NoIAsymptomatic; WBC stable
3NoIVWBC stable; complicated hemolytic anemia and immune thrombocytopenia
4NoIIAsymptomatic; WBC stable
5YesIAsymptomatic; WBC slowly increasing
6YesIIAt stage IV in 2007; WBC and platelet fluctuate over the years
7YesIWBC doubled twice in 4 months, progressed to stage III and platelet decreasing
8YesIVIn clinical trial
9YesIVRelapsed, refractory to immunochemotherapy, recevied stem cell transplantation
10YesIVInitial diagnosis
11YesIVRefractory, transformed to prolymphocytic leukemia
12YesIVRelapsed after chemotherapy
13YesIIITP53 clonal expansion; progress from stage I to III in less than 2 years
14YesIVRelapsed and refractory; WBC doubled in 2 months
WBC: white celll count

Conclusions: Clonal heterogeneity is present in high percentage of CLL cases, and may be associated with clinical progression. Whole genome SNP array analysis is an excellent tool for the study of genetic diversity/clonal evolution, and can be used to independently establish prognosis of patients with CLL.
Category: Hematopathology

Monday, February 28, 2011 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 188, Monday Morning


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