Activating Mutations of NOTCH1 in Human T Cell Acute Lymphoblastic Leukemia
AP Weng, AA Ferrando, W Lee, JP Morris IV… - Science, 2004 - science.org
AP Weng, AA Ferrando, W Lee, JP Morris IV, LB Silverman, C Sanchez-Irizarry, SC Blacklow…
Science, 2004•science.orgVery rare cases of human T cell acute lymphoblastic leukemia (T-ALL) harbor chromosomal
translocations that involve NOTCH1, a gene encoding a transmembrane receptor that
regulates normal T cell development. Here, we report that more than 50% of human T-ALLs,
including tumors from all major molecular oncogenic subtypes, have activating mutations
that involve the extracellular heterodimerization domain and/or the C-terminal PEST domain
of NOTCH1. These findings greatly expand the role of activated NOTCH1 in the molecular …
translocations that involve NOTCH1, a gene encoding a transmembrane receptor that
regulates normal T cell development. Here, we report that more than 50% of human T-ALLs,
including tumors from all major molecular oncogenic subtypes, have activating mutations
that involve the extracellular heterodimerization domain and/or the C-terminal PEST domain
of NOTCH1. These findings greatly expand the role of activated NOTCH1 in the molecular …
Very rare cases of human T cell acute lymphoblastic leukemia (T-ALL) harbor chromosomal translocations that involve NOTCH1, a gene encoding a transmembrane receptor that regulates normal T cell development. Here, we report that more than 50% of human T-ALLs, including tumors from all major molecular oncogenic subtypes, have activating mutations that involve the extracellular heterodimerization domain and/or the C-terminal PEST domain of NOTCH1. These findings greatly expand the role of activated NOTCH1 in the molecular pathogenesis of human T-ALL and provide a strong rationale for targeted therapies that interfere with NOTCH signaling.
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