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Notch-1 mutations are secondary events in some patients with T-cell acute lymphoblastic leukemia.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Mansour, Marc R. Duke, Veronique M. Foroni, Letizia Patel, Bella Allen, Christopher Ancliff, Philip James Gale, Rosemary E. Linch, David Christopher |
| Copyright Year | 2007 |
| Abstract | PURPOSE Activating Notch-1 mutations are frequent in T-cell acute lymphoblastic leukemia (T-ALL), occurring in >50% of patients. In murine models of T-ALL, Notch-1 activation can both directly initiate leukemia and cooperate secondarily to other primary events. Whether acquisition of Notch-1 mutations is an early initiating event or a secondary event in the pathogenesis of human T-ALL is unclear. EXPERIMENTAL DESIGN We used denaturing high-performance liquid chromatography, sequencing, and fragment analysis to analyze Notch-1 mutational status and mutant level in 62 patients at presentation as well as 16 matched presentation-relapse samples. RESULTS We detected Notch-1 mutations in 47 patients (76%). Seven of these were low-level mutations (quantified at < or =10%), despite high blast counts, suggesting that they were acquired as a secondary event in a subclone. Of 16 matched presentation-relapse samples studied, 7 were wild-type at both presentation and relapse. Five of nine mutant-positive patients at presentation relapsed with the same mutation(s) at the same high level. Four patients had evidence of a change in mutant at relapse. One lost a PEST mutation and became wild-type. Two others lost mutations at relapse but acquired different mutations, despite unchanged T-cell receptor rearrangements, suggesting that the latter event predated the acquisition of the Notch-1 mutation. One relapsed with a secondary T-cell leukemia and different Notch mutation. CONCLUSIONS These results suggest that Notch-1 mutations can sometimes be acquired as secondary events in leukemogenesis and must be used cautiously as solitary minimal residual disease markers. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://clincancerres.aacrjournals.org/content/clincanres/13/23/6964.full.pdf |
| PubMed reference number | 18056171v1 |
| Volume Number | 13 |
| Issue Number | 23 |
| Journal | Clinical cancer research : an official journal of the American Association for Cancer Research |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Adult T-Cell Lymphoma/Leukemia Biopolymer Sequencing Chronic Lymphocytic Leukemia DNA Sequence Rearrangement Leukemia, B-Cell Leukemogenesis Liquid Chromatography Mutation Neoplasm, Residual Patients Precursor Cell Lymphoblastic Leukemia Lymphoma Precursor T-Cell Lymphoblastic Leukemia-Lymphoma T-Lymphocyte lymphoblast |
| Content Type | Text |
| Resource Type | Article |
