Chronic lymphocytic leukemia with a FGFR3 translocation: Case report and literature review of an uncommon cytogenetic event

2014-09-20 00:02:34

Cancer Genetics; 19 SEPT 2014; DOI:10.1016/j.cancergen.2014.09.004

Matthew D. Geller, Ying Pei, Stephen E. Spurgeon, Connie Durum, Nicky J. Leeborg


The t(4;14)(p16; q32) with fusion of the IGH and FGFR3 genes (immunoglobulin heavy chain/fibroblast growth factor receptor 3) are rarely present in patients with chronic lymphocytic leukemia, with only two previously reported cases. Here we describe a unique case of chronic lymphocytic leukemia with the occurrence of t(4;14)(p16;q32), trisomy 12 and deletion of 11q13-q23 in the same clonal cells. In contrast to myeloma in which FGFR3 translocations are a common early cytogenetic hit, FGFR3 rearrangement in chronic lymphocytic leukemia appears to occur later in the disease course.


B-cell chronic lymphocytic leukemia (CLL) is the most common leukemia of adults in Western countries, occurring predominantly in the elderly. Clinical outcome is highly variable. Some patients follow an aggressive course, yet others have a more indolent disease and can be observed for many years, prior to needing CLL directed therapy. Prognosis depends largely on cytogenetic abnormalities and mutational status of the variable region of the immunoglobulin heavy chain gene (IgVH). Cytogenetic abnormalities can be detected in more than 80% of cases and are conventionally used to subclassify patients into 3 prognostically relevant subgroups. The favorable risk group includes those with deletion 13q14.3 as the sole abnormality. The intermediate group includes normal karyotype, trisomy 12, or 6q deletion and the unfavorable group includes 11q22/ATM deletion, deletion of 17p13/TP53, or complex karyotypes. The variety of chromosomal abnormalities described in CLL is constantly expanding and many prognostically relevant structural abnormalities, including balanced translocations, are currently under recognized. Discovery of these new genetic alterations may have the potential to further stratify prognostic groups and influence treatment.

Here, we report a unique case of CLL with coexistent t(4:14) (p16; q32), trisomy 12, and deletion of 11q. The acquisition of the t(4;14) paralleled a marked lymphocytosis to over 250 K/cu mm and a significant increase in the percentage of prolymphocytes, findings associated with poor outcome in CLL.

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Key Words

Chronic Lymphocytic Leukemia | cytogenetic translocation | FISH | prognosis