Two critical hits for promyelocytic leukemia

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

Research output: Contribution to journalArticle

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Abstract

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
Volume6
Issue number5
StatePublished - 2000
Externally publishedYes

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Acute Promyelocytic Leukemia
Leukemia
Transgenic Mice
Granulocyte Precursor Cells
Genetic Translocation
Genes
Neoplasms
Proteins

ASJC Scopus subject areas

  • Molecular Biology

Cite this

He, L. Z., Bhaumik, M., Tribioli, C., Rego, E. M., Ivins, S., Zelent, A. Z., & Pandolfi, P. P. (2000). Two critical hits for promyelocytic leukemia. Molecular Cell, 6(5), 1131-1141.

Two critical hits for promyelocytic leukemia. / He, Li Zhen; Bhaumik, Mantu; Tribioli, Carla; Rego, Eduardo M.; Ivins, Sarah; Zelent, Arthur Z; Pandolfi, Pier Paolo.

In: Molecular Cell, Vol. 6, No. 5, 2000, p. 1131-1141.

Research output: Contribution to journalArticle

He, LZ, Bhaumik, M, Tribioli, C, Rego, EM, Ivins, S, Zelent, AZ & Pandolfi, PP 2000, 'Two critical hits for promyelocytic leukemia', Molecular Cell, vol. 6, no. 5, pp. 1131-1141.
He LZ, Bhaumik M, Tribioli C, Rego EM, Ivins S, Zelent AZ et al. Two critical hits for promyelocytic leukemia. Molecular Cell. 2000;6(5):1131-1141.
He, Li Zhen ; Bhaumik, Mantu ; Tribioli, Carla ; Rego, Eduardo M. ; Ivins, Sarah ; Zelent, Arthur Z ; Pandolfi, Pier Paolo. / Two critical hits for promyelocytic leukemia. In: Molecular Cell. 2000 ; Vol. 6, No. 5. pp. 1131-1141.
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AU - Zelent, Arthur Z

AU - Pandolfi, Pier Paolo

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