The prognostic significance of p16(INK4a)/p14(ARF) and p15(INK4b) deletions in adult acute lymphoblastic leukemia

Stefan Faderl, Hagop M. Kantarjian, Taghi Manshouri, Chin Yung Chan, Sherry Pierce, Kimberly J. Hays, Jorge Cortes, Deborah Thomas, Zeev Estrov, Maher Albitar

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Cytogenetic/molecular abnormalities significantly influence the prognosis of patients with acute leukemia. Recently, two genes, p16(INK4a) and p15(INK4b), encoding two cyclin-dependent kinase inhibitor proteins of the INK4 family of M(r) 15,000 and 16,000, respectively, have been localized to 9p21. Remarkably, the p16(INK4a) locus has been found to encode a second protein, p14(ARF), known as p19(ARF) in mice, with a distinct reading frame. Like p16(INK4a), p14(ARF) is involved in cell cycle regulation, blocking cells at the G1 restriction point through the activity of MDM-2 and p53. We studied bone marrow samples of 42 newly diagnosed and untreated patients with acute lymphoblastic leukemia for the incidence of deletions of p16(INK4a/p14(ARF) and p15(INK4b) using Southern blot analysis and determined the clinical outcome with regard to complete remission (CR) duration, event- free survival, and overall survival. We found deletions of p16(INK4a)/p14(ARF) in 17 of 42 patients (40%), with homozygous deletions in 11 of 42 patients (26%) and hemizygous deletions in 6 of 42 patients (14%). The gene for p15(INK4b) was codeleted in most, but not all, cases and was never deleted without deletion of p16(INK4a)/p14(ARF). NO correlation was observed between molecular studies and karyotype abnormalities as determined by conventional cytogenetics. Furthermore, no difference was found in the CR rate, CR duration, event-free survival, and overall survival in patients with homozygous gene deletions compared to patients with no deletions or loss of only one allele.

Original languageEnglish (US)
Pages (from-to)1855-1861
Number of pages7
JournalClinical Cancer Research
Volume5
Issue number7
StatePublished - Jul 1 1999
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Faderl, S., Kantarjian, H. M., Manshouri, T., Chan, C. Y., Pierce, S., Hays, K. J., Cortes, J., Thomas, D., Estrov, Z., & Albitar, M. (1999). The prognostic significance of p16(INK4a)/p14(ARF) and p15(INK4b) deletions in adult acute lymphoblastic leukemia. Clinical Cancer Research, 5(7), 1855-1861.