Tumor associated gene in chromosomal translocation in acute leukemia

急性白血病染色体易位中的肿瘤相关基因

• 批准号: 04454568
• 负责人: HAYASHI Yasuhide
• 金额: $ 3.84万
• 依托单位: University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04454568/
• 关键词: acute leukemia; lymphoma; suppressor gene; translocation; E2A-PBX1; TAL1 gene; MLL gene; TLS; FUS-ERG; 染色体転座; 11q23転座; 癌遺伝子; 切断点近傍遺伝子; AF6遺伝子; 乳児白血病; 遺伝子再構成; 切断点遺伝子; 染色体異常; E2A遺伝子; 分子生物学

E2A-PBX1 chimeric mRNA,which was reported in t (1 ; 19)-acute lymphoblastic leukemia (ALL), was found in 10 of 40 ALL patients. p53 alteration was found in 2 of 20t (1 ; 19)-ALL at diagnosis, 4 of 4 at relapse and 4 of 5 cell lines. We conclude that p53 alteration is associated with relapse or progression. We examined TAL1 alteration in 99 hematological maligmacines and found the alteration in 10 T-ALL patients. Theses patients had similar immunophonotype, normal karyotype, good prognosis, resulting in a subset of T-ALL.TLS/FUS-ERG chimeric mRNA was found in all the 19t (16 ; 21)-acute myeloid leukemia (AML), 18 of whom died. We concluded that t (16 ; 21)-AML patient has a poor prognosis and should be treated by stem cell transplantation in the first remission. MLL gene analysis was preformed on leukemia with 11q23 abnormalities. We found that infant with MLL rearrangements was a poor prognosis. We also found 3 partner genes of MLL gene, AF-5alpha, CBP and p300 gene. We examined the role of these genes in the development of leukemia.

40例急性淋巴细胞白血病（t（1 ; 19）-ALL）患者中10例检测到E2 A-PBX 1嵌合体mRNA。20例t（1 ; 19）-ALL中2例在诊断时、4例在复发时和5例细胞系中4例p53改变。我们的结论是，p53改变与复发或进展。我们检测了99例恶性血液病患者的TAL 1基因，发现10例T-ALL患者存在TAL 1基因的异常。19 t（16 ; 21）急性髓系白血病（AML）患者均检测到TLS/FUS-ERG嵌合体mRNA，其中18例死亡。结论：t（16 ; 21）-AML患者预后差，应在首次缓解期行造血干细胞移植治疗。对11 q23异常的白血病进行MLL基因分析。我们发现MLL重排的婴儿预后不良。我们还发现了MLL基因的3个伴侣基因AF-5 α、CBP和p300基因。我们研究了这些基因在白血病发展中的作用。

项目成果

Shimizu,K.: "An ets-related gene,ERG,is rearranged in human myeloid leukemia with t(16;21)chromosomal translocation." Proc Natl Acad Sci USA. 90. 10280-10284 (1993)

Shimizu, K.：“ET 相关基因 ERG 在人类髓系白血病中通过 t(16;21) 染色体易位进行重排。”

Komuro,H.: "Mutations of the p53 gene are involved in Ewings sarcomas but not in neuroblastomas." Cancer Res. 53. 5284-5288 (1993)

Komuro,H.：“p53 基因突变与尤文氏肉瘤有关，但与神经母细胞瘤无关。”

Tomohiko Taki, Masahiro Sako, Masahiro Tsuchida, and Yasuhide Hayashi: "The t (11 ; 16) (q23 ; p13) Translocation in Myelodysplastic Syndrome Fuses the MLL Gene to the CBP Gene" Blood. Vol 89, No 11 (June 1). 3945-3950 (1997)

Tomohiko Taki、Masahiro Sako、Masahiro Tsuchida 和 Yasuhide Hayashi：“骨髓增生异常综合征中的 t (11 ; 16) (q23 ; p13) 易位将 MLL 基因与 CBP 基因融合”血液。

Kikuchi A.: "Clinical significance of TAL1 gane alteration in childhood T-cell acute lymphoblastic leukemia and lymphoma" Leukemia.

Kikuchi A.：“TAL1 gane 改变在儿童 T 细胞急性淋巴细胞白血病和淋巴瘤中的临床意义”白血病。

Kawamura M,Hayashi Y,Kobayashi S,Kikuchi A et al.: "Mutations of the p53 and ras genes in childhood t(1 ; 19)-acute lymphoblastic leukemia" Blood. 85. 2546-2552 (1995)

Kawamura M、Hayashi Y、Kobayashi S、Kikuchi A 等人：“儿童 t(1 ; 19)-急性淋巴细胞白血病中 p53 和 ras 基因的突变”血液。