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급성백혈병의 유전적 이상 검출을 위한 형광제자리부합 프로필 검사의 임상적 유용성

Clinical Utility of Fluorescence in-situ Hybridization Profile Test in Detecting Genetic Aberrations in Acute Leukemia

김희진|김선희|김석란
대한진단검사의학회 (Korean Society For Laboratory Medicine)|2009.10|Annals of Laboratory Medicine|제29권 제5호|pp. 371-378

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키워드

Acute leukemiaCytogenetic analysisFluorescence in-situ hybridization
주제분류병리학

초록

배경 : 급성백혈병에서 유전적 변이는 가장 중요한 예후인자 중 하나이다. 이를 검출하는 방법으로써 통상적인 염색체 검사 에 형광제자리부합 검사를 추가하는 것이 검출의 민감도를 높일 수 있으며, 이때 몇 가지 탐색자들을 프로필화하여 검사하는 것 이 효율적이다. 이에 본 연구는 급성백혈병 환자의 진단 시 시행 된 형광제자리부합 프로필 검사의 유용성에 대해 알아보고자 하였다. 방법 : 2002년 1월부터 2007년 11월까지 삼성서울병원에서 새로 진단된 241명의 급성백혈병 환자를 대상으로 하였다. 급성 림프모구백혈병 프로필에는 BCR/ABL, TEL/AML1, MLL 재배 열 및CDKN2A 유전자 이상을 검사하는 탐색자들이 포함되었으 며 급성 골수성백혈병 프로필로는 AML1/ETO, MLL 및 CBFβ 유전자 이상 검출용 탐색자들을 이용하였다. 환자들의 초진 시의 염색체 검사와 형광제자리부합 프로필 검사 결과를 비교하고, 각각의 검사를 통해 유전적 이상을 밝혀낸 빈도를 조사하였다. 결과 : 급성 림프모구백혈병 형광제자리부합 프로필 검사를 시행한 환자들 중 48.6% (67/138)에서 염색체검사로는 발견하 지 못한 유전적 이상을 발견할 수 있었으며 이 중 37.0% (51/138) 는 염색체 검사상 정상이거나 분열 중인 세포를 확인할 수 없어 핵형 분석이 불가능한 경우였다. 이들 51명의 환자에서 발견된 유전적 이상으로는 TEL/AML1 이상이 44.3%, CDKN2A 이상 이 24.6%를 차지하였고 18%에서 과배수성을 보였다. 급성 골 수성백혈병 형광제자리부합 프로필 검사를 통해서만 유전학적 이상을 발견할 수 있었던 환자들은 7.8% (8/103)이었다. 결론 : 본 연구에서, 급성백혈병의 진단 시 형광제자리부합 프로필 검사를 통해 추가 유전적 변이의 검출률이 유의하게 높 아짐을 확인하였고, 형광제자리부합 프로필 검사는 잠재적 유 전 이상, 복잡 핵형 및 드문 형태의 전위를 검출, 판독하는데 특 히 유용하였다. 따라서, 급성백혈병의 진단 시에는 초진 시에 형 광제자리부합 프로필 검사를 염색체 검사와 함께 시행해야 할 것으로 사료되었다.

Abstract

Background : Cytogenetic abnormalities are one of the most reliable prognostic factors in acute leukemia. Combination of conventional chromosome analysis (CCA) and FISH provides higher sensitivity in detecting these genetic abnormalities, and it is effective to apply several FISH probes as a profile test. The objective of this study was to investigate the utility of FISH profile analyses in the initial diagnosis of acute leukemia. Methods : Two hundred and forty one de novo acute leukemia patients diagnosed from January, 2002 to November, 2007 were included. For acute lymphoblastic leukemia profile test, FISH probes for BCR/ABL, TEL/AML1, MLL gene rearrangement and CDKN2A deletion were used. For acute myeloid leukemia profile test, probes for AML1/ETO, MLL and CBFβgene rearrangement were used. The results of CCA and FISH profile tests were collected, and the positive rates were compared. Results : ALL FISH profile tests revealed additional genetic aberrations not detected by chromosome analysis in 48.6% (67/138) of cases, including those with normal karyotypes or no mitotic cells (37%, 51/138). Among these 51 cases, TEL/AML1 abnormalities were detected in 44.3%, followed by the abnormal CDKN2A signal (24.6%) and hyperdiploidy (18.0%). AML FISH profile tests revealed additional genetic abnormalities in 7.8% (8/103) of cases. Conclusions : FISH analysis as a profile test detected additional genetic aberrations in a significant proportion of acute leukemia, and was effective especially in detecting cryptic translocations, submicroscopic deletions and complex karyotypes. Our study supports the need to incorporate FISH profile test at initial work up in acute leukemia.

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