SOHO 2021 | Utilizing the NOTCH1 pathway in the treatment of CLL
Silvia Deaglio, MD, PhD, of the University of Turin, Turin, Italy, discusses the significance of the NOTCH1 pathway in the treatment of chronic lymphocytic leukemia (CLL). NOTCH1 is the most commonly mutated gene in CLL, present in approximately 10-12% of patients with CLL. Among those resistant to treatment, one in three patients are found to bear this mutation, highlighting the significance of the NOTCH1 pathway for disease progression. NOTCH1 currently cannot be targeted, though can be used as a marker. This interview took place during the ninth annual meeting of the Society of Hematologic Oncology (SOHO 2021) congress.
Transcript (edited for clarity)
The NOTCH1 pathway in CLL is an emerging oncogenic pathway. NOTCH1 is the single most common mutation in CLL, and we have about 10% to 12% patients are diagnoses who bear a mutation that’s largely impacting on the structure of the NOTCH1 molecule by bearing a 2-nucleotide deletion in exon 34, that’s the PEST domain deletion in molecular terms. This percentage of mutation significantly increases when we are looking at patients that become resistant to therapies, or when we are looking at patients that are progressing, so that you have about 1 in 3 that bear this mutation...
The NOTCH1 pathway in CLL is an emerging oncogenic pathway. NOTCH1 is the single most common mutation in CLL, and we have about 10% to 12% patients are diagnoses who bear a mutation that’s largely impacting on the structure of the NOTCH1 molecule by bearing a 2-nucleotide deletion in exon 34, that’s the PEST domain deletion in molecular terms. This percentage of mutation significantly increases when we are looking at patients that become resistant to therapies, or when we are looking at patients that are progressing, so that you have about 1 in 3 that bear this mutation. This is an indirect indication that it has a negative value, that in fact, cells that bear these mutations are more resistant, are more aggressive, and eventually take over the unmutated population.
Can we target to NOTCH1? Not really and not so much right now. We can use it, again, as I said, as a marker. And so it is important to know before treating a patient, the mutational status in order to refine prognosis. And we know that patients that bear a NOTCH1 mutation will probably signal more through the BCR, and so they would probably benefit from BCR-signaling inhibitors.
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Disclosures
Silvia Deaglio, MD, PhD, has a sponsored research agreement with Heidelberg Pharma, and Astra Zeneca.
