| Written | 1998-05 | Franck Viguié |
| Laboratoire de Cytogenetique - Service d'Hematologie Biologique, Hopital Hotel-Dieu - 75181 Paris Cedex 04, France |
| 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 |
| Atlas_Id | 1126 |
| Clinics and Pathology |
| Disease | atypical M3 AML (in most cases, M3 AML is characterized by a t(15;17)(q25;q21)) |
| Epidemiology | exceptional (only 1 case fully described), a 6 mth old male patient |
| Clinics | multiple cutaneous localizations; blue-green macules on the scalp and the trunk; coagulation parameters and platelets count were normal |
| Prognosis | complet remission obtained with ATRA treatment and autologous bone marrow transplantation (38 mths disease-free follow up after BMT) |
| Cytogenetics |
| Additional anomalies | no |
| Variants | 3 related translocations observed in M3 AML; the first is the common translocation (15;17) and the two others are extremelly rare; all these translocations involve a breakpoint at 17q21, in RARa, which fuses with different partners: 1- t(15;17)(q22;q21), fusion with PML in 15q22; 2- t(5;17)(q32;q12), fusion with NPM1 in 5q32, encoding for a RNA processing protein; 3- t(11;17)(q23;q21), fusion with PLZF in 11q23, a transcription factor. |
| Genes involved and Proteins |
| Gene Name | NUMA1 (nuclear mitotic apparatus protein 1) |
| Location | 11q13.4 |
| Protein | NuMA protein is an essential component for the formation and maintenance of mitotic spindle poles during mitosis; dimerization domain and nuclear localisation signal. |
| Gene Name | RARA (Retinoic acid receptor, alpha) |
| Location | 17q21.2 |
| Protein | wide expression; nuclear receptor; binds specific DNA sequences: HRE (hormone response elements); ligand and dimerization domain; role in growth and differentiation. |
| Result of the chromosomal anomaly |
| Description | fusion gene on der(11) encompassed by a lamba phage clone B350g; breakpoint in RARa gene in the usual breakpoint cluster region within intron 2. |
| Transcript | 5' NuMA - 3' RARa transcript; no reciprocal 5' RARa - 3' NuMA transcript can be detected |
| Description | 2284 amino acids, 260 kDa; includes the NH2-terminal globular domain and the alpha helical dimerization domain of NuMA (amino acids 1 to 1883) linked to the ligand-binding, dimerization and DNA-binding domains of RARa (amino acids 61 to 462) |
| Expression Localisation | nuclear localisation, under the form of sheet-like nuclear aggregates which partially co-localizes with normal NuMA protein |
| Oncogenesis | as for the three other translocations associated with APL, the main consequence of NuMA-RARa fusion seems to be an alteration in the retinoid signalling pathway; as for PML, PLZF or NPM, NuMA, the forth fusion partner of RARa would " share the capacity to participate in protein-protein interactions, which may result in the formation of abnormal heterodimers or aggregates in which co-activators of retinoid signalling are sequestered " |
| 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 |
| Fusion of retinoic acid receptor alpha to NuMA, the nuclear mitotic apparatus protein, by a variant translocation in acute promyelocytic leukaemia. |
| Wells RA, Catzavelos C, Kamel-Reid S |
| Nature genetics. 1997 ; 17 (1) : 109-113. |
| PMID 9288109 |
| A new variant translocation in acute promyelocytic leukaemia: molecular characterization and clinical correlation. |
| Wells RA, Hummel JL, De Koven A, Zipursky A, Kirby M, Dubé I, Kamel-Reid S |
| Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1996 ; 10 (4) : 735-740. |
| PMID 8618456 |
| Citation |
| This paper should be referenced as such : |
| Viguié, F |
| t(11;17)(q13;q21) |
| Atlas Genet Cytogenet Oncol Haematol. 1998;2(4):132-133. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://AtlasGeneticsOncology.org/Anomalies/t1117ID1126.html |
| Other genes implicated (Data extracted from papers in the Atlas) [ 3 ] |
| Genes | FAU | ZBTB16 | RARA |
| Translocations implicated (Data extracted from papers in the Atlas) |
| t(11;17)(q13;q21) NUMA1/RARA | |
| External links |
| Mitelman database | t(11;17)(q13;q21) [Case List] t(11;17)(q13;q21) [Transloc-MCList] NUMA1/RARA [Fusion-MCList] |
| arrayMap (UZH-SIB Zurich) | Topo ( C42) Morph ( 9861/3) - [auto + random 100 samples .. if exist ] [tabulated segments] |
| Mitelman database | NUMA1/RARA [MCList] NUMA1 (11q13.4) RARA (17q21.2) |
| TICdb | NUMA1/RARA NUMA1 (11q13.4) RARA (17q21.2) |
| 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 : Tue Aug 28 18:17:59 CEST 2018 |
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