Study of genetic changes in chronic myeloid leukemia in Vietnam

越南慢性粒细胞白血病基因变化研究

• 批准号: 14571007
• 负责人: SATO Yuko
• 金额: $ 1.79万
• 依托单位: International Medical Center of Japan
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571007/
• 关键词: CML; BCR; ABL; chromosome analysis; FISH; RT-PCR; genetic instability; polymorphism; polymorphism

During the Vietnam War, southern Vietnam was exposed to a large amount of dioxin, a strong human carcinogen. Although we have observed much shorter survival in southern Vietnamese CML patients (13.1±11.6 mo) compared with that of northern Vietnamese CML patients (31.5 ±7.1 mo), the cause remains to be clarified.Here, we report cytogenetic and molecular findings of 47 CML patients. Cytogenetically, the Philadelphia (Ph) translocation was found in 44 (93.6%). Among the remaining patients with Ph(-) CML, 2 exhibited BCR/ABL transcripts but no BCR/ABLFISH fusion signals, suggesting the existence of 2 clones with and without BCR/ABL fusion gene. Surprisingly, in 17 patients (36.2%) (4 at diagnosis, 11 during chronic phase and 2 in accelerated phase), we have found several unique secondary chromosome abnormalities including trisomy 13, partial trisomy 13, and abnormalities of 1p, 3p, 6p, 7p, 10p and 11p, which are different from so-called "additional chromosome abnormalities" observed in blastic phase CML. The Ph translocation with der(9) deletion was found in 11 patients (23.4%) with FISH. Among them, 2 had 2 clones, with and without der(9) deletion, suggesting that der(9) deletion would occur in a subset of patients during disease progression. These observations point to pre-existing genetic instability which would induce various secondary chromosome abnormalities and multiple clones, resulting in shorter survival.

在越南战争期间，越南南部暴露在大量的二恶英中，这是一种强烈的人类致癌物质。尽管我们观察到越南南部CML患者的生存期（13.1±11.6个月）比越南北方CML患者（31.5 ±7.1个月）短得多，但其原因仍有待阐明。细胞遗传学检查发现Ph易位44例（93.6%）。在其余Ph（-）CML患者中，2例有BCR/ABL转录本，但无BCR/ABLFISH融合信号，提示存在BCR/ABL融合基因阳性和阴性2个克隆。令人惊讶的是，在17例患者（36.2%）（4例诊断时，11例慢性期和2例加速期）中，我们发现了几种独特的次级染色体异常，包括13三体，13部分三体，以及1 p，3 p，6p，7 p，10 p和11 p的异常，这与在急变期CML中观察到的所谓“额外染色体异常”不同。11例（23.4%）FISH检测为Ph易位伴der（9）缺失。其中，2例有2个克隆，有和没有der（9）缺失，这表明der（9）缺失将发生在疾病进展期间的患者亚组中。这些观察结果表明，预先存在的遗传不稳定性会诱导各种次级染色体异常和多克隆，导致生存期缩短。

项目成果

Coexistence of Philadelphia-chromosome positive cells with and without der(9) delption in patients with chronic myeloid

慢性粒细胞患者中费城染色体阳性细胞与der(9)缺失的共存

• 发表时间: 2006
• 期刊: Cancer Genet Cytogenet 164
• 作者: Xinh PT;Vu HA;Nghia H;Binh NT;Be TV;Binh TV;Tokunaga K;Sato Y
• 通讯作者: Sato Y

Identification of the breakpoints at ip36.2 and 3p2l.3 in an AML(M3) patient who had t(1;3)(p36.2;p21.3) translocation at the third relapse.

在第三次复发时发生 t(1;3)(p36.2;p21.3) 易位的 AML(M3) 患者中 ip36.2 和 3p2l.3 处断点的识别。

• 发表时间: 2002
• 期刊: Genes Chromosom Cancer 35
• 作者: Tri NK

Xinh PT, Tri NK, Nagao H, Nakazato H, Taketazu F, Fujisawa S, Yagasaki F, Chen YZ, Hayashi Y, Toyoda A, Hattori M, Sakaki Y, Tokunaga K, Sato Y.: "The breakpoints at 1p36.3 detected with BAC/PAC probes in three MDS/AML(M4) patients with t(1;3)(p36;q21) tr

Xinh PT, Tri NK, Nagao H, Nakazato H, Taketazu F, Fujisawa S, Yagasaki F, Chen YZ, Hayashi Y, Toyoda A, Hattori M, Sakaki Y, Tokunaga K, Sato Y.：“1p36.3 处的断点

Izumi H, Hara T, Oga A, Matsuda K, Sato Y, Naito K, Sasaki K: "High telomerase activity. correlates with the stabilities of genome and DNA ploidy in renal cell carcinoma"Neoplasia.. 4. 103-111 (2002)

Izumi H、Hara T、Oga A、Matsuda K、Sato Y、Naito K、Sasaki K：“高端粒酶活性。与肾细胞癌中基因组和 DNA 倍性的稳定性相关”Neoplasia.. 4. 103-111 (2002

t(1;3)(p36;p21) is a recurring therapy-related translocation.

t(1;3)(p36;p21) 是一种反复出现的治疗相关易位。

• 发表时间: 2002
• 期刊: Genes Chromosom Cancer 34
• 作者: Sato Y