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白血病之染色體研究現況
Progress in Cytogenetics of the Leukemia
摘要
早在1914年，Theodor Boveri就提出染色體的不正常可導致細胞的惡性變化。直到1950年代以後，關於人類惡性腫瘤的染色體研究因染色體技術的突破與組織培養方法的建立才有劃時代的進展，最具代表的是於慢性骨髓性白血病患者發現費城染色體（Philadelphia chromosome），典型的變化為t（9;22）（q34;q11）；而急性骨髓性白血病之染色體變化因分類有所不同，如M2常見的是t（8;21）（q22;q22）、M3是t（15 ; 17）、M4是第16對染色體不正常、M5是第11對不正常；急性淋巴性白血病常出現的不正常是t（1 ;19）（q23;p13）、t（4;11）（q21;q23）、t（9;22）（q34;q 11）、及del（6q）；慢性淋巴性白血病在B 細胞型態常見trisomy 12、T細胞則以inv（14）（q11q32）出現較多。到了1980 年代，細胞遺傳學與DNA重組技術的合併運用，瞭解了染色體上存有原致癌基因（proto-oncogene），在慢性骨髓性自血病9q34 上之c-abl 輿22q11 上之bcr 相結合，此合成基因之最終產物為210 Kd 之polypeptide，具有tyrosine kinase之活性，在疾病的發展持續上佔有重要角色；在M2之8q22有cmos、21q22有Hu-est-2 M3之15q24-25有c-fes、17q 有c-erbA及neu，M4之16q22有MT cluster，M5之11q23有Hu-ets-1在急性淋巴性白血病之14q23有c-ski、19p13有src、11q23-24 有c-etsl、6q21-24有c-myb；在慢性淋巴性白血病之14q32有控制重鍵免疫球蛋白的基因、14q11有TCR alpha-chain locus、及14q32.3有tcl-l；這些原致癌基因在致癌機轉的角色目前正深入研究之中。由這些不正常染色體及細胞遺傳基因的深入了解，對臨床診斷及預後的評估有著更多的幫助。
並列摘要
Chromosome abnormalities causing the cellular changes from normal to malignant proliferation were first described in 1914 by Theodor Boveri. With the advent of chromosomal banding techniques and the success of tissue culturing methods , the chromosome studies on malignant cells in humankind were established since 19508. The Philadelphia chromosome in patients with chronic myeloid leukemia (CML) was the fir8t consistent chromosome abnormalities. The typical aberration was the reciprocal translocation t(9j22)(q34jqll). A number of specific chromosomal rearrangement had been shown to be associated with particular French-American-British subtypes of the acute myeloid leukemia (AML). The most frequently recurring chromosomal abnormalities were t(8;21) in M2 , t(15;17)in M3 , abnormalities of chromosome 11 in M5. The frequently cytogenetic abnormalities in acute lymphoblastic leukemia (ALL) were t(1;19)(q23;p13) , t(4;11)(q21;q23), t(9;22)(q34;q11) , and del(6q) while in chronic lymphocytic leukemia (CLL) were trisomy 12 in B-cell origin and inv(14)(q11q32) in T-cell origin. During the 1980s, cytogenetics and recombinant DNA technologies had converged to find the proto-oncogene in malignancies. The movement of DNA sequences in CML from 9q34 to 22q11 created a hybrid bcr-abl gene which encodes a 210 Kd polypeptide. The polypeptide had tyrosine kinase activity which mediated the transforming potential of the neoplasia. The proto-oncogenes in AML subtypes were c-mos on 8q22 and H μ-ets-2 on 21q22 in M2, c-fes on 15q24-25 and c-erbA and neu on 17q in M3, MT cluster on 16q22 in M4 , and H μ-ets-l on l1q23 in M5 while in ALL were c-ski on lq23 , src on 19p13, c-ets-1 on 11q23-24, and c-myb on 6q21-24. In CLL of B-cell origin had rearrangements that affected the immunoglobulin heavy-chain locus on 14q32. Whereas those of T-cell origin had changes in TCR alpha-chain locus on 14q11 and tcl-1 on 14q32.3. The leukemogenic mechanism of the proto-oncogenes is in a further research. In parallel with the deepening of basic biological understanding of neoplastic mechanisms, the clinical usefulness of various cytogenetic abnormalities as diagnostic and prognostic aids been increasingly appreciated.