The localization of the HRX/ALL1 protein to specific nuclear subdomains is altered by fusion with its eps15 translocation partner.
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.
Rogaia
D
D
European Institute of Oncology, Department of Experimental Oncology, Milan, Italy.
Grignani
F
F
Carbone
R
R
Riganelli
D
D
LoCoco
F
F
Nakamura
T
T
Croce
C M
CM
Di Fiore
P P
PP
Pelicci
P G
PG
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D019556:COS Cells; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D002451:Cell Compartmentation; D002467:Cell Nucleus / Q000378:metabolism; D002869:Chromosome Aberrations / Q000378:metabolism; D025063:Chromosome Disorders; D002880:Chromosomes, Human, Pair 11; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D019084:Fluorescent Antibody Technique, Indirect; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007938:Leukemia / Q000235:genetics; D051788:Myeloid-Lymphoid Leukemia Protein; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D014157:Transcription Factors; D014162:Transfection; D014178:Translocation, Genetic
D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; C486206:EPS15 protein, human; D047908:Intracellular Signaling Peptides and Proteins; C497422:KMT2A protein, human; D010750:Phosphoproteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase