细胞遗传学分析在 血液系统恶性肿瘤中的应用 Hwei-Fang Tien, National Taiwan University Hospital

血液系统恶性肿瘤中的重现性染色体异常 识别不同的异常对疾病分类很重要 CML t(9;22) AML t(8;21), t(15;17), inv(16), t(9;11), inv(3), t(6;9), t(1;22), -5/5q-, -7/7q- ALL t(4;11), t(1;19), t(v;11q23), t(12;21)＊ MDS -Y, del(11q); del(5q), del(12p), del(20q); del(7q), +8, +19, i(17q); -7, inv(3) Lymphoma DLBCL t(3q27) Burkitt t(8;14) and variant Follicular t(14;18) Mantle cell t(11;14) Marginal zone t(11;18), t(1;14), t(14;18)

血液系统恶性肿瘤细胞 遗传学研究的目的 诊断和分类 2. 危险因素分层 3. 选择适当的治疗 4. 追踪治疗反应

诊断 病例证实

骨髓涂片， 来自一个患有血小板减少症和贫血的病人 Case 1林順興 NTUH, Gene Chromosome Cancer, 1995,12:161

细胞遗传学异常 最终诊断: 肝脾 Tγ/δ 淋巴瘤 NTUH, Gene Chromosome Cancer, 1995,12:161 The pt received splenectomy. 最终诊断: 肝脾 Tγ/δ 淋巴瘤 NTUH, Gene Chromosome Cancer, 1995,12:161

大颗粒淋巴细胞增多 细胞遗传学异常 外周血涂片 诊断: NK-细胞大颗粒淋巴细胞白血病 Br J Haematol, 1998, 103:1124 Diagnosis: NK-cell large granular lymphocyte leukemia

骨髓涂片，来自一个全血细胞减少症的病人

低增生性 MDS

染色体异常 诊断: 低增生性 MDS Name: 林X榮, 46, XY, -7 [20] Leukemia, 2008, 22:544 2344497 , hypoplastic MDS, 20101129 诊断: 低增生性 MDS Leukemia, 2008, 22:544

淋巴瘤分期 病例证实

骨髓研究用以分期，一个 DLBCL的病人 骨髓涂片 BM biopsy: no lymphoma involvement

魏振良, , 2118776, 201211, DLBCL, BM(+)

淋巴结 骨髓 淋巴结和骨髓中是相同的染色体异常克隆 淋巴瘤侵犯骨髓被证实 淋巴结 骨髓 魏振良, 2118776, 201211, DLBCL, Bone marrow, iliac crest, core biopsy, mild hypocellular marrow with no morphological evidence of lymphoma involvement GROSS FINDING The specimen is a bone marrow fragment, about 1 cm long, received from core biopsy. Submitted in toto, one cassette. MICROSCOPIC FINDING The bone marrow shows mild hypocellularity with hematopoietic components accounting for about 20% of the marrow spaces, and M/E ratio of 2-3:1. Megakaryocytes are adequate in quantity and in morphology. A tiny lymphoid aggregate is noted. CD79a/ CD3(+) cells accounting for about 5% of mononuclear cells without atypical aggregates. Taken together the clinical & hematological features, mild hypocellular marrow with no morphological evidence of lymphoma involvement, is considered. Ref: WBC: 11.33K/μL Hb: 13.7g/dL Platelet: 90K/μL blast: 0% (101/10/17) S1239281 (01). Lymph node, supraclavicular fossa, left, excisional biopsy, malignant lymphoma, diffuse large B-cell L1201037 L1201034 淋巴瘤侵犯骨髓被证实

危险因素分层

AML中细胞遗传学的影响 根据2008年 WHO 分级 5876 patients t(15;17) t(8;21) Inv(16) Normal t(9;11) t(3;5) t(6;9) MDS-related other t(11q23) t(9;22) -7/7q- -5/5q- Inv(3), t(3;3) Medical Research Council , United Kingdom Blood. 2010;116(3):354 , Blood Rev, 2011; 25:39

MDS中的细胞遗传学评分系统 (n=2,754) Schanz et al, J Clin Oncol, 2012 异常 总生存 AML 转化 预后子群 No. of Pts % 单 双 复杂 中位时间 (月) 非常好 81 2.9 del(11q), -Y ― 60.8 NR 好 (参考) 1,809 65.7 Normal, del(5q) del(12p), del(20q) Including del(5q) 48.6 中等 529 19.2 del(7q), +8, i(17q) +19, any other Independent clones Any other 26.0 78.0 差 148 5.4 Inv(3)/t(3q)/del(3q), -7 -7/del(7q) 3 15.8 21.0 非常差 187 6.8 > 3 5.9 8.2 缩写: AML, acute myeloid leukemia; NR, not reached. Schanz et al, J Clin Oncol, 2012

MM: 染色体畸变对总生存的影响 Blood. 2007;109:3489 Figure 2. Impact of genomic aberrations on OS. (A) Kaplan-Meier plot of the impact of del(13) on OS for the 936 patients analyzed for this abnormality. (B) Impact of t(4;14), analyzed in 716 patients. (C) Value of del(17p) on OS of 532 patients. The gray curve is for patients presenting the genomic abnormality, whereas the black curve represents the OS of patients lacking the chromosomal aberration. Blood. 2007;109:3489

CLL中染色体畸变和预后的相关性 13q- sole normal +12 17p- 11q- Prognostic relevance of genomic aberrations in chronic lymphocytic leukemia (CLL).22 Estimated survival probabilities from the date of diagnosis in 325 CLL patients divided into the five categories defined in a hierarchical model of genomic aberrations in CLL. The median survival times for the 17p deletion (n ?23), 11q deletion (n ?56), 12q trisomy (n ?47), normal karyotype (n ?57), and 13q deletion (as single abnormality; n ?117) groups were 32, 79, 114, 111, and 133 months, respectively. 11q- Best Pract Res Clin Haematol. 2007 20:439

追踪临床过程

慢粒，慢性期

CML 急性转化

细胞遗传学研究的作用 不明原因的血细胞减少 不明原因的发热 WHO 对AML和 ALL的分层 MDS 的诊断和分层 (IPSS, IPSS-R) 淋巴瘤的诊断、分层和分期 CLL 和 MM的危险因素分层 追踪治疗反应 Cytopenia, AA vs hypo-MDS Atypical lymphocytosis, reactive? neoplastic

台灣藍鵲（ Formosan Blue Magpie )