Blood Journal
Leading the way in experimental and clinical research in hematology

NOTCH1 mutations in CLL associated with trisomy 12

  1. Veronica Balatti1,*,
  2. Arianna Bottoni1,*,
  3. Alexey Palamarchuk1,
  4. Hansjuerg Alder1,
  5. Laura Z. Rassenti2,
  6. Thomas J. Kipps2,
  7. Yuri Pekarsky1, and
  8. Carlo M. Croce1
  1. 1Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH; and
  2. 2Department of Medicine, University of California at San Diego, La Jolla, CA


Two recent studies reported wholegenome sequencing of chronic lymphocytic leukemia (CLL) samples and found repeated mutations in the XPO1 and NOTCH1 genes. XPO1 was found mutated in 2.4% of cases, while NOTCH1 was found mutated in 12.2% or 15.1% of CLL samples. Here we report the results of sequencing of XPO1 and NOTCH1 in 186 CLL cases. Our results confirmed frequency of XPO1 mutations. However, we found only 5 NOTCH1 mutations in 127 IGVH unmutated/ZAP70+ CLL samples (4%), and one mutation was found in IGVH mutated/ZAP70 CLL for a total percentage of 1.5%. Because 4 of 6 mutated samples also showed trisomy 12, we sequenced NOTCH1 in an additional 77 cases with trisomy 12 CLLs, including 47 IGVH unmutated/ZAP70+ cases. Importantly, we found 41.9% NOTCH1 mutation frequency in aggressive trisomy 12 CLL cases. Our data suggest that activation of NOTCH1 plays a critical role in IGVH unmutated/ZAP70+ trisomy 12 CLL.

  • Submitted October 18, 2011.
  • Accepted November 13, 2011.
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