Rearrangement of the breakpoint cluster region and expression of P210 BCR-ABL in a "masked" Philadelphia chromosome-positive acute myeloid leukemia.
Rearrangement of the breakpoint cluster region and expression of P210 BCR-ABL in a "masked" Philadelphia chromosome-positive acute myeloid leukemia.
复制标题
“掩蔽”费城染色体阳性急性髓性白血病中断点簇区域的重排和 P210 BCR-ABL 的表达。
作者：
C. Price;F. Rassool;M. Shivji;J. Gow;C. Tew;C. Haworth;J. Goldman;L. Wiedemann
费城（Ph）易位t（9;22）（q34;q11）常发生于慢性粒细胞白血病（CML），但在急性淋巴细胞白血病（ALL）中不常见，在急性粒细胞白血病（AML）中罕见。在大多数CML病例和部分Ph+ ALL病例中，9 q34的原癌基因ABL易位至22 q11的BCR基因的断点簇区（bcr），形成编码具有增强酪氨酸激酶活性的新型210-kd蛋白（P210 BCR-ABL）的嵌合基因。在其他Ph+ ALL和Ph+ AML患者中，断裂点可能发生在BCR基因的第一个内含子中;这导致编码P190 BCR-ABL. FAB M6的较小嵌合基因。我们研究了1例初发AML患者，该患者具有与广泛核型改变相关的“掩蔽”Ph染色体。白血病细胞最初表现为bcr重排、杂合mRNA的存在和P210 BCR-ABL的表达。这些结果支持BCR-ABL嵌合基因在白血病发生中起关键作用的概念，但表明BCR基因中断点位置以外的因素决定了恶性转化靶细胞的谱系。
The Philadelphia (Ph) translocation t(9;22)(q34;q11) occurs frequently in chronic myeloid leukemia (CML) but is less common in acute lymphoblastic leukemia (ALL) and rare in acute myeloid leukemia (AML). In most cases of CML and some cases of Ph+ ALL the protooncogene ABL from 9q34 is translocated to the breakpoint cluster region (bcr) of the BCR gene at 22q11 to form a chimeric gene encoding a novel 210-kd protein (P210 BCR-ABL) with enhanced tyrosine kinase activity. In other patients with Ph+ ALL and Ph+ AML, the breakpoint probably occurs in the first intron of the BCR gene; this results in a smaller chimeric gene which encodes a P190 BCR-ABL. We studied a patient with AML (FAB M6) arising de novo who had a "masked" Ph chromosome in association with extensive karyotypic changes. The leukemic cells initially showed rearrangement of the bcr, presence of a hybrid mRNA, and expression of the P210 BCR-ABL. These changes were absent in remission. These results support the concept that the BCR-ABL chimeric gene plays a crucial role in leukemogenesis but suggest that factors other than the position of the breakpoint in the BCR gene determine the lineage of the target cell for malignant transformation.