| Written | 2009-12 | Jean-Loup Huret, Yongquan Xue |
| Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France (JLH); Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University, Suzhou, PR China (YX) |
| 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 | 9975/3 Chronic myelogenous leukaemia, BCR-ABL1 positive; Myeloproliferative neoplasm, unclassifiable; Myelodysplastic/myeloproliferative neoplasm, unclassifiable |
| ICD-Morpho | 9989/3 Myelodysplastic syndrome, unclassifiable |
| Atlas_Id | 1505 |
| Clinics and Pathology |
| Disease | Myeloid malignancies |
| Epidemiology | Three cases of t(11;21)(q13;q22) in myeloid malignancies are available to date: a 63-year-old female patient with AML evolving from myelodysplastic syndrome (MDS) (Imagama et al., 2007), a 65-year-old male patient with a M2 acute myeloid leukemia (M2-AML) (Dai et al., 2007), and a 70-year-old male patient with a chronic myelogenous leukemia (CML). The t(11;21) was found during transformation into blastic crisis (BC-CML) and in the subsequent reversion to the chronic phase (Wang et al., 1988). |
| Prognosis | The MDS-to-AML case relapsed two years after remission. The M2-AML case died 10 months after diagnosis. The CML case was remaining in remission of blast crisis for 4 months at the time of the report. |
| Cytogenetics |
| Cytogenetics Morphological | The t(11;21) was part of a complex karyotype in the MDS-to-AML case, found with an additional anomaly in the M2-AML case, and accompanying the classical t(9;22)(q34;q11) in the CML case. |
| Genes involved and Proteins |
| Note | The involvement of RUNX1 was proved in the two AML cases; the involvement of MACROD1/LRP16 as the partner of RUNX1 was established in the case described by Imagama et al. |
| Gene Name | MACROD1 (MACRO domain containing 1) |
| Location | 11q13.1 |
| Note | MACROD1 is also known as LRP16 |
| Protein | MACROD1/LRP16 gene has been characterized as an estrogen-responsive gene. LRP16 is required for ERalpha signaling transduction by functioning as an ERalpha coactivator (Han et al., 2007; Han et al., 2008). MACROD1/LRP16-overexpression promotes the cell cycle, and cell proliferation (Yang et al., 2009). |
| Gene Name | RUNX1 (runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene)) |
| Location | 21q22.12 |
| Dna / Rna | Transcription from telomere to centromere. |
| 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 |
| Description | In the case described by Imagama et al. 2007, the translocation fuses RUNX1 exon 5 or exon 6 to MACROD1 exon 2, suggesting that the RUNX1 breakpoint lies in intron 6 and that alternative fusion splice variants are generated. The reciprocal MACROD1-RUNX1 fusion was also detected. |
| 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 |
| Two novel translocations disrupt the RUNX1 gene in acute myeloid leukemia. |
| Dai H, Xue Y, Pan J, Wu Y, Wang Y, Shen J, Zhang J. |
| Cancer Genet Cytogenet. 2007 Sep;177(2):120-4. |
| PMID 17854666 |
| GC-rich promoter elements maximally confers estrogen-induced transactivation of LRP16 gene through ERalpha/Sp1 interaction in MCF-7 cells. |
| Han WD, Si YL, Zhao YL, Li Q, Wu ZQ, Hao HJ, Song HJ. |
| J Steroid Biochem Mol Biol. 2008 Mar;109(1-2):47-56. Epub 2007 Dec 8. |
| PMID 18206366 |
| Estrogenically regulated LRP16 interacts with estrogen receptor alpha and enhances the receptor's transcriptional activity. |
| Han WD, Zhao YL, Meng YG, Zang L, Wu ZQ, Li Q, Si YL, Huang K, Ba JM, Morinaga H, Nomura M, Mu YM. |
| Endocr Relat Cancer. 2007 Sep;14(3):741-53. |
| PMID 17914104 |
| LRP16 is fused to RUNX1 in monocytic leukemia cell line with t(11;21)(q13;q22). |
| Imagama S, Abe A, Suzuki M, Hayakawa F, Katsumi A, Emi N, Kiyoi H, Naoe T. |
| Eur J Haematol. 2007 Jul;79(1):25-31. Epub 2007 May 28. |
| PMID 17532767 |
| A t (11;21) (13;q22) in Ph-positive chronic myelogenous leukemia. |
| Wang TY, Raza A, Sait SN, Stein A, Schumer J, Sandberg AA. |
| Cancer Genet Cytogenet. 1988 Apr;31(2):187-91. |
| PMID 3162392 |
| LRP16 gene function based on bioinformatic analysis. |
| Yang B, Lu XC, Chi XH, Han WD, Yu L, Lou FD. |
| Chin J Cancer. 2009 Dec 5;28(12):1283-90. |
| PMID 19958623 |
| Citation |
| This paper should be referenced as such : |
| Huret, JL ; Xue, Y ; |
| t(11;21)(q13;q22) |
| Atlas Genet Cytogenet Oncol Haematol. 2010;14(10):990-991. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://AtlasGeneticsOncology.org/Anomalies/t1121q13q22ID1505.html |
| Other genes implicated (Data extracted from papers in the Atlas) [ 1 ] |
| Genes | MACROD1 |
| Translocations implicated (Data extracted from papers in the Atlas) |
| t(11;21)(q13;q22) RUNX1/MACROD1 | |
| 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 : Mon Sep 7 15:08:13 CEST 2020 |
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