This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Faderl, S. Articles by Albitar, M. Search for Related Content PubMed PubMed Citation Articles by Faderl, S. Articles by Albitar, M.

The Prognostic Significance of p16^INK4a/p14^ARF and p15^INK4b Deletions in Adult Acute Lymphoblastic Leukemia

Departments of Leukemia [S. F., H. M. K., S. P., J. C., D. T., Z. E.] and Laboratory Medicine [T. M., C-Y. C., K. J. H., M. A.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

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.

This article has been cited by other articles:

				A. Vitale, A. Guarini, C. Ariola, M. Mancini, C. Mecucci, A. Cuneo, F. Pane, G. Saglio, G. Cimino, A. Tafuri, et al. Adult T-cell acute lymphoblastic leukemia: biologic profile at presentation and correlation with response to induction treatment in patients enrolled in the GIMEMA LAL 0496 protocol Blood, January 15, 2006; 107(2): 473 - 479. [Abstract] [Full Text] [PDF]

				M. Mancini, D. Scappaticci, G. Cimino, M. Nanni, V. Derme, L. Elia, A. Tafuri, M. Vignetti, A. Vitale, A. Cuneo, et al. A comprehensive genetic classification of adult acute lymphoblastic leukemia (ALL): analysis of the GIMEMA 0496 protocol Blood, May 1, 2005; 105(9): 3434 - 3441. [Abstract] [Full Text] [PDF]