Inaba T, Roberts W M, Shapiro L H, Jolly K W, Raimondi S C, Smith S D, Look A T
Department of Hematology-Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105.
Science. 1992 Jul 24;257(5069):531-4. doi: 10.1126/science.1386162.
A t(17;19) chromosomal translocation in early B-lineage acute leukemia was shown to result in chimeric transcripts that contain sequences from the E2A basic helix-loop-helix transcription factor gene on chromosome 19, fused to sequences from a previously unidentified gene (HLF) on chromosome 17 that encodes a hepatic leukemia factor. The chimeric protein consisted of the amino-terminal transactivation domain of E2A linked to the carboxyl-terminal basic region-leucine zipper domain of HLF. HLF was normally expressed in liver and kidney, but not in lymphoid cells, and was found to be closely related to the leucine zipper-containing transcription factors DBP (albumin D-box binding protein) and TEF (thyrotroph embryonic factor), which regulate developmental stage-specific gene expression.
研究表明,早期B系急性白血病中的t(17;19)染色体易位会导致嵌合转录本的产生,这些转录本包含来自19号染色体上E2A碱性螺旋-环-螺旋转录因子基因的序列,与17号染色体上一个先前未鉴定的基因(HLF)的序列融合,该基因编码肝白血病因子。嵌合蛋白由E2A的氨基末端反式激活结构域与HLF的羧基末端碱性区域-亮氨酸拉链结构域相连组成。HLF通常在肝脏和肾脏中表达,但在淋巴细胞中不表达,并且发现它与含亮氨酸拉链的转录因子DBP(白蛋白D盒结合蛋白)和TEF(促甲状腺素胚胎因子)密切相关,它们调节发育阶段特异性基因表达。