We found that patients with CLL cells harboring mutated XPO1 were diagnosed at a significantly younger median age, and more often presented with an advanced Rai stage than patients with CLL that expressed unmutated IgHV or had LP-CLL signatures but had wt XPO1. Patients with CLL cells that had mutated XPO1 also had higher absolute blood lymphocyte counts (WBC) at time of diagnosis than comparable patients with CLL cells that had wt XPO1. Here, XPO1 is linked to B-cell chronic lymphocytic leukemia.