Using primary CLL cells classified as NOTCH1 wild-type (CLL/N<sup>WT</sup>) or mutated (CLL/N<sup>M</sup>), both with UM-BCR, we show that BCR stimulation activates the NOTCH1 pathway, upregulating metabolic programs and mitochondrial biogenesis, selectively in CLL/N<sup>M</sup>. Here, NOTCH1 is linked to B-cell chronic lymphocytic leukemia.