HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

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

Decreased or Altered Expression of the FHIT Gene in Human Leukemias

Department of Hematology, Juntendo University School of Medicine and the Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Tokyo, Japan

Key Words. Ap4A asymmetrical hydrolase • Exon skipping • FHIT gene • Inducible fragile site • Leukemia • RT-PCR • Tumor suppressor gene

Dr. Koichi Sugimoto, Department of Hematology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113, Japan.

The FHIT (fragile histidine triad) gene on chromosome 3p14 is a candidate tumor suppressor gene, and its transcripts are shown to be abnormal in several human cancers. We examined 40 leukemia samples for the alterations of FHIT transcripts by reverse transcriptase-polymerase chain reaction (RT-PCR) and direct sequencing. Intact FHIT mRNA was not detected in two patients with acute myeloid leukemia (AML) and in one patient with chronic lymphocytic leukemia (CLL). The three cases expressed only an aberrant FHIT mRNA lacking exons 3 to 6 (FHIT 3-6 mRNA), which could encode a polypeptide of 13 amino acids. Southern blot analysis on two samples from these cases showed no rearrangements of the FHIT gene. Although intact FHIT mRNA was detected as the main band in the remaining 37 samples, 33 of them (14 of 14 AML, 11 of 13 chronic myeloid leukemia, five of five acute lymphocytic leukemia, and three of five CLL) expressed aberrant FHIT 3-6 mRNA. We barely detected the FHIT 3-6 mRNA in only one of 25 normal control samples. Our results suggest that loss of the normal FHIT function may be involved in the genesis of at least some human leukemias and that expression of aberrant FHIT transcripts is rather specific and frequent in leukemia samples.

This article has been cited by other articles:

				F. Pichiorri, F. Trapasso, T. Palumbo, R. I. Aqeilan, A. Drusco, B. W. Blaser, D. Iliopoulos, M. A. Caligiuri, K. Huebner, and C. M. Croce Preclinical Assessment of FHIT Gene Replacement Therapy in Human Leukemia Using a Chimeric Adenovirus, Ad5/F35. Clin. Cancer Res., June 1, 2006; 12(11): 3494 - 3501. [Abstract] [Full Text] [PDF]

				E. F. Srour, X. Tong, K. W. Sung, P. A. Plett, S. Rice, J. Daggy, C. T. Yiannoutsos, R. Abonour, and C. M. Orschell Modulation of in vitro proliferation kinetics and primitive hematopoietic potential of individual human CD34+CD38-/lo cells in G0 Blood, April 15, 2005; 105(8): 3109 - 3116. [Abstract] [Full Text] [PDF]

				L. Gallacher, B. Murdoch, D. Wu, F. Karanu, F. Fellows, and M. Bhatia Identification of novel circulating human embryonic blood stem cells Blood, September 1, 2000; 96(5): 1740 - 1747. [Abstract] [Full Text] [PDF]

				H. M. Kantarjian, M. Talpaz, S. O'Brien, T. Manshouri, J. Cortes, F. Giles, M. B. Rios, C. M. Croce, and M. Albitar Significance of FHIT Expression in Chronic Myelogenous Leukemia Clin. Cancer Res., December 1, 1999; 5(12): 4059 - 4064. [Abstract] [Full Text] [PDF]

				C. Hallas, M. Albitar, J. Letofsky, M. J. Keating, K. Huebner, and C. M. Croce Loss of FHIT Expression in Acute Lymphoblastic Leukemia Clin. Cancer Res., September 1, 1999; 5(9): 2409 - 2414. [Abstract] [Full Text] [PDF]