This Article 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 Nakai, H. Articles by Ishizaki, K. Search for Related Content PubMed PubMed Citation Articles by Nakai, H. Articles by Ishizaki, K.

Frequent p53 Gene Mutations in Blast Crisis of Chronic Myelogenous Leukemia, Especially in Myeloid Crisis Harboring Loss of a Chromosome 17p¹

Third Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602, Japan [H. N., S. M.]; Department of Orthopedic Surgery, Faculty of Medicine [J. T.], and Radiation Biology Center [K. I.], Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606, Japan; Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts 02114 [D. W. Y.]

² To whom requests for reprints should be addressed.

We investigated chromosome alterations and mutations of the p53 gene in 118 samples from 92 patients with chronic myelogenous leukemia in various clinical phases, i.e., chronic phase, accelerated phase, and blast crisis (BC). Single-strand conformation polymorphism analysis and subsequent nucleotide sequencing disclosed no alteration of the p53 gene in chronic phase (no mutation in 80 samples), while five of 31 BC samples showed point mutations: four in myeloid and one in lymphoid crisis. One of seven accelerated phase samples also showed a p53 gene mutation. Ten of 31 BC samples showed loss of one of the short arms of chromosome 17 (17p) through the formation of isochromosome 17q, i(17q), or unbalanced translocations. Loss of heterozygosity at the p53 locus in the accelerated phase and BC was detected only in two cases with i(17q) but not in seven cases with normal chromosome 17 homologues, suggesting that loss of one p53 allele is rare without cytogenetically detectable loss of a 17p. Among those six samples with p53 gene mutations, five showed loss of a 17p cytogenetically, and only one lymphoid crisis case exhibited normal chromosome 17 homologues. Thus, mutations of the p53 gene were closely associated with myeloid crisis with loss of a 17p (four mutations in ten samples), in contrast to myeloid crisis with normal chromosome 17 homologues (zero in 13) or lymphoid crisis (one in seven). Our results also suggest that alterations of the p53 gene might occur after loss of a 17p during the course of chronic myelogenous leukemia.

¹ This work was supported in part by Grants-in-Aid from the Ministry of Education, Science, and Culture of Japan.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 6/26/92. Accepted 9/24/92.

This article has been cited by other articles:

				A. M. Gruszka-Westwood, R. A. Hamoudi, E. Matutes, E. Tuset, and D. Catovsky p53 abnormalities in splenic lymphoma with villous lymphocytes Blood, June 1, 2001; 97(11): 3552 - 3558. [Abstract] [Full Text] [PDF]

				K. M. Klucher, D. V. Lopez, and G. Q. Daley Secondary Mutation Maintains the Transformed State in BaF3 Cells With Inducible BCR/ABL Expression Blood, May 15, 1998; 91(10): 3927 - 3934. [Abstract] [Full Text] [PDF]

				D. G. Tenen, R. Hromas, J. D. Licht, and D.-E. Zhang Transcription Factors, Normal Myeloid Development, and Leukemia Blood, July 15, 1997; 90(2): 489 - 519. [Full Text] [PDF]

				M. J. Cline The Molecular Basis of Leukemia N. Engl. J. Med., February 3, 1994; 330(5): 328 - 336. [Full Text]