SN-1, a novel leukemic cell line with t(11;16)(q23;p13): myeloid characteristics and resistance to retinoids and vitamin D3.
The MLL gene is fused with the cAMP-responsive element binding protein-binding protein (CBP) gene in t(11;16)(q23;p13), which has been reported to be associated with therapy-related acute leukemia. We established a novel myeloid cell line, SN-1, from a patient with T-cell acute lymphoblastic leukemia with t(11;16)(q23;p13) having in-frame MLL-CBP fusion transcripts. The majority of the SN-1 cells were positive for myeloperoxidase when examined using an electron microscope and expressed CD13, CD33, CD56, and HLA-DR antigens, but not CD7, CD10, CD19, CD34, or CD41 antigens, suggesting that these cells are of myeloid origin. SN-1 cells underwent functional and morphological differentiation when treated with actinomycin D or sodium butyrate, but not with all-trans-retinoic acid (ATRA) or 1alpha,25-dihydroxyvitamin D3 (VD3). Exposure of SN-1 cells to ATRA hardly affected cell growth and differentiation, whereas the growth of HL-60 and NB4 cells treated with ATRA was effectively inhibited, and differentiation into mature granulocytes was induced. SN-1 cells were relatively insensitive to VD3 with respect to inhibiting the cell growth and inducing the ability to reduce nitroblue tetrazolium, lysozyme activity, and morphological differentiation, although the expression of CD11b was slightly induced by VD3. These results suggest that the cell line was impaired in the signal transduction systems of ATRA and VD3. This cell line should be useful for the study of the role of CBP as a transcriptional regulator in leukemia differentiation and for the functional analysis of the MLL-CBP fusion gene, which will provide new insights into leukemogenesis caused by 11q23 translocations.
Hayashi
Y
Y
Department of Pediatrics, Faculty of Medicine, University of Tokyo, Japan.
Honma
Y
Y
Niitsu
N
N
Taki
T
T
Bessho
F
F
Sako
M
M
Mori
T
T
Yanagisawa
M
M
Tsuji
K
K
Nakahata
T
T
D000595:Amino Acid Sequence; D001483:Base Sequence; D002675:Child, Preschool; D002762:Cholecalciferol / Q000627:therapeutic use*; D002880:Chromosomes, Human, Pair 11; D002885:Chromosomes, Human, Pair 16; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics; D019008:Drug Resistance, Neoplasm; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D051788:Myeloid-Lymphoid Leukemia Protein; D011519:Proto-Oncogenes; D014157:Transcription Factors; D014178:Translocation, Genetic; D014212:Tretinoin / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D002762:Cholecalciferol; D014212:Tretinoin; D011495:Histone-Lysine N-Methyltransferase