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 Rogaia, D. Articles by Pelicci, P. G. Search for Related Content PubMed PubMed Citation Articles by Rogaia, D. Articles by Pelicci, P. G.

The Localization of the HRX/ALL1 Protein to Specific Nuclear Subdomains Is Altered by Fusion with Its eps15 Translocation Partner¹

European Institute of Oncology, Department of Experimental Oncology, 20141 Milan, Italy [D. R., R. C., P. P. D., P. G. P.]; Istituto di Medicina Interna e Scienze Oncologiche, Perugia University, 06100 Perugia, Italy [D. R., F. G., P. G. P.]; Dipartimento di Ematologia, Università La Sapienza, 00161 Rome, Italy [F. L. C.]; Istituto di Microbiologia, University of Bari, Italy [P. P. D.]; and Thomas Jefferson University, Philadelphia, Pennsylvania 19107-5541 [C. M. C., T. N.]

Translocations involving the HRX/ALL1 locus at chromosomal region 11q23 are among the most frequent cytogenetic abnormalities in acute leukemias. 11q23 translocations involve different chromosome partners and lead to the formation of HRX/ALL1 fusion proteins. The HRX/ALL1 protein is a putative transcription factor that has been implicated in developmental regulation in mammals. We report here the cellular localization of the HRX/ALL1 protein as well as that of the HRX/ALL1-eps15 fusion protein, the result of the t(1;11) (p32-q23) translocation of acute myeloid leukemias. The HRX/ALL1 protein was localized to both the cytoplasm and the nucleus. The nuclear pattern was characterized by diffuse staining, perinuclear accumulation, and localization within nuclear bodies of variable size, morphology, and number. The HRX/ALL1-eps15 localized exclusively to the nucleus within bodies that were smaller and more numerous than the HRX/ALL1 nuclear bodies. HRX/ALL1 fusion with an unknown partner in leukemia blasts with 11q23 abnormalities had similar morphological features. Thus, the fusion with eps15 alters the cellular compartmentalization of HRX/ALL1, providing a putative mechanism for activation of HRX/ALL1 by 11q23 abnormalities.

¹ Supported by European Community (Biomed and Biotech) and Associazione Italiana per la Ricerca sul Cancro.

² To whom requests for reprints should be addressed, at European Institute of Oncology, Department of Experimental Oncology, Via Ripamonti 435, 20141 Milan, Italy. Phone, 39-2-574-89-831; Fax, 39-2-574-89-851; E-mail: pgpelicci@ieo.cilea.it.

Received 12/26/96. Accepted 1/17/97.

This article has been cited by other articles:

				C. W. So and M. L. Cleary Dimerization: a versatile switch for oncogenesis Blood, August 15, 2004; 104(4): 919 - 922. [Abstract] [Full Text] [PDF]

				J. J.-D. Hsieh, P. Ernst, H. Erdjument-Bromage, P. Tempst, and S. J. Korsmeyer Proteolytic Cleavage of MLL Generates a Complex of N- and C-Terminal Fragments That Confers Protein Stability and Subnuclear Localization Mol. Cell. Biol., January 1, 2003; 23(1): 186 - 194. [Abstract] [Full Text]

				R. T. Luo, C. Lavau, C. Du, F. Simone, P. E. Polak, S. Kawamata, and M. J. Thirman The Elongation Domain of ELL Is Dispensable but Its ELL-Associated Factor 1 Interaction Domain Is Essential for MLL-ELL-Induced Leukemogenesis Mol. Cell. Biol., August 15, 2001; 21(16): 5678 - 5687. [Abstract] [Full Text] [PDF]

				G. S. Stein, M. Montecino, A. J. van Wijnen, J. L. Stein, and J. B. Lian Nuclear Structure-Gene Expression Interrelationships: Implications for Aberrant Gene Expression in Cancer Cancer Res., April 1, 2000; 60(8): 2067 - 2076. [Abstract] [Full Text]

				G. Stein, A. van Wijnen, J. Stein, J. Lian, M Montecino, J Choi, K Zaidi, and A Javed Intranuclear trafficking of transcription factors: implications for biological control J. Cell Sci., January 7, 2000; 113(14): 2527 - 2533. [Abstract] [PDF]

				G. S. STEIN, A. J. VAN WIJNEN, J. L. STEIN, J. B. LIAN, S. H. POCKWINSE, and S. MCNEIL Implications for interrelationships between nuclear architecture and control of gene expression under microgravity conditions FASEB J, May 1, 1999; 13(9001): 157 - 166. [Abstract] [Full Text] [PDF]

				T. de Beer, R. E. Carter, K. E. Lobel-Rice, A. Sorkin, and M. Overduin Structure and Asn-Pro-Phe Binding Pocket of the Eps15 Homology Domain Science, August 28, 1998; 281(5381): 1357 - 1360. [Abstract] [Full Text]

				S. Faderl, H. M. Kantarjian, M. Talpaz, and Z. Estrov Clinical Significance of Cytogenetic Abnormalities in Adult Acute Lymphoblastic Leukemia Blood, June 1, 1998; 91(11): 3995 - 4019. [Full Text] [PDF]

				H. T. Adler, F. S. Nallaseth, G. Walter, and D. C. Tkachuk HRX Leukemic Fusion Proteins Form a Heterocomplex with the Leukemia-associated Protein SET and Protein Phosphatase 2A J. Biol. Chem., November 7, 1997; 272(45): 28407 - 28414. [Abstract] [Full Text] [PDF]