Identification by FISH of 4 novel partner loci of PRDM16 in myeloid malignancies

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11037-11037
Author(s):  
F. Duhoux ◽  
J. Libouton ◽  
K. Bahloula ◽  
G. Ameye ◽  
H. A. Poirel
Keyword(s):  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Gene Encoding ◽  
Bac Contig ◽  
Acute Leukemias ◽  
Myeloid Malignancies ◽  
Artificial Chromosomes ◽  
Functional Studies ◽  
Lymphoid Malignancies ◽  
Pr Domain

11037 Background: PRDM16 is a gene located on 1p36.32 that encodes for a zinc finger transcription factor and contains an N-terminal PR domain. It has been shown to be involved in the reciprocal translocation t(1;3)(p36;q21) and more rarely the t(1;21)(p36;q22) which both occur in myelodysplastic syndromes (MDS) and acute myeloid leukemias (AML). These translocations result in the overexpression of a truncated version of the PRDM16 protein that lacks the PR domain. This overexpression might play an important role in the pathogenesis of MDS and AML in blocking myeloid differentiation. This raises the question whether PRDM16 is rearranged with other partner genes and whether its sequences play the most important role in the oncogenic process attributed to those translocations. Methods: We studied 35 myeloid malignancies, 12 lymphoid malignancies and 3 undifferentiated acute leukemias with 1p36 abnormalities by fluorescent in situ hybridization (FISH) with a bacterial artificial chromosomes (BAC) contig containing 50 BAC probes on 1p36. Results: In addition to the known t(1;3)(p36;q21) (11 cases) and t(1;21)(p36;q22) (1 case) involving RPN1 andAML1/RUNX1 respectively in myeloid malignancies, we specifically found PRDM16 to be rearranged in 4 additional translocations : a t(1;12)(p36;p13) in an AML-M4, a t(1;7)(p36;p12) in a MDS, an add(1)(p36) in an AML-M2 and a t(1;2)(p36;p12) in a relapsed AML-M4. We identified the respective candidate partner loci : TEL/ETV6, IKZF1, CDH4 and a non-coding unknown sequence. Conclusions: In our series of 50 cases of hematological malignancies with 1p36 abnormalities, PRDM16 was involved in about 45% of myeloid malignancies, and was never involved in lymphoid malignancies. PRDM16 is supposed to have similar oncogenic properties as MDS1/EVI-1(3q26), another gene encoding for a zinc finger protein and acting as a transcriptional regulatory factor with 2 isoforms. Interestingly, the shortest isoform of MDS/EVI-1, lacking the PR domain, is supposed to have an oncogenic effect due to its translocation-induced upregulation in AML. Further characterization of these new partner genes and functional studies should give us more insight into the pathogenesis of AML and MDS mediated by PRDM16, and the role of its partner genes. No significant financial relationships to disclose.

scholarly journals Characterization of a Novel Gene Encoding a Putative Single Zinc-finger Protein,ZIM, Expressed during the Reproductive Phase inArabidopsis thaliana

2000 ◽  
Vol 64 (7) ◽  
pp. 1402-1409 ◽  
Author(s):  
Akiko NISHII ◽  
Miho TAKEMURA ◽  
Hidetomo FUJITA ◽  
Masahito SHIKATA ◽  
Akiho YOKOTA ◽  
...  
Keyword(s):  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Gene Encoding ◽  
Novel Gene ◽  
Finger Protein ◽  
Reproductive Phase

scholarly journals Promoter Analysis ofZfp-36,the Mitogen-inducible Gene Encoding the Zinc Finger Protein Tristetraprolin

1995 ◽  
Vol 270 (42) ◽  
pp. 25266-25272 ◽  
Author(s):  
Wi S. Lai ◽  
Michael J. Thompson ◽  
Gregory A. Taylor ◽  
Yi Liu ◽  
Perry J. Blackshear
Keyword(s):  
Zinc Finger ◽  
Promoter Analysis ◽  
Zinc Finger Protein ◽  
Gene Encoding ◽  
Finger Protein ◽  
Inducible Gene

scholarly journals Requirement for the Murine Zinc Finger Protein ZFR in Perigastrulation Growth and Survival

2001 ◽  
Vol 21 (8) ◽  
pp. 2880-2890 ◽  
Author(s):  
Madeleine J. Meagher ◽  
Robert E. Braun
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Cellular Growth ◽  
Gene Encoding ◽  
Growth And Survival ◽  
Finger Protein ◽  
Development Delay ◽  
Cellular Phenotypes

ABSTRACT The transition from preimplantation to postimplantation development leads to the initiation of complex cellular differentiation and morphogenetic movements, a dramatic decrease in cell cycle length, and a commensurate increase in the size of the embryo. Accompanying these changes is the need for the transfer of nutrients from the mother to the embryo and the elaboration of sophisticated genetic networks that monitor genomic integrity and the homeostatic control of cellular growth, differentiation, and programmed cell death. To determine the function of the murine zinc finger protein ZFR in these events, we generated mice carrying a null mutation in the gene encoding it. Homozygous mutant embryos form normal-appearing blastocysts that implant and initiate the process of gastrulation. Mutant embryos form mesoderm but they are delayed in their development and fail to form normal anterior embryonic structures. Loss of ZFR function leads to both an increase in programmed cell death and a decrease in mitotic index, especially in the region of the distal tip of the embryonic ectoderm. Mutant embryos also have an apparent reduction in apical vacuoles in the columnar visceral endoderm cells in the extraembryonic region. Together, these cellular phenotypes lead to a dramatic development delay and embryonic death by 8 to 9 days of gestation, which are independent of p53 function.

scholarly journals Isolation of a gene encoding a functional zinc finger protein homologous to erythroid Krüppel-like factor: identification of a new multigene family.

1995 ◽  
Vol 15 (11) ◽  
pp. 5957-5965 ◽  
Author(s):  
K P Anderson ◽  
C B Kern ◽  
S C Crable ◽  
J B Lingrel
Keyword(s):  
Dna Binding ◽  
Binding Site ◽  
Zinc Finger ◽  
Reporter Gene ◽  
Zinc Finger Protein ◽  
Erythroid Cell ◽  
Specific Gene ◽  
Beta Globin ◽  
Gene Encoding ◽  
Hybridization Probe

We have identified and characterized the gene for a novel zinc finger transcription factor which we have termed lung Krüppel-like factor (LKLF). LKLF was isolated through the use of the zinc finger domain of erythroid Krüppel-like factor (ELKF) as a hybridization probe and is closely related to this erythroid cell-specific gene. LKLF is expressed in a limited number of tissues, with the predominant expression seen in the lungs and spleen. The gene is developmentally controlled, with expression noted in the 7-day embryo followed by a down-regulation at 11 days and subsequent reactivation. A high degree of similarity is noted in the zinc finger regions of LKLF and EKLF. Beyond this domain, the sequences diverge significantly, although the putative transactivation domains for both LKLF and EKLF are proline-rich regions. In the DNA-binding domain, the three zinc finger motifs are so closely conserved that the predicted DNA contact sites are identical, suggesting that both proteins may bind to the same core sequence. This was further suggested by transactivation assays in which mouse fibroblasts were transiently transfected with a human beta-globin reporter gene in the absence and presence of an LKLF cDNA construct. Expression of the LKLF gene activates this human beta-globin promoter containing the CACCC sequence previously shown to be a binding site for EKLF. Mutation of this potential binding site results in a significant reduction in the reporter gene expression. LKLF and EKLF can thus be grouped as members of a unique family of transcription factors which have discrete patterns of expression in different tissues and which appear to recognize the same DNA-binding site.

Gene Encoding a Putative Zinc Finger Protein inSynechocystisPCC6803

1991 ◽  
Vol 55 (9) ◽  
pp. 2259-2264
Author(s):  
Yutaka Ogura ◽  
Tadashi Yoshida ◽  
Yasukazu Nakamura ◽  
Miho Takemura ◽  
Kenji Oda ◽  
...  
Keyword(s):  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Gene Encoding ◽  
Finger Protein ◽  
Putative Zinc Finger
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