NOTCH1 and acute lymphoblastic leukemia: Less macroscopic mutations, although directly activating, were then found in the extracellular heterodimerization domain (HD) and/or the C-terminal PEST intracellular domain of the Notch 1 gene [43] and in the extracellular juxtamembrane region [44] in about 60% and 30% of T-ALL cases, respectively.