Overexpression of ZNF342 by juxtaposition with MPO promoter/enhancer in the novel translocation t(17;19)(q23;q13.32) in pediatric acute myeloid leukemia and analysis of ZNF342 expression in leukemia

Kathryn S. Poland, Deborah L. Shardy, Mohammed Azim, Rizwan C. Naeem, Robert A. Krance, ZoAnne E. Dreyer, E. Shannon Neeley, Nianxiang Zhang, Hua Qiu Yi, Steven M. Kornblau, Sharon E. Plon

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

We report a novel translocation t(17;19)(q22;q13.32) found in 100% of blast cells from a pediatric acute myeloid leukemia (AML) patient. Fluorescence in situ hybridization and vectorette polymerase chain reaction were used to precisely map the chromosomal breakpoint located on the derivative chromosome 17 at 352 bp 5′ of MPO, encoding myeloperoxidase a highly expressed protein in myeloid cells, and 2,085 bp 50 of ZNF342 on 19q, encoding a transcription factor expressed in human stem cells and previously implicated in mouse models of leukemia. Analysis of RNA levels from the patient sample revealed significant overexpression of ZNF342, potentially contributing to AML formation. This is the first report of a translocation in myeloid leukemia occurring only in the promoter/enhancer regions of the two genes involved, similar to translocations commonly found in lymphoid malignancies. Analysis of ZNF342 protein levels in a large dataset of leukemia samples by reverse phase protein array showed that higher levels of ZNF342 expression in acute lymphoblastic leukemia was associated with poorer outcome (P = 0.033). In the myeloid leukemia samples with the highest ZNF342 expression, there was overrepresentation of FLT3 internal tandem duplication (P = 0.0016) and AML subtype M7 (P = 0.0002). Thus, overexpression of ZNF342 by translocation or other mechanisms contributes to leukemia biology in multiple hematopoietic compartments.

Original languageEnglish (US)
Pages (from-to)480-489
Number of pages10
JournalGenes Chromosomes and Cancer
Volume48
Issue number6
DOIs
StatePublished - Jun 2009
Externally publishedYes

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Acute Myeloid Leukemia
Leukemia
Myeloid Leukemia
Pediatrics
Leukemia, Megakaryoblastic, Acute
Protein Array Analysis
Chromosomes, Human, Pair 17
Myeloid Cells
Fluorescence In Situ Hybridization
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Genetic Promoter Regions
Peroxidase
Proteins
Transcription Factors
Stem Cells
RNA
Polymerase Chain Reaction
Genes
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Medicine(all)

Cite this

Overexpression of ZNF342 by juxtaposition with MPO promoter/enhancer in the novel translocation t(17;19)(q23;q13.32) in pediatric acute myeloid leukemia and analysis of ZNF342 expression in leukemia. / Poland, Kathryn S.; Shardy, Deborah L.; Azim, Mohammed; Naeem, Rizwan C.; Krance, Robert A.; Dreyer, ZoAnne E.; Neeley, E. Shannon; Zhang, Nianxiang; Yi, Hua Qiu; Kornblau, Steven M.; Plon, Sharon E.

In: Genes Chromosomes and Cancer, Vol. 48, No. 6, 06.2009, p. 480-489.

Research output: Contribution to journalArticle

Poland, Kathryn S. ; Shardy, Deborah L. ; Azim, Mohammed ; Naeem, Rizwan C. ; Krance, Robert A. ; Dreyer, ZoAnne E. ; Neeley, E. Shannon ; Zhang, Nianxiang ; Yi, Hua Qiu ; Kornblau, Steven M. ; Plon, Sharon E. / Overexpression of ZNF342 by juxtaposition with MPO promoter/enhancer in the novel translocation t(17;19)(q23;q13.32) in pediatric acute myeloid leukemia and analysis of ZNF342 expression in leukemia. In: Genes Chromosomes and Cancer. 2009 ; Vol. 48, No. 6. pp. 480-489.
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abstract = "We report a novel translocation t(17;19)(q22;q13.32) found in 100{\%} of blast cells from a pediatric acute myeloid leukemia (AML) patient. Fluorescence in situ hybridization and vectorette polymerase chain reaction were used to precisely map the chromosomal breakpoint located on the derivative chromosome 17 at 352 bp 5′ of MPO, encoding myeloperoxidase a highly expressed protein in myeloid cells, and 2,085 bp 50 of ZNF342 on 19q, encoding a transcription factor expressed in human stem cells and previously implicated in mouse models of leukemia. Analysis of RNA levels from the patient sample revealed significant overexpression of ZNF342, potentially contributing to AML formation. This is the first report of a translocation in myeloid leukemia occurring only in the promoter/enhancer regions of the two genes involved, similar to translocations commonly found in lymphoid malignancies. Analysis of ZNF342 protein levels in a large dataset of leukemia samples by reverse phase protein array showed that higher levels of ZNF342 expression in acute lymphoblastic leukemia was associated with poorer outcome (P = 0.033). In the myeloid leukemia samples with the highest ZNF342 expression, there was overrepresentation of FLT3 internal tandem duplication (P = 0.0016) and AML subtype M7 (P = 0.0002). Thus, overexpression of ZNF342 by translocation or other mechanisms contributes to leukemia biology in multiple hematopoietic compartments.",
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AU - Kornblau, Steven M.

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