Claxton D F, Reading C L, Nagarajan L, Tsujimoto Y, Andersson B S, Estey E, Cork A, Huh Y O, Trujillo J, Deisseroth A B
Department of Hematology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Blood. 1992 Aug 1;80(3):582-6.
The chromosomal translocation t(15;17)(q22:21) of acute promyelocytic leukemia (APL) fuses PML, a novel gene, with RAR alpha, a retinoic acid receptor gene. PML-RAR hybrid transcripts were studied in 18 cases of APL using RNA-PCR. Two forms were noted: one designated 5', producing a 439-bp chimeric fragment, and a 3' form, producing a pair of fragments of 765 bp and 909 bp. 5' forms were found in 7 of the 18 cases while the other 11 patients expressed the 3' forms. The chromosome 15 specific probes K3 and K2 were used to study genomic breakpoints in 12 APL patients. Comparison of these results with RNA PCR in 11 patients for whom both were available yielded a rearrangement pattern predictive of whether the hybrid transcript was 5' or 3'. In this way, an additional three patients in whom DNA but not RNA was available were identified as having 3' (downstream) breakpoints and, therefore, 3' hybrid forms. Thus, 21 cases categorized as having 5' or 3' PML-RAR transcripts were analyzed for various phenotypic differences. Surface phenotyping of leukemic promyelocytes demonstrated expression of the CD2 antigen in all cases with the 5' splice variant. Only 1 of 11 cases with the 3' form showed CD2 expression. This difference is significant at P = .001.
急性早幼粒细胞白血病（APL）的染色体易位t(15;17)(q22:21)使一个新基因PML与维甲酸受体基因RARα融合。采用RNA-PCR技术对18例APL患者的PML-RAR杂交转录本进行了研究。发现了两种形式：一种命名为5'型，产生一个439bp的嵌合片段；另一种是3'型，产生一对765bp和909bp的片段。18例患者中有7例为5'型，其余11例患者表达3'型。使用15号染色体特异性探针K3和K2研究了12例APL患者的基因组断点。将这些结果与11例同时进行了RNA PCR检测的患者的结果进行比较，得出了一种重排模式，可预测杂交转录本是5'型还是3'型。通过这种方法，另外3例仅有DNA而无RNA的患者被确定为具有3'（下游）断点，因此为3'杂交形式。因此，对21例归类为具有5'或3' PML-RAR转录本的患者进行了各种表型差异分析。白血病早幼粒细胞的表面表型分析显示，所有5'剪接变体的病例均表达CD2抗原。11例3'型病例中只有1例显示CD2表达。这种差异具有显著性，P = 0.001。
