Study of genetic changes in chronic myeloid leukemia in Vietnam

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。虽然我们观察到越南南部CML患者的生存期（13.1±11.6个月）比越南北部CML患者的生存期（31.5±7.1个月）短得多，但原因尚不清楚。在此，我们报告47例CML患者的细胞遗传学和分子检查结果。细胞遗传学上，44例（93.6%）发生费城（Ph）易位。在其余的Ph（-）型CML患者中，有2例患者表现出BCR/ABL转录本，但没有BCR/ABLFISH融合信号，提示存在2个带有和不带有BCR/ABL融合基因的克隆。令人惊讶的是，在17例（36.2%）患者中（诊断时4例，慢性期11例，加速期2例），我们发现了几种独特的继发染色体异常，包括13三体、部分13三体以及1p、3p、6p、7p、10p和11p异常，这与母细胞期CML观察到的所谓“附加染色体异常”不同。在11例（23.4%）FISH患者中发现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，这表明在疾病进展过程中，一部分患者会发生der(9)缺失。这些观察结果表明，先前存在的遗传不稳定性会诱发各种继发染色体异常和多克隆，导致生存时间缩短。

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.