Fusion between a novel Krüppel-like zinc finger gene and the retinoic acid receptor-α locus due to a variant t(11;17) translocation associated with acute promyelocytic leukaemia

Zhu Chen, Nigel J. Brand, Alex Chen, Sai Juan Chen, Jian Hua Tong, Zhen Yi Wang, Samuel Waxman, Arthur Z Zelent

Research output: Contribution to journalArticle

560 Citations (Scopus)

Abstract

We have identified a unique case of acute promyelocytic leukaemia (APL) with a t(11;17) reciprocal chromosomal translocation involving the retinoic acid receptor α (RARα) and a previously uncharacterized zinc finger gene. As a result of this translocation, mRNAs containing the coding sequences of the new gene, fused in-frame either upstream of the RARα B region or downstream from the unique A1 and A2 regions of the two major RARα isoforms, are expressed from the rearranged alleles. The above gene, which we have termed PLZF (for promyelocytic leukaemia zinc finger), encodes a potential transcription factor containing nine zinc finger motifs related to the Drosophila gap gene Krüppel and is expressed as at least two isoforms which differ in the sequences encoding the N-terminal region of the protein. Within the haematopoietic system the PLZF mRNAs were detected in the bone marrow, early myeloid cell lines and peripheral blood mononuclear cells, but not in lymphoid cell lines or tissues. In addition, the PLZF mRNA levels were down-regulated in NB-4 and HL-60 promyelocytic cell lines in response to retinoic acid-induced granulocytic differentiation and were very low in mature granulocytes. Our results demonstrate for the first time the association of a variant chromosomal translocation involving the RARα gene with APL, further implicating the RARα in leukaemogenesis and also suggesting an important role for PLZF as well as retinoic acid and its receptors in myeloid maturation.

Original languageEnglish (US)
Pages (from-to)1161-1167
Number of pages7
JournalEMBO Journal
Volume12
Issue number3
StatePublished - 1993
Externally publishedYes

Fingerprint

Acute Promyelocytic Leukemia
Retinoic Acid Receptors
Zinc Fingers
Zinc
Fusion reactions
Genes
Leukemia
Genetic Translocation
Cells
Cell Line
Messenger RNA
Protein Isoforms
Hematopoietic System
HL-60 Cells
Lymphoid Tissue
Myeloid Cells
Tretinoin
varespladib methyl
Granulocytes
Drosophila

Keywords

  • Differentiation
  • Gene expression
  • Haematopoiesis
  • Myeloid

ASJC Scopus subject areas

  • Cell Biology
  • Genetics

Cite this

Fusion between a novel Krüppel-like zinc finger gene and the retinoic acid receptor-α locus due to a variant t(11;17) translocation associated with acute promyelocytic leukaemia. / Chen, Zhu; Brand, Nigel J.; Chen, Alex; Chen, Sai Juan; Tong, Jian Hua; Wang, Zhen Yi; Waxman, Samuel; Zelent, Arthur Z.

In: EMBO Journal, Vol. 12, No. 3, 1993, p. 1161-1167.

Research output: Contribution to journalArticle

Chen, Zhu ; Brand, Nigel J. ; Chen, Alex ; Chen, Sai Juan ; Tong, Jian Hua ; Wang, Zhen Yi ; Waxman, Samuel ; Zelent, Arthur Z. / Fusion between a novel Krüppel-like zinc finger gene and the retinoic acid receptor-α locus due to a variant t(11;17) translocation associated with acute promyelocytic leukaemia. In: EMBO Journal. 1993 ; Vol. 12, No. 3. pp. 1161-1167.
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AU - Chen, Alex

AU - Chen, Sai Juan

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AU - Wang, Zhen Yi

AU - Waxman, Samuel

AU - Zelent, Arthur Z

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