Low CD49d expression and long telomere identify a chronic lymphocytic leukemia subset with highly favourable outcome

Abstract

CD49d expression and telomere length (TL) represent novel prognostic markers for chronic lymphocytic leukemia (CLL) [1―7]. The prognostic information carried by CD49d expression and TL in CLL has its rationale in the disease biology. CD49d is an adhesion molecule mediating cell-to-cell and cell-to-extracellular matrix interactions [8]. In CLL cells, CD49d transmits prosurvival/antlapoptotic signals from the tumor microenvironment to tumor cells [9]. Telomeres ensure genetic stability and regulate critical cellular functions, including proliferation and senescence [10]. In CLL, short TL associates with a fast proliferative history of the leukemic cells [1,11,12]. Both CD49d expression and short TL have been associated with increased genetic instability of the CLL clone [3,13]. From a clinical standpoint, a peculiar feature shared by CD49d expression and short TL is the association with CLL proliferation markers, including expression of CD38, high lactate dehydrogenase (LDH), high β-2-microglobulin, short time to lymphocyte doubling, and short time to progression to a more advanced stage [1―7]. Here, we tested whether the concomitant presence of high CD49d expression and short TL in the same CLL patient may help refine disease stratification for treatment prediction in patients that presented in early to intermediate Binet stage (Binet A and B) and that are candidate to watch and wait as initial management.