Cryptic Unbalanced Chromosomal Changes in a Case of Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma (CLL/SLL) Identified By Single Nucleotide Polymorphism (SNP) Microarray, but Not By Conventional Karyotyping

Genomic abnormalities have been widely used to diagnose and provide prognostic significance in many hematologic malignancies (HM). The use of conventional G-banded chromosome and fluorescence in situ hybridization (FISH) analyses sometimes fail to detect genomic abnormalities due to the need for actively dividing cells and lower resolution of chromosome analysis (G-banded), as well as the inability to detect copy number of neutral loss of heterozygocity (G-banded and FISH). The addition of single nucleotide polymorphism (SNP) microarray has been shown to increase the detection rate of genomic abnormalities in HM.

We report a 62-year-old Caucasian woman with a diagnosis of chronic lymphocytic leukemia /small lymphocytic lymphoma (CLL/SLL). Cytogenetic studies done at the time when she required initial treatment in 2011 showed a balanced translocation between chromosomes 6 and 13 {46,XX,t(6;13)(p10;q10)[10]/46,XX[10]}. She was treated with bendamustine plus rituximab and achieved complete response. In 2013, she developed worsening of anemia and marked lymphocytosis. Blood and bone marrow examination showed polymphocytic transformation. G-banded cytogenetic studies again showed a balanced translocation between chromosomes 6 and 13 (same as in 2011). However, FISH analysis detected a deletion of 13q. G-banded cytogenetic study was re-examined and showed balanced translocation: 46,XX,t(6;13)(p10;q10)[10]/46,XX[10]. Re-analysis of bone marrow cytogenetic from 2011 also suggested possible deletion of 13q, but the resolution was poor. Cytogenetic microarray validation was performed and revealed not only deletions of 13q14.2q14.3, but also 6p21.1p21.1. Karyotypic changes of chromosome 6 have been associated with prolymphocytic transformation in CLL/SLL.

Deletion of 13q14.3 usually carries good prognosis in CLL/SLL. However, additional abnormalities and deletions of different sizes of 13q reportedly cooperate to change its favorable value. An accurate cytogenetic analysis may be useful in aiding in diagnosis, prognosis, and possibly therapy. Our findings suggest that microarray analysis is a suitable companion test to G-banded chromosome and FISH analyses, especially in CLL/SLL.