Hidden FLT3-D835Y clone in FLT3-ITD-positive acute myeloid leukemia that evolved into very late relapse with T-lymphoblastic leukemia
Hidden FLT3-D835Y clone in FLT3-ITD-positive acute myeloid leukemia that evolved into very late relapse with T-lymphoblastic leukemia
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FLT3-ITD 阳性急性髓细胞白血病中隐藏的 FLT3-D835Y 克隆，演变成 T 淋巴细胞白血病晚期复发
DOI：
10.1080/10428194.2017.1382696
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发表时间：
2017
影响因子：
2.6
通讯作者：
Ohyashiki K
中科院分区：
文献类型：
--
作者：
Katagiri S;Umezu T;Asano M;Akahane D;Azuma K;Makishima H;Yoshida K;Watatani Y;Chiba K;Miyano S;Ogawa S;Ohyashiki JH;Ohyashiki K
急性髓性白血病（AML）的晚期复发，在成功治疗后超过5年发生，是罕见的[1，2]。最近，欧洲血液和骨髓移植学会的一项大型回顾性多中心分析表明，自体造血干细胞移植后AML有极晚期复发（> 10年）的可能性[3]。然而，异基因造血干细胞移植（allo-HSCT）后极晚期复发的报道很少[4]。据我们所知，最大的病例系列研究是由Watts等人进行的，报告了3例allo-HSCT后AML极晚期复发的患者，均显示髓外受累[4]。在此，我们报告了一个急性髓单核细胞白血病（AMMoL）与FMS样酪氨酸激酶3（FLT 3-ITD）的内部串联重复突变，谁保持完全缓解（CR）15年后骨髓移植（BMT），但随后复发T淋巴细胞白血病（T-ALL）。鉴于BMT和复发之间的长时间延迟，以及与AMMoL相比复发性疾病的不同表型，我们通过全外显子组测序（WES）和液滴数字聚合酶链反应（ddPCR）分析来分析复发性白血病的起源。我们的研究结果显示，尽管FLT 3-ITD基因消失，但一个携带FLT 3-D835 Y突变的非常小的克隆从AmmoL期开始在T-ALL期扩增。一名46岁男性因呼吸急促被转诊至我院并诊断为AmmoL。血液检查显示白色血细胞（WBC）计数为3.8 x 109/L（原始细胞16%），血红蛋白（Hb）水平为6.2 g/dL，血小板（PLT）计数为156 x 109/L。骨髓（BM）检查显示85.2%的成髓细胞和单核细胞髓过氧化物酶阳性，单核细胞非特异性酯酶阳性。的
Late relapse of acute myeloid leukemia (AML), occurring over five years after successful treatment, is rare [1, 2]. Recently, a large retrospective multicenter analysis from the European Society for Blood and Marrow Transplantation indicated the possibility of very late relapse (> 10 years) of AML after autologous hematopoietic stem cell transplantation [3]. However, there have been few reports of very late relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT)[4]. To our knowledge, the largest case series study was by Watts et al., who reported three patients with very late relapse of AML after allo-HSCT, all of whom showed extramedullary involvement [4]. Herein, we report a patient with acute myelomonocytic leukemia (AMMoL) with internal tandem duplication mutation of FMS-like tyrosine kinase 3 (FLT3-ITD), who maintained complete remission (CR) for 15 years after bone marrow transplantation (BMT) but subsequently relapsed with T-lymphoblastic leukemia (T-ALL). Given the long delay between BMT and relapse, and the different phenotype of the relapsed disease compared with AMMoL, we analyzed the origin of the relapsed leukemia by whole-exome sequencing (WES) and droplet digital polymerase chain reaction (ddPCR) analysis. Our results showed that a very small clone with the FLT3-D835Y mutation from the AMMoL phase expanded in the T-ALL phase, despite the disappearance of FLT3-ITD.A 46-year-old man with shortness of breath was referred to our hospital and diagnosed with AMMoL. Blood tests revealed white blood cell (WBC) count of 3.8 x109/L (with 16% blasts), hemoglobin (Hb) level of 6.2 g/dL and platelet (PLT) count of 156x 109/L. Bone marrow (BM) examination showed 85.2% myeloblasts and monoblasts with positivity for myeloperoxidase, and monoblasts were positive for nonspecific esterase. The
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影响因子：
20.3
作者：
Beekman, Renee;Valkhof, Marijke G.;Touw, Ivo P.
通讯作者：
Touw, Ivo P.
髓外受累对接受 FLAMSA 预处理方案进行 HSCT 的活动性疾病高危 AML 患者的强烈影响
影响因子：
4.8
作者：
Stephan R. Bohl;S. Harsdorf;M. Mulaw;Susanne Hofmann;A. Babiak;C. P. Maier;J. Schnell;L;Katrina Scholl;Verena Wais;R. Schlenk;Lars Bullinger;Mark Ringhoffer;H. Döhner;D. Bunjes;Martin Bommer;F. Kuchenbauer
通讯作者：
F. Kuchenbauer
影响因子：
20.3
作者：
Steensma, David P.;Bejar, Rafael;Ebert, Benjamin L.
通讯作者：
Ebert, Benjamin L.
影响因子：
7.5
作者：
Warren, Mikako;Luthra, Rajyalakshmi;Zuo, Zhuang
通讯作者：
Zuo, Zhuang
极晚期复发（>5年）急性髓性白血病患者的特征和结局
影响因子：
2.6
作者：
B. Medeiros;M. Minden;A. Schuh;A. Schimmer;K. Yee;J. Lipton;H. Messner;Vikas Gupta;K. Chun;W. Xu;P. Das;S. Kamel‐Reid;J. Brandwein
通讯作者：
J. Brandwein