Considering that NOTCH2 is a tumor-inducing oncogene [10] and indispensable for CLL development in a mouse model [12], we hypothesize that the induction of a NOTCH2ΔNRR GOF phenotype by somatic recombination has the potential to be an initial malignant hit in a CLL precursor cell. Here, NOTCH2 is linked to B-cell chronic lymphocytic leukemia.