Two critical hits for promyelocytic leukemia

Li Zhen He, Mantu Bhaumik, Carla Tribioli, Eduardo M. Rego, Sarah Ivins, Arthur Zelent, Pier Paolo Pandolfi

Research output: Contribution to journalArticlepeer-review

126 Scopus citations


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

Original languageEnglish (US)
Pages (from-to)1131-1141
Number of pages11
JournalMolecular Cell
Issue number5
StatePublished - 2000
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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