t(1;21)(p36;q22) RUNX1/PRDM16
2006-03-01 Marian Stevens-Kroef Affiliation1.Clinical Cytogeneticist, UMC St. Radboud, Dept. Human Genetics, Div. Cytogenetics, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands
2.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
Clinics and Pathology
Disease
Acute myeloid leukemia (AML or AML: acute myeloid leukemia) and myelodysplastic syndromes (MDS); 2 of 5 cases at least are secondary to toxic exposure
Note
Only 5 cases described so far one with features identical to a case of , and a case of t(19;21)(q13.4;q22)
Etiology
Two of the reported cases are therapy-related, in another case, AML occurred about 50 years after radiation exposure from nuclear explosions.
Prognosis
poor; median survival 6 months
Cytogenetics
FISH analysis using RUNX1 (red) probe. Three signals for RUNX1 are observed; on the normal chromosome 21, and on the derivative chromosomes 1 and 21.
Additional anomalies
Genes Involved and Proteins
Note
The gene involved in 1p36 is unknown
Gene name
PRDM16 (PR domain containing 16)
Location
1p36.32
Note
This gene is also involved in the t(1;3)(p36;q21) (AML/MDS)
Protein description
Zinc-finger protein, containing two DNA binding domains and a PRDI-BF1 (positive regulatory domain I binding factor 1/ RIZ (retinoblastoma-interacting zinc finger protein) homologous (PR) domain at the N-terminus.
Gene name
RUNX1 (runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene))
Location
21q22.12
Dna rna description
transcription is from telomere to centromere
Protein description
contains a Runt domain and, in the C-term, a transactivation domain; forms heterodimers; widely expressed; nuclear localisation; transcription factor (activator) for various hematopoietic-specific genes
Result of the Chromosomal Anomaly
Note
Two different chimeric transcripts have been identified. One contains the exon 1 to 6 of RUNX1 including the runt domain, fused to sequences derived from intron 1 of PRDM16. The other fusion transcript contains exons 1 to 6 of RUNX1 and almost the entire PRDM16 coding region (see figure below).
Schematic representation of RUNX1 and PRDM16 (fusion) genes.
Upper panel: normal genomic structures of PRDM16 and RUNX1 (non-coding parts in bleu). A cryptic exon, residing within intron 1 of PRDM16, is indicated in green (speckled).
Lower panel: structure of RUNX1-PRDM16 fusion transcripts. Exons are numbered on the basis of consensus gene sequences. Exon sizes are not to scale.
Description
5RUNX1- 3PRDM16
Highly cited references
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 31648321 | 2019 | Transcriptome analysis offers a comprehensive illustration of the genetic background of pediatric acute myeloid leukemia. | 54 |
| 16900497 | 2006 | Overexpression of PRDM16 in the presence and absence of the RUNX1/PRDM16 fusion gene in myeloid leukemias. | 13 |
| 18202228 | 2008 | RUNX1 DNA-binding mutations and RUNX1-PRDM16 cryptic fusions in BCR-ABL+ leukemias are frequently associated with secondary trisomy 21 and may contribute to clonal evolution and imatinib resistance. | 0 |
| 18767145 | 2008 | Cryptic and partial deletions of PRDM16 and RUNX1 without t(1;21)(p36;q22) and/or RUNX1-PRDM16 fusion in a case of progressive chronic myeloid leukemia: a complex chromosomal rearrangement of underestimated frequency in disease progression? | 0 |
| 16015645 | 2005 | Novel RUNX1-PRDM16 fusion transcripts in a patient with acute myeloid leukemia showing t(1;21)(p36;q22). | 0 |
| 16598304 | 2006 | Identification of truncated RUNX1 and RUNX1-PRDM16 fusion transcripts in a case of t(1;21)(p36;q22)-positive therapy-related AML. | 0 |
| 32458418 | 2020 | Complete remission of refractory juvenile acute myeloid leukaemia with RUNX1-PRDM16 in Bloom syndrome after haematopoietic stem cell transplantation. | 0 |
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 10845943 | 2000 | A novel syndrome of radiation-associated acute myeloid leukemia involving AML1 gene translocations. | Hromas R et al |
| 9763573 | 1998 | CBFA2(AML1) translocations with novel partner chromosomes in myeloid leukemias: association with prior therapy. | Roulston D et al |
| 16015645 | 2005 | Novel RUNX1-PRDM16 fusion transcripts in a patient with acute myeloid leukemia showing t(1;21)(p36;q22). | Sakai I et al |
| 16598304 | 2006 | Identification of truncated RUNX1 and RUNX1-PRDM16 fusion transcripts in a case of t(1;21)(p36;q22)-positive therapy-related AML. | Stevens-Kroef MJ et al |
Summary
Fusion gene
RUNX1/PRDM16 RUNX1 (21q22.12) PRDM16 (1p36.32) M t(1;21)(p36;q22)
Note
Subtle cytogenetic abnormality, easy to confuse with a del(21)(q22) , may be missed in poor quality metaphases.
Partial GTG-banded karyotype of t(1;21)(p36;q22)
Citation
Marian Stevens-Kroef
t(1;21)(p36;q22) RUNX1/PRDM16
Atlas Genet Cytogenet Oncol Haematol. 2006-03-01
Online version: http://atlasgeneticsoncology.org/haematological/1186/t(1;21)(p36;q22)-runx1-prdm16
Historical Card
2000-02-01 t(1;21)(p36;q22) RUNX1/PRDM16 by Jean-Loup Huret Affiliation
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
