| Written | 2000-02 | Jean-Loup Huret |
| Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France | ||
| Updated | 2006-03 | Marian Stevens-Kroef |
| Clinical Cytogeneticist, UMC St. Radboud, Dept. Human Genetics, Div. Cytogenetics, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands |
| Identity |
| ICD-Topo | C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS |
| ICD-Morpho | 9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS |
| ICD-Morpho | 9920/3 Therapy-related myeloid neoplasms |
| ICD-Morpho | 9989/3 Myelodysplastic syndrome, unclassifiable |
| Atlas_Id | 1186 |
| 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) | |
| 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 |
| 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 | 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 | transcription is from telomere to centromere |
| Protein | 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 | 5'RUNX1- 3'PRDM16 |
| 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. |
| Bibliography |
| A novel syndrome of radiation-associated acute myeloid leukemia involving AML1 gene translocations. |
| Hromas R, Shopnick R, Jumean HG, Bowers C, Varella-Garcia M, Richkind K |
| Blood. 2000 ; 95 (12) : 4011-4013. |
| PMID 10845943 |
| CBFA2(AML1) translocations with novel partner chromosomes in myeloid leukemias: association with prior therapy. |
| Roulston D, Espinosa R 3rd, Nucifora G, Larson RA, Le Beau MM, Rowley JD |
| Blood. 1998 ; 92 (8) : 2879-2885. |
| PMID 9763573 |
| Novel RUNX1-PRDM16 fusion transcripts in a patient with acute myeloid leukemia showing t(1;21)(p36;q22). |
| Sakai I, Tamura T, Narumi H, Uchida N, Yakushijin Y, Hato T, Fujita S, Yasukawa M |
| Genes, chromosomes & cancer. 2005 ; 44 (3) : 265-270. |
| PMID 16015645 |
| 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, Schoenmakers EF, van Kraaij M, Huys E, Vermeulen S, van der Reijden B, van Kessel AG |
| Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2006 ; 20 (6) : 1187-1189. |
| PMID 16598304 |
| Citation |
| This paper should be referenced as such : |
| Stevens-Kroef, M |
| t(1;21)(p36;q22) |
| Atlas Genet Cytogenet Oncol Haematol. 2006;10(3):194-196. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://AtlasGeneticsOncology.org/Anomalies/t0121ID1186.html |
| History of this paper: |
| Huret, JL. t(1;21)(p36;q22). Atlas Genet Cytogenet Oncol Haematol. 2000;4(1):32-32. |
| http://documents.irevues.inist.fr/bitstream/handle/2042/37593/02-2000-t0121ID1186.pdf |
| Other genes implicated (Data extracted from papers in the Atlas) [ 1 ] |
| Genes | RUNX1 |
| Translocations implicated (Data extracted from papers in the Atlas) |
| t(1;21)(p36;q22) RUNX1/PRDM16 | |
| External links |
| REVIEW articles | automatic search in PubMed |
| Last year articles | automatic search in PubMed |
| All articles | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Sun Jul 12 19:45:27 CEST 2020 |
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