Dealing with complexity: prognostic implications of karyotype and mutations in chronic lymphocytic leukemia

Over the last 40 years, much progress has been made in defining and understanding the genetic factors underlying the heterogeneity in the clinical course of patients with chronic lymphocytic leukemia (CLL). The presence of acquired clonal genetic abnormalities in CLL has been recognized since the early 1980s. However, correlation of chromosomal alterations with prognosis was hampered by the low mitotic rate of CLL cells, which results in only 40–50% of CLL samples having detectable chromosomal abnormalities using conventional karyotyping. Over the last 25 years, two technologic innovations, interphase FISH and stimulated karyotyping, have allowed investigation into the effect of these genetic changes on disease biology, prognosis, and response to therapy. Testing for the presence of known chromosome abnormalities with prognostic significance in CLL is now considered standard of care (1) and is most commonly done via employment of CLL FISH panels. However, the time consuming, technical nature of the culturing step has largely limited stimulated karyotype testing to referral centers.