Two critical hits for promyelocytic leukemia

被引：110

作者：

He, LZ

Bhaumik, M

Tribioli, C

Rego, EM

Ivins, S

Zelent, A

Pandolfi, PP

机构：

[1] Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Dept Human Genet, New York, NY 10021 USA

[2] Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Program Mol Biol, New York, NY 10021 USA

[3] Inst Canc Res, Leukaemia Res Fund Ctr, Chester Beatty Labs, London SW3 6JB, England

来源：

MOLECULAR CELL | 2000年 / 6卷 / 05期

关键词：

D O I：

10.1016/S1097-2765(00)00111-8

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Acute promyelocytic leukemia (APL) is associated with chromosomal translocations that always involve the RAR alpha gene, which variably fuses to one of several distinct loci, including PML or PLZF (X genes). Due to the reciprocity of the translocation, X-RAR alpha and RAR alpha -X fusion proteins coexist in APL blasts. PLZF-RAR alpha transgenic mice (TM) develop leukemia that lacks the differentiation block at the promyelocytic stage that characterizes APL. We generated TM expressing RAR alpha -PLZF and PLZF-RAR alpha in their promyelocytes. RAR alpha -PUF TM do not develop leukemia. However, PLZF-RAR alpha /RAR alpha -PLZF double TM develop leukemia with classic APL features. We demonstrate that RAR alpha -PLZF can interfere with PLZF transcriptional repression and that this is critical for APL pathogenesis, since leukemias in PLZF(-/-)/PLZF-RAR alpha mutants and in PLZF-RAR alpha /RAR alpha -PLZF TM are indistinguishable. Thus, both products of a cancer-associated translocation are crucial in determining the distinctive features of the disease.

引用

页码：1131 / 1141

页数：11

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