골수 호염기구증가 및 형성이상거대핵세포증식과 i(17)(q10)을 단독 세포유전학적 이상으로 가지는 급성골수성백혈병 1예 보고와 문헌 고찰
A Case of Acute Myeloid Leukemia with Bone Marrow Basophilia and Dysmegakaryocytic Hyperplasia with Isochromosome 17q as a Sole Cytogenetic Abnormality: A Clinical Study with Literature Review
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Isochromosome 17q를 단독 세포유전학적 이상으로 가지는 대표적인 혈액종양질환으로는 골수형성이상증후군 및 골수증식종양 등이 있으며 급격한 임상증상의 진행이 특징적이다. 특히, i(17)(q10)을 단독 세포유전학적 이상으로 가지는 골수형성이상증후군은 남성, 심한 빈혈, 형성이상거대핵세포구 증가, 소형거대핵세포구 증가, 호염기구 증가, 호산구 증가 그리고 급성골수성백혈병으로의 높은 이행률을 보이는 것이 특징적이다. 그러나, de novo로발생한 급성골수성백혈병에서 i(17)(q10)을 유일한 세포유전학적이상으로 나타내는 경우는 상대적으로 적어, 이에 대한 임상병리학적 양상 및 분자유전학적 특징이 보고된 바가 드물다. 이에 저자들은 i(17)(q10)을 유일한 세포유전학적 이상으로 동반한 급성골수성백혈병의 본 증례의 임상병리학적 특성 및 마이크로어레이 분석결과를 보고하고자 한다. 본 증례의 특이적인 임상병리적 특징인골수의 호염기구증가, 이상거대핵세포구 증가, 치료에 반응이 없는 임상상 등으로, 잠재된 골수형성이상증후군의 존재를 시사할수 있었다. 본 증례의 i(17)(q10)의 breakpoint는 17p11.2에 위치하였고, 이 부위는 low copy repeats (LCRs)의 특이한 유전적 구조에의해, 유전적 재조합이 잘 일어나는 유전적 불안정 구역으로 알려져 있는 부위였다. 그러므로 i(17)(q10)을 단독 세포유전학적 이상으로 가지는 혈액종양에 있어 17p11.2의 LCRs의 유전적 재조합이특이한 임상병리학적 특징을 결정하고, 암의 발생과 질병의 진행에 영향을 미칠 수 있을 것으로 사료된다.
Abstract
A new clinico-pathological entity in which isochromosome 17q is the sole abnormality has been reported in myelodysplastic syndrome and in myeloproliferative neoplasm with an aggressive course; In particular, myelodysplastic syndrome with the isolated i(17)(q10) chromosome has the unique features of male sex, severe anemia, dysmegakaryocytic hyperplasia, increased micromegakaryocytes, basophilia, eosinophila and high risk for progression to acute myeloid leukemia (AML). However, the isolated i(17)(q10) is occurring at a relatively low frequency in de novo AML, and only a few reports are available in the literature about the clinical features and molecular characteristics of the isolated i(17)(q10) in AML. Herein, we report both the clinico-pathological features and the results of high resolution single nucleotide polymorphism (SNP) array analysis in a case of AML with i(17)(q10) as the sole cytogenetic abnormality. This case showed marrow findings of basophilia and dysmegakaryocytic hyperplasia and aggressive clinical outcome and these findings were suggestive of the presence of underlying myelodysplastic syndrome. The breakpoint of i(17)(q10) was located within 17p11.2 sub-band, which is known as a genetically highly unstable region presenting a unique genomic architectural features of low copy repeats (LCRs); thus, LCRs within 17p11.2 might lead to genomic instability and facilitate somatic genetic rearrangements such as i(17) (q10) and could play an important pathogenetic role in presenting unique clinico-pathologic features as well as in tumor development and disease progression.
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