t(1;21)(p36;q22) RUNX1/PRDM16

2006-03-01 Marian Stevens-Kroef Affiliation

1.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

-7, del(7q)

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
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.	20
31648321	2019	Transcriptome analysis offers a comprehensive illustration of the genetic background of pediatric acute myeloid leukemia.	17
16015645	2005	Novel RUNX1-PRDM16 fusion transcripts in a patient with acute myeloid leukemia showing t(1;21)(p36;q22).	16
16598304	2006	Identification of truncated RUNX1 and RUNX1-PRDM16 fusion transcripts in a case of t(1;21)(p36;q22)-positive therapy-related AML.	10
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?	6
16900497	2006	Overexpression of PRDM16 in the presence and absence of the RUNX1/PRDM16 fusion gene in myeloid leukemias.	6
32458418	2020	Complete remission of refractory juvenile acute myeloid leukaemia with RUNX1-PRDM16 in Bloom syndrome after haematopoietic stem cell transplantation.	0

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