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CDKN2A/B alterations impair prognosis in adult BCR-ABL1-positive acute lymphoblastic leukemia patients

Ilaria Iacobucci1, Anna Ferrari, Annalisa Lonetti

  • 1Department of Hematology and Oncological Sciences "L. and A. Seràgnoli" S.Orsola Malpighi Hospital, University of Bologna, Italy.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|December 3, 2011
PubMed
Abstract

Insights

Genomic deletions at the 9p21 locus are common in BCR-ABL1-positive acute lymphoblastic leukemia (ALL). These alterations, particularly CDKN2A/B deletions, indicate a poor prognosis and may arise during disease progression.

Area of Science:

  • Genetics
  • Oncology
  • Molecular Biology

Background:

  • The 9p21 locus contains critical tumor suppressor genes (p16/CDKN2A, p14/ARF, p15/CDKN2B).
  • Inactivation of this locus is implicated in the development of various human cancers.

Purpose of the Study:

  • To investigate the frequency, size, and prognostic significance of alterations at the 9p21 locus in adult BCR-ABL1-positive acute lymphoblastic leukemia (ALL).
  • To analyze genomic changes at diagnosis and relapse in ALL patients.

Main Methods:

  • Genome-wide single-nucleotide polymorphism arrays and deep exon sequencing were employed.
  • Analysis included 112 patients with BCR-ABL1-positive ALL (101 de novo, 11 relapsed).
  • Paired diagnosis-relapse samples were analyzed for 19 patients.

Main Results:

  • Genomic alterations at 9p21 (CDKN2A/ARF, CDKN2B) were found in 29% and 25% of newly diagnosed patients, respectively.
  • Deletions were predominantly monoallelic (72%), with a significant subset affecting only the CDKN2A/B locus (43%).
  • Loss of CDKN2A/ARF increased at relapse (47%) compared to diagnosis. Deletions of CDKN2A/B correlated with worse overall survival, disease-free survival, and increased relapse incidence.

Conclusions:

  • Genomic deletion at the 9p21 locus is a frequent event in BCR-ABL1-positive ALL.
  • These deletions are often acquired during leukemia progression.
  • 9p21 deletions serve as a significant negative prognostic marker for long-term outcomes in ALL.

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