Atlas of Genetics and Cytogenetics in Oncology and Haematology

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

t(X;21)(p22;q22) RUNX1/PRDX4

Written2005-06Yanming Zhang, Janet D Rowley
Cancer Cytogenetics Laboratory, Department of Medicine, Section of Hematology/Oncology, The University of Chicago, 5841 S. Maryland Ave. MC2115, Chicago, IL 60637, USA

(Note : for Links provided by Atlas : click)


ICD-Morpho 9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS
Atlas_Id 1377

Clinics and Pathology

Disease Acute myeloid leukemia with maturation (AML M2) in one case only.
Phenotype / cell stem origin CD13+, CD33+, CD34+, and CD117+ blast population consistent with AML-M2 by FAB subtype.
Etiology Unknown.
Epidemiology Single case involving 74 year old male.
Clinics A 74-year-old Caucasian male patient with progressive weakness and fatigue without any "B symptoms".
Evolution Despite intensive induction chemotherapy with Ara-C, Mitoxantrone, Topotecan and Mylotarg, no remission was obtained. The patient developed prolonged pancytopenia and remained transfusion-dependent.
Prognosis The patient died five months after diagnosis from an episode of febrile neutropenia.

Genes involved and Proteins

Gene NamePRDX4 (peroxiredoxin 4)
Location Xp22.11
Dna / Rna About 24.4 kb in size and contains 7 exons.
Protein PRDX4 is one of six peroxiredoxin-family genes, all of which are highly conserved in eukaryotes and prokaryotes and are ubiquitously expressed, being highest in pancreas, liver, heart and lowest in small intestine, thymus, spleen, and brain, and undetectable in peripheral-blood leukocytes. They use redox-active cysteines to reduce peroxides. In contrast to the intracellular localization of other family members, PRDX4 exists uniquely in the plasma, where the reduced form binds as a homodimer to heparan sulfate on endothelial cell surfaces. PRDXs are also implicated in a number of cellular functions such as cell proliferation and differentiation, enhancement of natural killer cell activity, protection of free radical sensitive proteins, hemoglobin metabolism, and intracellular signaling. PRDX4 plays a regulatory role in the activation of the transcription factor NF-kB by modulating IkB -alpha phosphorylation in the cytoplasm, and thus it is an immediate regulator of H2O2-mediated activation of NF-kB. In addition, PRDX1 or PRDX2 null mice have hemolytic anemia and several malignancies including lymphoma, indicating the essential role of these genes in erythrocyte antioxidant defense and in tumor suppression.
Gene NameRUNX1 (runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene))
Location 21q22.12
Dna / Rna Transcription from telomere to centreomere.
Protein Contains the RUNT binding domain at 5' portion and the transactivation domain at 3' portion. Forms heterodimers; widely expressed; nuclear localization; a transcription factor and critical regulator of hematopoietic-cell development.

Result of the chromosomal anomaly

Hybrid gene
Description AML1 is fused to PRDX4 in-frame. Two in-frame AML1-PRDX4 fusion transcripts were detected with alternative splicing of exon 6 of AML1. One was the fusion between exon 5 of AML1 and exon 2 of PRDX4; the other was between exon 6 of AML1 and PRDX4.
Transcript No PRDX4-AML1 fusion transcript was detected.
Fusion Protein
Description Contains the RUNT binding domain of AML1 at 5' portion and two highly conserved cysteine residue motifs of PRDX4 in 3' portion. The first exon of the PRDX4 gene codes for a signal peptide that allows the secretion of the PRDX4. The first exon is lost as a result of the translocation.
Oncogenesis The hybrid gene could function with a dominant-negative effect on the normal AML1. The hybrid gene contains two cysteine residue motifs of the PRDX4 at the 3' portion, but not the signal peptide which allows the secretion of PRDX4, thus resulting in loss of at least one function of PRDX4 due to non-secretion.
Recently, microarray studies on leukemia samples showed PRDX4 was down-regulated in APL with t(15;17) compared with all other AML samples.

To be noted

Additional cases are needed to delineate the epidemiology of this rare entity:
you are welcome to submit a paper to our new Case Report section.


PRDX4, a member of the peroxiredoxin family, is fused to AML1 (RUNX1) in an acute myeloid leukemia patient with a t(X;21)(p22;q22).
Zhang Y, Emmanuel N, Kamboj G, Chen J, Shurafa M, Van Dyke DL, Wiktor A, Rowley JD
Genes, chromosomes & cancer. 2004 ; 40 (4) : 365-370.
PMID 15188461


This paper should be referenced as such :
Zhang, Y ; Rowley, JD
Atlas Genet Cytogenet Oncol Haematol. 2005;9(4):321-322.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Translocations implicated (Data extracted from papers in the Atlas)

 t(X;21)(p22;q22) RUNX1/PRDX4

External links

Mitelman databaset(X;21)(p22;q22)
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9861/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Mon Dec 14 18:29:35 CET 2020

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us