Expression of Notch Pathway Proteins in Lymphoblastic Leukemia/Lymphoma
W Chen, P Kapur, T Isaacson, D Rakheja. UT Southwestern Medical Center, Dallas, TX
Background: The Notch proteins are a family of transmembrane receptors consisting of Notch1, Notch2, Notch3, and Notch4. Binding of a Notch protein to its cognate ligand (Jagged1) leads to its regululated proteolysis by γ-secretase, releasing the Notch intracellular domain (NICD). The NICD translocates to the nucleus and joins a transcriptional activation complex, stimulating the expression of a number of key genes involved in cell growth and proliferation. While activating mutations in Notch1 are found in 50-60% of T-lymphoblastic leukemia/lymphoma (LBL), expression of the Notch proteins and Jagged1 has not yet been well characterized in both T- and B-LBL and was the focus of this study.
Design: Immunohistochemical analysis (IHC) was performed using antibodies against Notch1 (Chemicon), Notch2 (Abcam), Notch3 (Abcam), Notch4 (Santa Cruz), and Jagged1 (Abcam) on sections of a tissue microarray consisting of 28 cases of pediatric LBL (24 of B- and 4 of T-LBL, respectively). Staining was evaluated on a scale of 0 (negative) to 3 (intensely positive in most cells), and the pattern of immunoreactivity was appraised.
Results: Strong expressions of Notch2 and Jagged1 with nuclear immunoreactivty (NI) were identified in 92 and 86% of cases, respectively. Expression of Notch1 was variable and relatively weak compared to Notch2, although 74% of the positive cases had NI pattern. Notch 3 expression was weaker and in a smaller number of cases, and none of cases had NI pattern but showed cytoplasmic staining. Notch4 was not expressed. There was no difference in expression between T- and B-LBL.